Interactions among tumors, nerves, and immune cells influence cancer progression, but the mechanisms coordinating these compartments remain incompletely understood. Bioelectric signaling has been proposed as an additional coordinating layer, yet direct in vivo evidence for a tumor–nerve–immune electrical axis remains limited. In non-tumor models, RUSH3D-HR enables mesoscale in vivo imaging of dynamic cellular behaviors, including neutrophil swarming and migrasome dynamics, and has revealed reduced splenic neutrophil swarming following electroacupuncture at Zusanli (ST36). These observations provide dynamic cellular readouts and demonstrate an intervention-associated response; however, the platform does not directly measure membrane voltage, ionic currents, or electric fields, and these findings establish neither electrical coupling nor a specific neural circuit. In this mini review, we examine the proposed axis as a focused, falsifiable complement to broader cancer neuroscience. We distinguish direct observations from mechanistic hypotheses, consider established biochemical explanations involving neurotransmitters and inflammatory mediators, and discuss how context-dependent neural effects, supporting glial cells, opioids, and cancer-induced nerve injury may modify tumor–nerve–immune interactions. We then outline a staged experimental roadmap in tumor models, integrating RUSH3D-HR with voltage and ion reporters, extracellular electrophysiological recordings, and compartment-specific perturbations. This framework prioritizes temporal relationships, identification of candidate signal sources and responding compartments, and causal tests that discriminate electrical contributions from biochemical and systemic effects. Establishing reproducible links between electrical measurements, cellular behavior, and tumor outcomes will be essential for evaluating the axis. Until such evidence is obtained, the tumor–nerve–immune electrical axis should be regarded as a hypothesis-generating experimental program rather than a validated physiological circuit.

Colorectal diseases pose a serious threat to human health, and conventional endoscopy has limitations in lesion characterization. This consensus aims to clarify the indications, operational specifications, image interpretation criteria, and quality control requirements for probe-based confocal laser endomicroscopy (pCLE) in lower gastrointestinal diseases, particularly colorectal cancer, precancerous lesions and polyps, and inflammatory bowel disease (IBD). A systematic literature search covered PubMed, Embase, the Cochrane Library, CNKI, and Wanfang Database through August 2026. Evidence was graded using the Grading of Recommendations Assessment, Development and Evaluation system. Forty-eight experts participated in two rounds of discussion and online voting, with agreement ≥80% required for consensus. Eight recommendations were finalized: five strong and three weak. Strong recommendations address colorectal lesion differentiation, targeted biopsy, mucosal barrier assessment, ulcerative colitis mucosal healing and relapse prediction, and IBD-associated colorectal neoplasia surveillance. Weak recommendations address distal resection margin assessment during radical surgery for low rectal cancer, irritable bowel syndrome research, and adjunctive IBD diagnosis and differentiation. Evidence for endoscopic resection margin assessment remains insufficient, and pCLE is not recommended for routine diagnosis of irritable bowel syndrome. pCLE provides adjunctive microscopic information for colorectal lesion characterization, targeted biopsy, and IBD assessment and surveillance; in IBD diagnosis, it does not replace conventional endoscopic and histopathological evaluation. This consensus provides evidence-based guidance for standardized clinical application.

Human serum albumin (HSA) is a multifunctional carrier protein that helps maintain vascular barrier integrity and intravascular fluid homeostasis and has long been used in the management of critically ill patients, including those with acute brain injury. HSA is thought to exert neuroprotective effects through four complementary mechanisms: oncotic/volume expansion and hemodilution, antioxidant and anti-inflammatory effects, HSA-nitric oxide-mediated antithrombotic activity, and glycocalyx stabilization, although the precise pathways remain incompletely understood. Despite its biological rationale, the clinical efficacy of HSA in severe neurological disorders remains inconclusive, and few guidelines provide specific recommendations for its use in neurological care. This uncertainty stems primarily from the complex etiology and heterogeneous pathophysiology of neurological disorders, as well as inconsistent findings across existing studies. This narrative review aims to summarize the current evidence on HSA use in traumatic brain injury, acute ischemic stroke, and aneurysmal subarachnoid hemorrhage, identify existing knowledge gaps, and provide insights for future research and clinical practice. We screened records from PubMed, Embase, the Cochrane Library, CNKI, and Yiigle, as well as ClinicalTrials.gov, ChiCTR, and ChinaDrugTrials. A total of 29 human and animal studies were included. Collectively, available evidence supports a biological rationale for HSA therapy in neurocritical care, yet its clinical benefit remains incompletely established and substantial challenges persist. Prospective randomized controlled trials are warranted to clarify the efficacy and safety of HSA and determine whether preliminary encouraging findings can inform standardized guidelines and expert consensus recommendations, particularly regarding optimal concentration, timing, and patient selection.

