To observe the effects of electroacupuncture at Zusanli (ST36) on the peri-infarct cortex in mice with cerebral ischemia-reperfusion injury, and to explore the key molecular mechanisms underlying the neuroprotective effects of electroacupuncture using transcriptome sequencing. The middle cerebral artery occlusion/reperfusion (MCAO/R) model was established using the filament occlusion method. A total of 30 male C57BL/6 mice were subjected to modeling, and 26 successfully modeled mice were randomly assigned to a model group and an electroacupuncture group, with 13 mice in each group. Nine sham-operated mice were used as controls. From day 1 to day 3 after modeling, electroacupuncture was applied to the Zusanli (ST36) on the affected side using continuous wave stimulation at 15 Hz for 15 min once daily. Neurological deficits were evaluated using the modified neurological severity score (mNSS). Cerebral infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Neuronal morphology and apoptosis in the peri-infarct cortex were examined using Nissl staining and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. Transcriptome sequencing was performed on peri-infarct cortical tissue to identify differentially-expressed genes between the model and electroacupuncture groups, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Key differentially-expressed genes were validated using real-time quantitative polymerase chain reaction (RT-qPCR). Compared with the sham group, the model group showed increased mNSS scores (P<0.01), significantly enlarged infarct volumes (P<0.01), and reduced Nissl bodies in neurons. Compared with the model group, the electroacupuncture group showed reduced mNSS scores and infarct volumes (P<0.01, P<0.05), increased Nissl bodies in peri-infarct neurons, and significantly reduced neuronal apoptosis (P<0.01). A total of 325 differentially-expressed genes were identified in the electroacupuncture group. GO enrichment analysis indicated that these genes were mainly involved in innate immune responses, acute-phase responses, and G protein-coupled receptor binding. KEGG analysis showed enrichment in fat digestion and absorption, complement and coagulation cascades, and platelet activation pathways. Compared with the model group, the mRNA expression levels of interleukin (IL)-6, IL-17, Toll-like receptor 4 (TLR4), and complement component 3 (C3) were significantly decreased in the peri-infarct cortex in the electroacupuncture group (P<0.01 or P<0.05). Electroacupuncture at Zusanli (ST36) significantly improves neurological deficits, reduces infarct volumes, attenuates cortical neuronal injury, and inhibits neuronal apoptosis in MCAO/R mice. The underlying mechanisms may be associated with the regulation of innate immune responses, fat digestion and absorption, and complement and coagulation cascades, manifested as the downregulation of IL-6, IL-17, TLR4, and C3 expression, thereby exerting neuroprotective effects.

AIMS:This multicenter retrospective cohort study aimed to develop 3 predictive models to estimate consciousness status 3 months after admission. These models were designed to serve as complementary prognostic tools for patients diagnosed with unresponsive wakefulness syndrome (UWS) using the Coma Recovery Scale-Revised (CRS-R). METHODS:We retrospectively collected data from 154 patients with UWS across 2 clinical centers, encompassing demographic, clinical, and laboratory biomarkers. Variable selection was performed using adaptive least absolute shrinkage and selection operator (LASSO) and ridge regression. The final predictive models were constructed using binary logistic regression, while additional machine-learning algorithms (Random Forest, SVM, and XGBoost) were applied for comparative evaluations of predictive performance. RESULTS:Of the patients studied, 88 (57%) regained responsiveness within 3 months, while 66 (43%) remained in UWS. Model UWS-base, incorporating clinical factors such as traumatic brain injury (TBI), hypoxic encephalopathy, hydrocephalus, and diffuse injury, demonstrated utility for outpatient preliminary screening. Model UWS-plus achieved superior accuracy (AUC = 0.84) by integrating key biomarkers, including fT3, albumin score, lymphocyte count, and alkaline phosphatase. Model UWS-lite, retaining only lymphocyte count alongside clinical variables, maintained robustness in resource-limited settings (AUC = 0.83). Notably, these biomarkers emerged as factors potentially associated with recovery, generating hypotheses for future interventional studies. CONCLUSION:We propose a biomarker-integrated model that complements the prognosis of UWS. Our findings also encourage a more holistic approach to clinical practice, wherein hydrocephalus management and systemic biomarkers may be considered alongside traditional scales to inform prognosis and guide therapeutic decisions.

