Spinal cord injury (SCI) results in permanent motor, sensory, and autonomic dysfunction below the level of injury; currently, there are no effective treatments to promote neural functional recovery. Inflammatory responses, oxidative stress, apoptosis, excitotoxicity, glial scarring, and impaired axonal regeneration-all triggered by secondary damage-are the core pathological mechanisms hindering functional recovery. Traditional drugs, however, are limited by the blood-spinal cord barrier, short half-lives, and systemic toxic side effects, resulting in poor therapeutic efficacy. This article provides a systematic review of research progress over the past decade on the use of nanocarrier-based therapeutics for the treatment of spinal cord injury and analyzes their therapeutic effects through seven major mechanisms, including the inhibition of inflammation and regulation of macrophage/microglia polarization, antagonism of oxidative stress, regulation of programmed cell death and neuroprotection, as well as the promotion of axonal regeneration, myelin repair, glial scar and extracellular matrix remodeling, and vascular repair and blood-spinal cord barrier reconstruction. It further compares the functional characteristics, advantages, and translational potential of major delivery platforms, including liposomes, polymeric nanoparticles, micelles, inorganic nanomaterials, nanozymes, exosomes, biomimetic carriers, nanohydrogels, and composite scaffolds. Among these, biomimetic carriers and multifunctional nanozymes have shown promising preclinical results in trans-barrier delivery and modulation of the injury microenvironment. However, current research still faces bottlenecks such as insufficient long-term safety validation, low targeting efficiency, significant discrepancies between animal models and clinical pathology, and difficulties in scaling up preparation processes. By integrating the characteristics of nanocarriers with the key pathological mechanisms at different stages of spinal cord injury, this paper provides a mechanism-driven analytical framework for the rational design and clinical translation of nanomedicines. In the future, microenvironment-responsive smart delivery, the integration of nanotechnology with stem cells and neuromodulation strategies, and the establishment of standardized evaluation systems may become key directions for advancing the clinical translation of nanomedicines.

Neuroinflammation is a central pathological process in a wide range of central nervous system disorders, yet therapeutic strategies directed solely at single inflammatory targets have shown limited efficacy. Gut-brain axis dysfunction may contribute to neuroinflammatory progression through interconnected metabolic, immune, neural, and vesicle-associated routes. Icariin, a major flavonoid glycoside from Epimedii Folium, has attracted attention because of its anti-inflammatory, neuroprotective, and microbiota-modulating properties. In this review, we summarize current evidence for the anti-neuroinflammatory effects of icariin and explicitly stratify the evidence into three levels: direct icariin-related findings, icariin-related findings without causal gut-brain validation, and mechanisms inferred from broader gut-brain axis biology. Available studies provide relatively stronger support for intestinal barrier protection, microbiota remodeling, peripheral cytokine suppression, and central inflammatory pathway regulation. In contrast, short-chain fatty acid (SCFA)-associated signaling, vagal neuroimmune communication, and extracellular vesicle (EV)-mediated cargo transfer remain plausible but incompletely validated candidate routes. We further compare icariin with its major microbial metabolites, especially icariside II and icaritin, because oral icariin may act partly through metabolite-mediated exposure rather than through robust brain penetration of the parent compound. Major limitations include insufficient causal perturbation, incomplete organ-specific pharmacokinetic data, inter-individual microbiota variability, and uncertain therapeutic time windows. Overall, icariin emerges as a promising multi-target natural product for anti-neuroinflammatory research, but the causal hierarchy and translational relevance of proposed gut-brain pathways require direct validation.