CRKL is a non-catalytic Src homology 2 (SH2)/Src homology 3 (SH3)-domain adaptor protein implicated as an oncogenic driver across a wide range of human malignancies, yet existing literature is fragmented across tumor-type-specific studies of uneven evidentiary strength; evidence for CRKL is often conflated with studies of its paralog Crk, and directly conflicting functional findings in at least one cancer type remain unreconciled. This review synthesizes CRKL’s structure and signaling mechanism across ten cancer types: breast, hepatocellular, non-small-cell lung, pancreatic, ovarian, gastric, laryngeal squamous cell, and colorectal carcinoma, cutaneous melanoma, and chronic myeloid leukemia (CML), framed against the Insulin Receptor Substrate (IRS) family as a conceptual precedent for adaptor-protein oncogenesis. In several solid tumors reviewed, CRKL overexpression or amplification shows a recurring signaling framework involving SH2-mediated docking onto activated oncoproteins coupled through its SH3 domains to C3G, SOS1, and DOCK180, driving RAS/RAP1-ERK signaling, proliferation, and MMP2/MMP9-dependent invasion, with overexpression generally associated with advanced stage and reduced survival. Hepatocellular carcinoma is a documented exception, where human-tissue and murine cell-line studies report opposing functional directions for CRKL. Evidentiary strength varies substantially across cancers: CML has the strongest translational evidence, with phosphorylated CRKL used as a pharmacodynamic biomarker of BCR-ABL kinase inhibition in clinical-trial and research settings, distinct from routine BCR::ABL1 monitoring; most solid tumors are supported by preclinical amplification, expression, and knockdown data; and immune-related associations with CRKL have been reported in melanoma, while a direct immune-evasion mechanism has been demonstrated in hepatocellular carcinoma; these relationships remain largely unexamined elsewhere. This review identifies concrete research gaps, including the unresolved CRKL-Crk relationship and the largely unpursued opportunity to target CRKL’s SH2/SH3 interfaces therapeutically. Overall, CRKL emerges as a recurrently implicated oncogenic adaptor with strong mechanistic and translational support in selected settings, most notably CML, and a rational candidate for future drug discovery, rather than an already-established pan-cancer therapeutic target.

Traumatic brain injury, spinal cord injury, and ischemic stroke share secondary pathological processes that may persist beyond the acute insult. Cellular senescence and senescence-like states may contribute to this persistence, but it remains unclear when injury-associated changes represent stable, harmful cell states rather than transient stress responses, and whether their causal relevance is comparable across diseases and cell types. This review compares evidence across cell types and disease stages to address these gaps and examine implications for biomarkers, patient selection, and treatment timing. Evidence strength is disease- and cell-type specific: traumatic brain injury is most consistently associated with chronic glial abnormalities; spinal cord injury provides the clearest mechanistic links among infiltrating macrophages, neurons, and the microvasculature; and ischemic stroke has stronger support in myeloid and neurovascular compartments than in neurons or astrocytes. We use the term senescence-injury axis as a comparative framework for the possibility that persistent injury-induced senescence-related states contribute to secondary tissue dysfunction. However, reliance on single markers, tissue-level associations, and non-cell-specific interventions limits causal inference. Establishing causality requires longitudinal, cell-resolved studies with temporally controlled, cell-specific manipulation, while translation requires biomarkers that identify a persistent, potentially modifiable target state. Overall, the senescence-injury axis is a disease- and cell-type-specific framework for testing mechanisms and guiding therapeutic development, rather than an established universal causal pathway.

On the surface there does not appear to be a connection between chickenpox and migraine but, on closer examination, both conditions are associated with neuroinflammation and, because almost every human throughout history was infected with the varicella-zoster virus, it is possible that it could have triggered certain medical disorders in our ancestors. We propose a hypothesis that the acute chickenpox infection may have contributed to the appropriate environment to prime the brains of early humans for migraine. Several inflammatory mediators and immune cells involved in migraine also participate in the immune response to primary varicella infection. This, together with the fact that the virus establishes chronic latency in the trigeminal ganglia, may have contributed to a sensitized trigeminovascular system that could produce migraine if the correct susceptibility genes and exposures were present. These postinfectious neuroinflammatory reactions would also have the capability of producing a hyperexcitable cortex, hypothalamic generator and cortical spreading depression, which are the key components of migraine pathophysiology. Other supporting observations include the coexistence of varicella-zoster virus and migraine in early humans, the fact that chickenpox occurs prior to the age of migraine onset in most individuals, and the recent recognition that the proportion of US migraine patients with moderate-to-severe disability rose from 22.0% to 42.4% following implementation of the varicella vaccination program. We propose that chickenpox may have acted as an evolutionary trigger for migraine.