OBJECTIVE:To evaluate heart rate variability (HRV) during 75° head-up tilt (HUT) test for differentiating prolonged disorders of consciousness (pDOC) and emergence from minimally conscious state (EMCS). METHODS:A total of 51 participants were enrolled: 18 pDOC patients (7 vegetative state, 11 minimally conscious state), 10 EMCS patients, and 23 healthy controls (HC). Linear HRV metrics were analyzed during supine/tilt positions. Linear Mixed-Effects Models (LMM) were applied to account for repeated measures and other mixed effects. Spearman's correlation was used to examine associations between HRV measures and Coma Recovery Scale-Revised (CRS-R) total scores. RESULTS:LMM including pDOC, EMCS, and HC revealed a significant main effect of time for all HRV indices during the HUT test. Significant group effects were observed for standard deviation of normal-to-normal intervals (SDNN), low frequency (LF), high frequency (HF), and normalized LF (nLF), with HC showing significantly higher SDNN, LF, and HF than pDOC patients. Significant group-by-time interactions were found for proportion of the number of times successive heartbeat intervals exceeded 50 ms divided by the total number of NN intervals, nHF, and LF/HF. Age had a significant negative effect on SDNN, LF, HF, and nLF. In a secondary LMM restricted to pDOC and EMCS patients, significant group effects persisted for SDNN, LF, and HF, with EMCS showing higher values than pDOC; no significant group-by-time interactions were observed. Correlation analyses indicated that tilt-induced LF and SDNN were positively correlated with CRS-R total scores. CONCLUSIONS:pDOC patients demonstrate weaker autonomic responses to postural stimuli than EMCS and HC. SIGNIFICANCE:HUT-based HRV assessment provides a promising and non-invasive tool for pDOC/EMCS differentiation, guiding rehabilitation planning.

While the Coma Recovery Scale-Revised (CRS-R) remains the gold standard for assessing prolonged disorders of consciousness (pDoC), its reliance on overt motor responsiveness and the necessity for repeated assessments to ensure accuracy have driven the clinical search for efficient, motor-independent complementary methods. To address this need, this study investigated the classification value of autonomic responses elicited by standardized Gamma auditory stimulation. In a cohort of 55 pDoC patients (32 UWS/VS and 23 MCS/EMCS), we implemented a concise 10-minute protocol comparing heart rate variability (HRV) between resting state and stimulation-induced conditions. Results demonstrated that while resting-state measurements lacked discriminative capacity, autonomic reactivity triggered by stimulation revealed significant differences. Specifically, MCS/EMCS patients exhibited a distinct pattern of vagal activation (evidenced by decreased heart rate and increased pNN); conversely, UWS/VS patients displayed trends consistent with autonomic rigidity or sympathetic dominance. Classifiers based on these response features (particularly ∆NN50 and ∆pNN) achieved a cross-validated AUROC of 0.71, with the optimal model configuration reaching 0.81. Requiring only standard headphones and a Holter monitor, this method offers rapid, non-invasive, and motor-independent advantages, serving as an effective supplement to the CRS-R.

Accurate differentiation between unresponsive wakefulness syndrome/vegetative state (UWS/VS) and minimally conscious state or emergence from the minimally conscious state (MCS/EMCS) remains clinically challenging in prolonged disorders of consciousness (pDoC), particularly when behavioral responses fluctuate or motor output is limited. We investigated whether short-term heart rate variability (HRV) responses to a standardized 40-Hz auditory perturbation could provide complementary bedside physiological information. Fifty-five patients with pDoC underwent a 10-minute protocol consisting of a 5-minute resting baseline followed by 5 minutes of binaural 40-Hz amplitude-modulated auditory stimulation, with continuous ECG recording. Resting HRV features showed no clear group-level separation between UWS/VS and MCS/EMCS, whereas stimulus-evoked time-domain changes, particularly ΔNN50 and ΔpNN50, differed between groups after false-discovery-rate correction. Exploratory logistic regression models based on NN50- and pNN50-related response features showed measurable internal held-out test performance. These findings suggest that standardized auditory-evoked HRV dynamics may provide a low-burden physiological complement to repeated Coma Recovery Scale-Revised assessment. The results remain exploratory and require validation in larger independent cohorts.