Residual insomnia is the most common residual symptom after remission of depressive disorder and is an important marker for predicting recurrence and insufficient functional rehabilitation. Even when core depressive symptoms improve, difficulty falling asleep, nocturnal awakenings, early morning awakening, and non-restorative sleep may persist, closely linking to anxiety, reduced quality of life, and relapse risk. Thus, residual insomnia should be viewed as a clinical signal that the sleep-mood-circadian system has not yet fully stabilised. Electroacupuncture has been reported to modulate several sleep-related pathways, including the hypothalamic-pituitary-adrenal axis, melatonin secretion, core clock genes, and autonomic activity. However, the current evidence base, mostly derived from animal studies, indirect mechanistic reports, or non-residual-insomnia populations, is insufficient to prove that electroacupuncture reconstructs human circadian rhythms. Most clinical trials rely on subjective scales and lack objective phase markers such as dim-light melatonin onset, cortisol curves, actigraphy, or polysomnography. This article explicitly distinguishes between "subjective sleep improvement" and "objective rhythm reconstruction". We propose a testable research framework that stratifies residual insomnia by circadian phenotypes, uses electroacupuncture as a non-photic time cue, and combines timed intervention to evaluate rhythm-restoring effects. The traditional Midnight-Noon Ebb-Flow (Ziwu Liuzhu) theory is integrated into this chrono-electroacupuncture hypothesis as a heuristic tool for symptom-time recording and protocol design. Future research should adopt rigorous phenotyping, objective circadian biomarkers, and long-term follow-up to advance electroacupuncture from empirical sleep aid towards a precise rhythm-guided intervention.

Background/Objectives: Slow-paced breathing (SPB) is associated with changes in heart rate variability, although these responses are strongly influenced by respiratory patterns; the effects of incorporating an inspiratory breath-hold into an SPB protocol remain insufficiently characterized. This study evaluated the immediate effects of two SPB protocols on heart rate variability (HRV) and cervical pressure pain thresholds (PPT). Methods: A single-blind, randomized, controlled trial was conducted with 60 healthy adults (aged 18-65) stratified by age and sex, and allocated equally (n = 20 per group) to: Protocol 1 (6 s inhalation, 6 s hold, 6 s exhalation), Protocol 2 (6 s inhalation, 6 s exhalation), or a sham control (general respiratory education). Interventions lasted 5 min. Primary outcomes were time-domain HRV indices, root mean square of successive differences (RMSSD) and standard deviation of normal-to-normal (SDNN), recorded using a Polar H10 chest strap. The secondary outcome was PPT at the fourth cervical vertebra (C4) measured via digital algometry. Results: Repeated measures ANOVA revealed a significant time-by-group interaction for heart rate, RMSSD, and SDNN. Both active breathing protocols significantly increased RMSSD and SDNN compared to control, with high effect sizes (η[2]). Notably, Protocol 1 (with inspiratory breath-holding) produced the largest changes in HRV, RMSSD, and SDNN. Conversely, changes in cervical PPT were modest and reached only borderline significance with small effect sizes. Conclusions: Both SPB protocols were associated with acute increases in time-domain HRV indices. Protocol 1 (combining inspiratory breath-holding and lower respiratory frequency) produced a larger acute autonomic response, suggesting its potential utility in non-pharmacological interventions for autonomic dysregulation. However, the isolated contribution of breath-holding cannot be separated from the lower respiratory frequency inherent to this protocol.

Electroacupuncture (EA) is often treated as a uniform intervention, although its central effects vary with electrical parameters and stimulation site. This narrative review, supported by a structured search of PubMed/MEDLINE, Embase, Web of Science Core Collection, China National Knowledge Infrastructure, and SinoMed through August 4, 2026, synthesizes human and animal evidence on how frequency, current intensity, waveform, stimulation duration, and acupoint selection shape regional, network-level, electrophysiological, neurochemical, neurovascular, neuroimmune, and plasticity-related brain responses. Evidence was separated into direct comparative studies and an illustrative subset of single-protocol studies, with complementary transcutaneous electrical acupoint stimulation evidence considered separately. Frequency had the largest and most diverse evidence base. Low-, intermediate-, high-, and alternating-frequency protocols recruited overlapping sensorimotor, insular-cingulate, thalamic, limbic, hypothalamic, midbrain, and medullary systems, but differed in the relative distribution of regional activity and in associated neurochemical, neuronal, neurovascular, and plasticity-related processes. The available heterogeneous evidence does not establish a universally optimal frequency. The smaller current-intensity literature indicates recruitment thresholds, non-linear response ranges, and plateaus. Evidence for waveform and duration is limited and concentrated mainly in animal models of brain injury; waveform comparisons frequently involved concurrent differences in frequency composition and train structure, whereas duration effects varied by model and endpoint. Direct brain-level comparative evidence for pulse width remains insufficient. Acupoint and stimulation-site comparisons further showed site-, laterality-, and point-combination-related differences in cerebral, sensorimotor, neurovascular, and autonomic responses. Single-protocol studies characterized networks, receptors, cell populations, and defined circuits engaged under selected protocols, whereas parameter specificity was assessed from direct comparisons. Collectively, these findings support a multidimensional framework in which electrical dose and acupoint selection jointly shape brain responses. Future studies should use controlled, target-oriented comparisons, report complete stimulation characteristics, and link mechanistic brain measures to clinically relevant outcomes.

