Dietary Behavior, Physical Activity, and 24-Hour Rhythm Coherence: A Digital Phenotyping Perspective on Vascular and Glycemic Health.

Sepsis is no longer conceptualized as a simple systemic inflammatory response. The Sepsis-3 definition emphasizes life-threatening organ dysfunction caused by a dysregulated host response to infection (). Global estimates indicate that sepsis contributed to approximately 48.9 million cases and 11.0 million sepsis-related deaths in 2017, corresponding to nearly one fifth of all global deaths (). Contemporary international guidelines prioritize time-sensitive antimicrobial therapy, source control, hemodynamic optimization, vasopressor support, corticosteroids in selected shock phenotypes, mechanical ventilation, renal replacement therapy, nutrition, and other organ-support strategies (). These measures remain the therapeutic foundation of sepsis care. Nevertheless, sepsis-associated organ dysfunction frequently progresses despite technically adequate source control and hemodynamic support. One explanation is that sepsis is immunologically dynamic. Early inflammatory amplification, endothelial activation, complement and coagulation dysregulation, mitochondrial dysfunction, lymphocyte apoptosis, impaired antigen presentation, and macrophage exhaustion may overlap within the same patient (, ). This complexity has undermined many single-target anti-inflammatory and immunostimulatory strategies. A rational adjunctive therapy would therefore need to be titratable, context-sensitive, and less likely to abolish host antimicrobial defense. Acupuncture has historically been used in inflammatory and gastrointestinal disorders. Bioelectronic medicine and neuroimmunology provide a mechanistic framework for understanding how peripheral neural stimulation may influence immune responses (). The anatomical discovery of hardwired neuroimmune circuits, such as the vagal-splenic axis and the cholinergic anti-inflammatory reflex, demonstrates that the central nervous system continuously monitors and intricately calibrates peripheral innate immunity (, ). Within this framework, electroacupuncture (EA) can be viewed as a reproducible form of somatosensory electrical stimulation rather than as a conventional anti-infective therapy. By applying precise electrical parameters to specific peripheral somatosensory coordinates (), EA may engage autonomic and neuroendocrine reflexes that modulate inflammatory responses in experimental settings. This allows for the precise, dose-dependent dampening of localized hyperinflammation and the preservation of critical organ barriers, circumventing the systemic toxicity of conventional pharmacological agents (). Recent reviews have summarized the anti-inflammatory and organ-protective effects of EA in sepsis, including a systematic review of excessive inflammatory responses and organ damage () and a 2025 rodent-literature review focused on ST36-mediated neuro-endocrine-immune regulation, exosome biology, and multi-organ protection (). A previous ST36-focused systematic review of experimental sepsis also highlighted substantial laboratory evidence but emphasized methodological heterogeneity and limited translatability (). Therefore, the present review shifts the focus from whether EA is biologically plausible to how it should be critically evaluated, safely implemented, and rigorously tested as an adjunctive neuroimmune intervention in sepsis. We integrate selected concepts from newer mechanism-oriented literature, including local acupoint biology, afferent recruitment, gut microbiota-metabolite axes, and stimulation-dose standardization, while deliberately avoiding overextension from non-sepsis EA fields. The central argument is that EA can be considered only as an adjunct to guideline-based sepsis care and that its potential clinical value should be tested through ICU-compatible, phenotype-specific, sham-controlled trials with organ-specific endpoints and robust safety governance. As illustrated in , sepsis-associated organ dysfunction arises from reciprocal interactions among innate immune activation, autonomic imbalance, endothelial-microvascular injury, barrier failure, and mitochondrial-metabolic dysfunction.