BACKGROUND Chlorfenapyr poisoning is a highly lethal condition that damages high-energy-demand organs such as the central nervous system. Only a few surviving patients have been reported. Survivors may develop focal neurological symptoms, including motor and urinary dysfunction, and the prognosis for these deficits remains unclear. CASE REPORT A 55-year-old man developed chest tightness, profuse sweating, dyskinesia, and paresthesia in both lower limbs, as well as urinary dysfunction, after working for 2 months in a chlorfenapyr production facility. Laboratory toxicology tests confirmed chlorfenapyr and its metabolite in his blood. Magnetic resonance imaging showed diffuse leukoencephalopathy and thoracic cord edema. After repeated detoxification, the patient became clinically stable and was transferred to the Rehabilitation Department of our hospital. Magnetic resonance imaging on admission revealed resolution of central nervous system lesions. After 2 months of pharmacologic treatment, intensive physical therapy, and neuromodulation, the patient progressed from being unable to stand to walking independently, and from indwelling catheterization to voluntary urination. However, abnormal sensations in the lower limbs and excessive sweating showed no significant improvement. CONCLUSIONS This case demonstrates the reversibility of chlorfenapyr-induced leukoencephalopathy and spinal cord lesions. It indicates that chlorfenapyr poisoning-induced motor and urinary dysfunction can be substantially improved through early and multidisciplinary rehabilitation. The persistence of abnormal sensations and sweating suggests that further investigation is required to clarify the underlying mechanisms and optimize management of these symptoms.

Background: This study investigates the reliability of functional near-infrared spectroscopy (fNIRS) in detecting resting-state brain network characteristics in patients with mild cognitive impairment (MCI), focusing on static resting-state functional connectivity (sRSFC) and dynamic resting-state functional connectivity (dRSFC) patterns in MCI patients and healthy controls (HCs) without cognitive impairment. Methods: A total of 89 MCI patients and 83 HCs were characterized using neuropsychological scales. Subject sRSFC strength and dRSFC variability coefficients were evaluated via fNIRS. The study evaluated the feasibility of using fNIRS to measure these connectivity metrics and compared resting-state brain network characteristics between the two groups. Correlations with Montreal Cognitive Assessment (MoCA) scores were also explored. Results: sRSFC strength in homologous brain networks was significantly lower than in heterologous networks (p < 0.05). A significant negative correlation was also observed between sRSFC strength and dRSFC variability at both the group and individual levels (p < 0.001). While sRSFC strength did not differentiate between MCI patients and HCs, the dRSFC variability between the dorsal attention network (DAN) and default mode network (DMN), and between the ventral attention network (VAN) and visual network (VIS), emerged as sensitive biomarkers after false discovery rate correction (p < 0.05). No significant correlation was found between MoCA scores and connectivity measures. Conclusions: fNIRS can be used to study resting-state brain networks, with dRSFC variability being more sensitive than sRSFC strength for discriminating between MCI patients and HCs. The DAN-DMN and VAN-VIS regions were found to be particularly useful for the identification of dRSFC differences between the two groups. Clinical Trial Registration: ChiCTR2200057281, registered on 6 March, 2022; https://www.chictr.org.cn/showproj.html?proj=133808.