Ovarian dysfunction is an important cause of ovulatory disorders, infertility and endocrine disorders in women, which is commonly observed in conditions including polycystic ovary syndrome, primary ovarian insufficiency, diminished ovarian reserve and ovarian aging-related states. Recent studies have demonstrated that besides abnormalities in the classic hypothalamic-pituitary-ovarian axis, autonomic nervous imbalance and immune-inflammatory disturbance also serve as critical mechanisms underlying impaired ovarian function. Central inflammatory responses, chronic stress and metabolic abnormalities can disrupt hypothalamic rhythmic regulation, augment sympathetic nerve output and induce local chronic low-grade ovarian inflammation, consequently contributing to follicular developmental disorders and aberrant steroidogenesis. As a neuromodulation therapy initiated by somatic sensory input, acupuncture can modulate central integration via the "spinal cord-brainstem-hypothalamus" pathway, thereby regulating autonomic nervous activity and immune-inflammatory responses and improving the local ovarian microenvironment. Existing evidence suggests that acupuncture may exert its effects by inhibiting sympathetic overactivation, recruiting vagus-related anti-inflammatory pathways, modulating immune cell polarization, and alleviating oxidative stress and apoptosis. This paper reviews research progress from three aspects: the autonomic-immune regulatory basis of ovarian function, pathological imbalance characteristics, and intervention mechanisms of acupuncture, so as to provide references for neuroimmune-targeted intervention of ovarian dysfunction and acupuncture mechanism research.

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional intestinal disorder characterized by recurrent abdominal pain, diarrhea and altered defecation habits. It is frequently comorbid with psychological disorders such as anxiety and depression, which greatly impair the quality of life. Accumulating evidence demonstrates that the core pathological links of IBS-D involve disrupted brain-gut interaction and dysregulation of the brain-gut "neuro-immune axis", including visceral hypersensitivity, low-grade mucosal inflammation, impaired intestinal barrier function, gut microbiota dysbiosis and abnormal autonomic nerve modulation. Zusanli (ST36) is an essential acupoint for digestive disorders, and the ancient maxim "for abdominal-diseases, Zusanli is indicated" summarizes its prominent clinical value in abdominal ailments. Modern studies have verified that acupuncture at ST36 can remodel vagal-sympathetic balance via the peripheral afferent-central integration-autonomic efferent circuit, modulate central nociceptive and emotional processing, and exert regulatory effects on brain-gut peptide signals such as 5-hydroxytryptamine, suppress immune activation and release of inflammatory mediators, improve the expression of tight-junction proteins and intestinal mucosal permeability, as well as modulate microbiota-metabolite-related pathways. Thereby, it attenuates the neuro-immune feedback of "stress-inflammation-pain amplification", alleviates visceral hypersensitivity and relieves symptoms including abdominal pain and diarrhea. Taking the classical maxim "for abdominal-diseases, Zusanli is indicated" as a clue, this paper reviews research advances regarding acupuncture at ST36 in treating IBS-D by regulating the brain-gut "neuro-immune axis". Limitations of current evidence are also pointed out, including insufficient circuit verification, unclear stimulus parameter-effect relationship and non-standardized clinical protocols, so as to provide references for standardized application and mechanistic exploration of acupuncture at ST36 in treating functional gastrointestinal disorders.