Background Cognitive impairment is highly prevalent in people with diabetes. Electroacupuncture improves diabetes-associated cognitive impairment (DACI), but its regulatory mechanism remains unclear. Methods The DACI model was established in rats via high-fat diet combined with low-dose intraperitoneal streptozocin. The acupuncture points Yishu (EX-B3), Zusanli (ST36), and Neiting (ST44) were chosen for electroacupuncture therapy. Cognitive function was assessed by Morris water maze test. Staining with hematoxylin and eosin was used to find the pathological changes in the hippocampus. The expression levels of relative proteins were analyzed by Western blot and immunofluorescence. In addition, ELISA was used to measure the levels of lactate and pyruvate in the hippocampus. Results Electroacupuncture can improve the learning and memory ability of DACI model rats (P<0.01) and hippocampal morphology; electroacupuncture can significantly increase the phosphorylated protein ratios of P-insulin receptor substrates 1 (P-IRS1)/IRS1, P-phosphoinositide 3-kinase (P-PI3K)/PI3K, and P-protein kinase B (P-AKT)/AKT (P < 0.001) and mean fluorescence intensity of P-IRS1, P-PI3K, and P-AKT (P < 0.01); electroacupuncture can promote the expression of glucose transporters (GLUTs) (P < 0.01) and monocarboxylic transporters (MCTs) (P < 0.01) and improves the contents of pyruvate and lactate in the hippocampus of DACI model rats (P < 0.01); Signaling pathway inhibitor LY294002 attenuated the above improvement (P < 0.05). Conclusion Electroacupuncture's mechanism may be involved in activating the IRS1/PI3K/AKT pathway, promoting the expression of GLUTs and MCTs, and regulating hippocampal energy metabolism.

Diagnosing prolonged disorders of consciousness (DoC) remains a significant challenge in neurorehabilitation. Heart rate variability (HRV), a noninvasive measure of cardiac autonomic regulation, has been increasingly recognized as relevant to the mechanisms underlying consciousness. However, long-term HRV data in DoC patients remain scarce. This study aimed to investigate the relationship between long-term HRV metrics and the severity of consciousness impairment in patients with prolonged DoC. In this cross-sectional study, 49 patients with prolonged DoC were enrolled. Each participant underwent five assessments using the Coma Recovery Scale-Revised (CRS-R) and one 24-hour electrocardiographic (ECG) monitoring session within one week of enrollment. Based on their highest CRS-R subscale scores, patients were categorized into three groups: unresponsive wakefulness syndrome (UWS, n = 17), minimally conscious state (MCS, n = 19), and emergence from MCS (EMCS, n = 13). HRV time-domain and frequency-domain indices were extracted from the 24-hour ECG recordings. Differences in HRV metrics among the consciousness groups were analyzed, and correlations between HRV parameters and CRS-R scores were examined. Significant differences in HRV metrics were observed among the three consciousness groups (P < 0.05), including both time-domain indices (SDNN, SDANN, SDNN Index) and frequency-domain indices (HF, LF, VLF, ULF, and Total power). Furthermore, these HRV indices were significantly correlated with CRS-R scores (P < 0.05), indicating a strong association between autonomic function and the level of consciousness. Long-term HRV monitoring reveals significantly greater heart rate variability in EMCS patients compared to those in UWS and MCS, highlighting its potential utility as a supplementary biomarker for assessing consciousness in patients with prolonged DoC.

Objectives: This study aimed to investigate how motor preparation impacted brain activation in individuals with differing cognitive statuses. Methods: We investigated the cortical activation pattern of 57 individuals with mild cognitive impairment (MCI) and 67 healthy controls (HCs) using functional near-infrared spectroscopy (fNIRS) during prepared walking (PW) and single walking (SW) tasks. The study focused on assessing brain activity in four regions of interest (ROIs): the prefrontal cortex (PFC), primary motor cortex, secondary motor cortex, and parietal lobe. Additionally, we examined the behavioral performance—gait speed—during the tasks, analyzed variations in cortical activation intensity, and conducted correlation analyses between Montreal Cognitive Assessment (MoCA) scores, gait speed, and oxygenation levels. Results: There was no significant difference in gait speed between patients with MCI and HCs. The MCI group exhibited lower activation in the primary motor cortex, secondary motor cortex, and parietal regions compared to HCs during the motor execution stage of PW (q < 0.05, FDR-corrected). Additionally, activation in the primary (r = 0.23, p = 0.02) and secondary motor cortices (r = 0.19, p = 0.04) during the motor execution stage of PW correlated significantly with MoCA scores. Furthermore, brain activity in the PFC (r = 0.22, p = 0.02), primary motor cortex (r = 0.22, p = 0.01), secondary motor cortex (r = 0.20, p = 0.02), and parietal lobe (r = 0.19, p = 0.03) during the motor preparation stage of gait was positively correlated with gait speed. Conclusions: Our results revealed that preparing for motor tasks modulated the neural activation patterns of patients with MCI and HCs without affecting their behavioral performance.

The neurovascular unit plays a critical role in maintaining brain structure, function, and homeostasis. Following ischemic stroke, dysfunction and dysregulation of this unit contribute to nerve–blood vessel uncoupling. Intermittent theta-burst stimulation is a repetitive transcranial magnetic stimulation that operates within the theta wave range and can either promote or inhibit cortical excitability. Previous studies have shown that intermittent theta wave stimulation has neuroprotective effects, but the underlying mechanisms remain unclear. In this study, mice subjected to middle cerebral artery occlusion/reperfusion were treated with intermittent theta-burst stimulation. The results showed that intermittent theta-burst stimulation significantly improved neurological function and motor recovery, reduced apoptosis in the peri-infarct region, and activated the PI3K/AKT/GSK3β/β-catenin signaling pathway. Additionally, intermittent theta-burst stimulation suppressed inflammation through the PI3K/AKT/GSK3β and NF-κB pathways. Notably, intermittent theta-burst stimulation strengthened A2 astrocyte–blood vessel coupling, and the effects of intermittent theta-burst stimulation were reversed by the PI3K inhibitor LY294002. These findings demonstrate that intermittent theta-burst stimulation promotes neurovascular unit remodeling and improves neurological outcomes by modulating microglia and astrocytes via the PI3K/AKT/GSK3β and NF-κB signaling pathways.

Objective This study aimed to explore the cumulative effects and expression patterns of electroacupuncture (EA) on irisin secretion, observe the effects of EA on the recovery of neurobehavioral function and vascular remodeling after cerebral ischemia, and elucidate the mechanism by which EA promotes vascular remodeling by regulating irisin expression. Methods A rat model of left middle cerebral artery occlusion (MCAO) was prepared, and EA was performed. Tissue distribution and expression of irisin were determined by immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Western blotting. Type III fibronectin domain protein 5-silenced adeno-associated virus (rAAV-shFNDC5) was injected into the lateral ventricle as a control. Neurobehavioral function was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining and behavioral experiments, while vascular remodeling was evaluated using laser speckle blood flow imaging, and the expressions of irisin and vascular remodeling-related factors were measured by ELISA and Western blotting. Results The number of FNDC5-positive neurons, fluorescence intensity, and irisin expression reached their maximum increase after 7 days of EA treatment. In addition, the EA group exhibited a significant reduction in cerebral infarct volume and impairment of neurobehavioral function, an increase in cerebral blood flow and microvascular diameter on the ischemic side, and significantly higher expression levels of FNDC5, brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), protein kinase B (Akt), and endothelial nitric oxide synthase (eNOS). However, rAAV-shFNDC5 significantly weakened the therapeutic effects of EA. Conclusions EA upregulated irisin expression, reaching a peak after 7 days of EA and then stabilizing. EA facilitated vascular remodeling after cerebral ischemia, and this might be associated with the activation of the irisin-mediated VEGF/Akt/eNOS signaling pathway.

Secondary injuries from ischemia‒reperfusion in stroke, such as edema and hemorrhagic transformation, can significantly impact brain function. This study investigated the effects of intermittent theta burst stimulation (iTBS) on neurological function and cerebral blood flow in a mouse model of ischemia‒reperfusion injury. Laser speckle flowmetry was used to assess changes in cortical blood flow before and after ischemia‒reperfusion. Behavioral assessments were conducted to evaluate motor function recovery. The impact of iTBS on neuronal damage and apoptosis in the peri-infarct area was evaluated via Nissl staining and a TUNEL assay. RNA transcriptome sequencing and immunofluorescence staining were performed to investigate the effects of iTBS on microglial and astrocyte activation and the associated inflammatory response. Our findings demonstrated that iTBS significantly mitigated abnormal perfusion in the infarcted hemisphere, reduced neuronal damage and apoptosis in the peri-infarct area, and enhanced motor function in ischemic mice. Furthermore, iTBS promoted the polarization of microglia and astrocytes toward the anti-inflammatory M2 and A2 phenotypes. Therefore, iTBS provides neurovascular protection by modulating microglial and astrocyte activation and regulating the inflammatory response in the peri-infarct area, thereby improving abnormal cerebral blood flow in both the acute and subacute phases after ischemic brain injury.