Behavioral, emotional, and cognitive variability across contexts remains insufficiently explained by models that rely on environmental contingencies, cognitive processes, or static trait-based constructs. Individuals may exhibit marked fluctuations in executive functioning, emotional regulation, learning access, behavioral flexibility, and adaptive responses despite retaining knowledge, insight, or previously acquired skills. These patterns are frequently reported in trauma-related conditions, chronic stress, autism spectrum disorder, psychiatric disorders, rehabilitation, and educational settings. ICM 2.0 proposes that these fluctuations reflect dynamic changes in physiological accessibility rather than permanent changes in an individual's underlying capacities. This study operationally defines accessibility as the probability that a previously demonstrated capacity can be recruited under specified physiological, contextual, and task conditions, explicitly distinguishing it from capacity, motivation, engagement, arousal, and performance outcomes. Accessibility is conceptualized as a latent state-dependent construct inferred from converging physiological, behavioral, subjective, and, when available, neural indicators. The Interoceptive Communication Model (ICM 2.0) is proposed as a state-dependent neurophysiological framework that organizes interactions among autonomic regulation, interoceptive processing, affective signaling, sensory load, endocrine activity, immune signaling, environmental context, and higher-order regulatory modulation. The model introduces two broad processing tendencies. Route 1 reflects a limbic-autonomic survival-oriented pattern associated with restricted adaptive accessibility. Meanwhile, Route 2 reflects an insular-prefrontal regulatory pattern associated with expanded adaptive accessibility. These terms are explicitly heuristic and are not intended as anatomical or localized neural pathways. ICM 2.0 generates testable predictions: physiological dysregulation is expected to reduce access to adaptive capacities independently of prior skill acquisition, and regulation-focused interventions are expected to increase accessibility before measurable behavioral improvement from skill training alone. The framework is differentiated from Polyvagal Theory, predictive processing, active inference, and neurovisceral integration. It also specifies measurement strategies, biological mechanisms, and empirical testability criteria.

In recent years, the number of studies on acupuncture intervention for anxiety disorders has been gradually increasing, and its application scope in clinical practice has also been expanding. This article intends to review and discuss the combination of common acupoints, specific operation methods, efficacy evaluation indicators, clinical effects and potential mechanisms of action. Available evidence suggests that acupuncture may influence anxiety-related symptoms through multiple neurobiological pathways, including autonomic regulation, neurotransmitter signaling, neuroendocrine regulation, and neuroplasticity-related mechanisms; however, the causal contribution of individual pathways remains incompletely established. However, there are still some shortcomings in relevant studies, such as limited sample size, lack of uniformity in efficacy criteria, and relatively insufficient follow-up time. Future research should pay more attention to the application of evidence-based medicine methods, strengthen the discussion of mechanisms of action, and try to establish more individualized intervention plans.

Cardiovascular and cerebrovascular diseases (CCVDs) are leading causes of mortality and disability worldwide, and their development is closely linked to bidirectional interactions between the heart and the brain. The heart-brain axis, a systemic framework that integrates neural, humoral, and inflammatory pathways, provides an important theoretical basis for understanding heart-brain comorbidities. With continuous advances in magnetic resonance imaging(MRI), research in this field has progressively shifted from the traditional single-organ diagnostic model to cross-organ and system-oriented strategies for prevention and management. Centered on cardiac magnetic resonance (CMR) and brain MRI, and complemented by quantitative, diffusion, functional, ultra-high-field, and metabolic imaging techniques, multimodal MRI has become a powerful tool for comprehensively characterizing myocardial remodeling, alterations in brain networks, and their coupling relationships. These techniques have been widely applied in studies of representative heart-brain comorbidities, including cardiac dysfunction associated with acute brain injury, cognitive impairment related to heart failure, and cardiovascular abnormalities associated with neurodegenerative diseases, such as Alzheimer's disease (AD). Such studies have not only revealed structural and functional alterations in the heart and brain but have also provided important insights into potential mechanisms, including autonomic imbalance, neuroendocrine activation, and inflammatory responses. However, current heart-brain axis research remains largely based on correlational analyses, whereas causal inference and characterization of dynamic mechanisms remain insufficient. In addition, significant challenges persist in multimodal data integration and clinical translation. Overall, MRI is driving heart-brain axis research from structural characterization toward mechanistic investigation. In the future, integrating imaging, physiological, and genetic information may enable early identification, risk stratification, and precision intervention for heart-brain comorbidities, thereby promoting a transition in medical practice from single-organ management to systemic prevention and treatment.