Purpose:This study investigated the disparities in brain activation patterns during the Stroop task among individuals with mild cognitive impairment (MCI) and those without any cognitive impairments (healthy controls, HCs) using functional near-infrared spectroscopy (fNIRS). Methods:We analyzed the cortical activation patterns of 73 patients with MCI and 63 HC individuals as they completed the Stroop task, employing fNIRS. The regions of interest (ROIs) included the dorsal prefrontal cortex (dPFC), ventrolateral prefrontal cortex (VLPFC), and parietal lobe (PL). The Stroop task is divided into early stage (0-15 s) and late stage (15-30 s). We also measured participants' behavior during the Stroop task, analyzed variations in cortical activation intensity at different experiment stages, and performed correlation analysis between Montreal Cognitive Assessment (MoCA) scores, Stroop performance, and oxygenation levels. Results:Our analysis revealed that individuals with MCI and HC demonstrated elevated cortical activation in the dPFC, VLPFC, and PL areas while performing the Stroop task (q < 0.05, FDR-corrected). The MCI group displayed longer response latencies compared to the HC group while demonstrating comparable accuracy performance across both congruent and incongruent Stroop trials. The MCI group showed compensatory activation in the VLPFC, and PL regions compared to the HC group during the late stage of the Stroop task (q < 0.05, FDR-corrected). Correlational analysis revealed a negative association between MoCA scores and oxygenation levels in the dPFC, VLPFC, and PL regions during the late stage of the Stroop task (p < 0.05). However, no correlation was found with behavioral performance. Conclusion:Mild cognitive impairment patients demonstrated effective compensation for their cognitive impairments at a partial behavioral level by engaging compensatory activation in the prefrontal, and parietal regions while performing the Stroop task.

Aims: This study aimed to observe the effect of electroacupuncture (EA) at Zusanli point (ST36) on motor function of cerebral ischemia mice, and to observe the effect of EA on mitochondrial morphology of peri-infarct cortex neurons in cerebral ischemia mice. Methods: Middle cerebral artery occlusion (MCAO) was used to develop an ischemic stroke mice model. EA treatment was performed for three consecutive days for 15 min per day after MCAO modeling. We investigated the therapeutic effects of EA on MCAO mice by performing neurobehavioral assessment (modified Neurological Severity Score, Rotarod test, Open-field test and Gait analysis) and TTC staining. The morphology and function of neuronal mitochondria were evaluated by transmission electron microscopy, qRT-PCR, chemiluminescence, and western blot. Nissl staining, TUNEL staining and immunofluorescence staining were used to observe neuronal morphology and apoptosis. Furthermore, ELISA was employed to measure the expression levels of inflammatory factors in mouse serum. Results: EA alleviated motor dysfunction and infarct volume in mice with cerebral ischemia. It improved the neuronal mitochondria damage in MCAO mice, and decreased the protein and mRNA expression level of mitochondrial fission related proteins (FIS1 and Drp1). In addition, EA can reduce neuronal damage and apoptosis of nerve cells, and decrease the level of inflammatory factors (IL-1 beta, TNF-alpha, IL-6 and IL-8) in cerebral ischemia mice. Conclusion: EA therapy can improve motor dysfunction and alleviate the damage of neuron mitochondria in cerebral ischemic mice.

Objective This study aimed to explore the global and future research trends in acupuncture interventions for stroke between 2000 and 2022 using bibliometric analysis. Method A bibliometric analysis of literature from 2000 to 2022 in the Web of Science Core Collection was conducted in this study. The analysis utilized CiteSpace, VOSviewer, and Scimago Graphica software to identify the major contributors to publications, including authors, countries, institutions, journals, references, and keywords. Results The bibliometric analysis yielded a total of 860 publications. There was a gradual increase in the number of publications over the study period. China published the most articles. Evidence-Based Complementary and Alternative Medicine was the journal with the greatest number of publications. The most frequently used keywords were “acupuncture,” “stroke,” and “electroacupuncture.” Conclusion These analysis uncovers the research trends in acupuncture for stroke spanning 2000 to 2022 and points to prospective research frontiers. This study provides a deeper and more thorough understanding of the connotations of acupuncture for stroke and guidance and support for future research in this field.

We report a case of a 39-year-old woman with persistent vegetative state (PVS) following cardiac arrest and a right lower extremity fracture. Despite comprehensive rehabilitation for over 4 months, there was no improvement. Neuroelectrophysiological and neuroimaging assessments showed poor brain function, and the coma recovery scale-revised scale results suggested low arousal probability. Furthermore, patients with PVS exhibit autonomic reactivity and physiological responses to external stimuli. It is important to note that while these reactions may manifest as responsiveness to external stimuli, they should be interpreted as automatic physiological responses rather than indicative of consciousness.

AbstractFew standardized tools are available for evaluation of disorders of consciousness (DOC). The potential of heart rate variability (HRV) during head‐up tilt (HUT) test was investigated as a complementary evaluation tool. Twenty‐one DOC patients and 21 healthy participants were enrolled in this study comparing clinical characteristics and HRV time‐ and frequency‐domain outcomes and temporal changes during HUT test. During the 1st–5th min of the HUT, DOC group showed a significant increase and decrease in log low frequency (LF) (p = 0.045) and log normalized high frequency (nHF) (p = 0.02), respectively, compared to the supine position and had lower log normalized LF (nLF) (p = 0.004) and log ratio of low‐to‐high frequency (LF/HF) (p = 0.001) compared to healthy controls. As the HUT continued from the 6th to the 20th min, DOC group exhibited a significant increase in log LF/HF (16th–20th min) (p < 0.05), along with a decrease in log nHF (6th–10th and 16th–20th min) (p < 0.05) and maintained lower log LF, log nLF, and log LF/HF than controls (p < 0.05). 1st–10th min after returning to the supine position, DOC group demonstrated a significant decrease in log nHF (p < 0.01) and increases in log LF/HF (p < 0.01) and had lower log LF (p < 0.01) and log nLF (p < 0.05) compared to controls. In contrast, the control group exhibited a significant decrease in log nHF (p < 0.05) and increase in log LF/HF (p < 0.05) throughout the entire HUT test. Notably, no significant differences were observed when comparing time‐domain outcomes reflecting parasympathetic nervous system between the two groups. HRV during HUT test indicated a delayed and attenuated autonomic response, particularly in the sympathetic nervous system, in DOC patients compared with healthy individuals.

OBJECTIVE:This study investigates the sleep-modulating effects of ginsenoside Rg1 (Rg1, C42H72O14), a key bioactive component of ginseng, and elucidates its underlying mechanisms. METHODS:C57BL/6J mice were intraperitoneally administered doses of Rg1 ranging from 12.5 to 100 mg/kg. Sleep parameters were assessed to determine the average duration of each sleep stage by monitoring the electrical activity of the brain and muscles. Further, orexin neurons in the lateral hypothalamus (LH) and corticotropin-releasing hormone (CRH) neurons in the paraventricular hypothalamic nucleus (PVH) were ablated using viral vector surgery and electrode embedding. The excitability of LHorexin and PVHCRH neurons was evaluated through the measurement of cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-Fos) expression. RESULTS:Rg1 (12.5-100 mg/kg) augmented the duration of non-rapid eye movement (NREM) sleep phases, while reducing the duration of wakefulness, in a dose dependent manner. The reduced latency from wakefulness to NREM sleep indicates an accelerated sleep initiation time. We found that these sleep-promoting effects were weakened in the LHorexin and PVHCRH neuron ablation groups, and disappeared in the orexin and CRH double-ablation group. Decreased c-Fos protein expression in the LH and PVH confirmed that Rg1 promoted NREM sleep by inhibiting orexin and CRH neurons. CONCLUSION:Rg1 increases the duration of NREM sleep, underscoring the essential roles of LHorexin and PVHCRH neurons in facilitating the sleep-promoting effects of Rg1. Please cite this article as: Wang YY, Wu Y, Yu KW, Xie HY, Gui Y, Chen CR, Wang NH. Ginsenoside Rg1 promotes non-rapid eye movement sleep via inhibition of orexin neurons of the lateral hypothalamus and corticotropin-releasing hormone neurons of the paraventricular hypothalamic nucleus. J Integr Med. 2024; 22(6): 721-730.