Early breast cancer may induce a systemic immune response before abundant tumor-derived material reaches the circulation, creating a potential source of amplified liquid-biopsy biomarkers. However, the extent to which host-response signatures can support early detection or population screening before diagnosis remains uncertain. This structured narrative review examines the biological basis, analytical platforms, evidence, clinical roles, and translational requirements of circulating autoantibodies, leukocyte transcriptomic and epigenetic profiles, immune-cell phenotypes, adaptive immune-receptor repertoires, soluble mediators, extracellular vesicles, and integrated multi-omics. PubMed/MEDLINE and citation networks were searched through August 31, 2026 using a predefined diagnostic review framework. Evidence was organized by intended use, sample timing, comparator spectrum, and validation maturity, with appraisal informed by established diagnostic-accuracy and prediction-model standards. Proof-of-concept estimates include a mean area under the curve of 0.96 for a machine-learning T-cell receptor model in 98 women, 80.8% sensitivity and 61.6% specificity for a 28-autoantibody panel, and an external-validation area under the curve of 0.951 for a 20-analyte proteome-metabolome model involving 662 participants. These estimates are not directly comparable: most derive from retrospective case-control or diagnostic cohorts with established cancer, healthy or benign comparators, post-diagnosis sampling, data-driven thresholds, and limited independent validation. Consequently, discrimination between known cases and controls must not be equated with detection of occult disease or population screening utility. Breast-specific prediagnostic evidence and screening validation remain sparse. Host-response signatures are therefore best considered investigational, complementary biological sensors rather than replacements for mammography. Their most plausible future roles include triage after equivocal imaging, enrichment for supplemental imaging, and longitudinal surveillance in high-risk populations. Translation requires prospective prediagnostic cohorts, representative benign and inflammatory controls, locked algorithms, high-specificity performance, calibration at screening prevalence, external validation, subgroup fairness, reproducibility, and evidence that testing improves cancer yield or stage distribution without unacceptable false-positive procedures, overdiagnosis, cost, or inequity.

Alpha-fetoprotein (AFP) is widely used as a serum biomarker in the evaluation of hepatocellular carcinoma and nonseminomatous germ cell tumors, but persistent AFP elevation may occasionally occur without demonstrable malignancy or active liver disease. We report a 54-year-old asymptomatic man in whom routine health screening showed persistently elevated AFP values in the 200-400 ng/mL range. Liver biochemistry was normal; viral hepatitis and human immunodeficiency virus (HIV) testing were negative; AFP-L3, protein induced by vitamin K absence or antagonist II (PIVKA-II), carcinoembryonic antigen, and carbohydrate antigen 19-9 (CA 19-9) were not elevated; and targeted imaging, including abdominal ultrasonography, triple-phase contrast-enhanced computed tomography, testicular ultrasonography, and whole-body positron emission tomography/computed tomography, revealed no evidence of malignancy. Incidental simple hepatic cysts were identified, but they lacked suspicious imaging features; cyst-fluid cytology was negative, and cyst-fluid AFP was not elevated. Over 6 years of serial follow-up, AFP remained elevated. After exclusion of hepatocellular carcinoma, germ-cell tumor, active hepatic injury, and other occult malignancy, hereditary persistence of AFP or idiopathic persistent AFP elevation was considered the most plausible explanation. This case highlights the importance of confirming persistence, excluding common malignant and hepatic causes in a stepwise manner, and avoiding repeated invasive or high-burden investigations when the patient remains clinically stable.

The success of trastuzumab deruxtecan (T-DXd) has expanded the therapeutic relevance of human epidermal growth factor receptor 2 (HER2) expression beyond the traditional HER2-positive population. This has led to evolving concepts such as HER2-low, HER2-ultralow, and HER2-null. Accurately and reproducibly distinguishing HER2 immunohistochemistry (IHC) scores 0, 0+, and 1+ remains challenging because of intratumoral heterogeneity and interobserver variability. This review discusses the challenges in HER2 assessment.

The evolution of HER2 testing and recent guideline updates were reviewed. The implications of HER2-low and HER2-ultralow breast cancers for HER2 testing were discussed.

Challenges in HER2 assessment include interobserver variability and intratumoral heterogeneity. Potential strategies for accurately and reproducibly distinguishing all HER2 IHC categories, especially HER2 IHC 0 from HER2 IHC 0+, are also discussed. Significant discordance has been reported in interpreting low-level HER2 expression. Revisiting HER2 testing guidelines, improving HER2 assessment, and developing sensitive, objective, and reproducible detection methods may reduce variability. No alternative method has been validated as a companion diagnostic for determining eligibility for T-DXd or other HER2-targeted antibody–drug conjugates. Consequently, HER2 immunohistochemistry, supplemented by reflex in situ hybridization testing for equivocal cases, remains the standard despite its limitations at the HER2-low threshold. Digital pathology, quantitative image analysis, artificial intelligence-assisted interpretation, molecular profiling, and other emerging technologies may provide more objective, sensitive, and reproducible approaches to HER2 assessment.

The evolving concepts of HER2-low, HER2-ultralow, and HER2-null emphasize the need to accurately and reproducibly distinguish HER2 IHC categories. Further research and technological advances are needed to better classify HER2 status.

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.

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.

N-acetyltransferase 10 (NAT10), a major RNA acetyltransferase mediating N4-acetylcytidine modification, has been implicated in cancer progression. We examined its cancer-type-specific associations with clinical outcomes, genomic features, and tumor immune characteristics.

We analyzed public TCGA and GTEx datasets using UCSC Xena and complementary resources, including GEPIA2, HPA, cBioPortal, TIMER2.0, STRING, LinkedOmics, and CancerSEA. Analyses included NAT10 expression, pathological stage, survival, genomic alterations, immune-cell infiltration, stemness, and molecular pathways. Exploratory immune-checkpoint-blockade (ICB) survival analyses used Kaplan–Meier Plotter cohorts receiving anti-PD-1 (n = 411), anti-PD-L1 (n = 459), or anti-CTLA-4 (n = 112).

NAT10 expression was elevated in multiple cancer types and was associated with adverse survival in selected malignancies. Higher NAT10 expression correlated positively with estimated myeloid-derived suppressor cell and cancer-associated fibroblast infiltration and negatively with several T-cell and natural killer-cell populations. NAT10-associated genes were enriched in RNA-processing pathways. In exploratory ICB cohorts, higher NAT10 expression was nominally associated with longer overall survival following anti-PD-1 therapy (hazard ratio (HR) = 0.68, 95% confidence interval (CI): 0.52–0.90) and anti-PD-L1 therapy (HR = 0.72, 95% CI: 0.56–0.92), but not anti-CTLA-4 therapy (HR = 0.66, 95% CI: 0.39–1.11).

NAT10 shows cancer-type-dependent prognostic, molecular, and immune associations. Its associations with survival after ICB are exploratory and require independent clinical and mechanistic validation.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a rapidly increasing global health concern, driven by metabolic stress, chronic inflammation, and progressive fibrotic remodeling. Myeloid-derived suppressor cells (MDSCs) have emerged as pivotal yet context-dependent modulators of MAFLD pathogenesis. This review summarizes the biological characteristics of MDSCs, their immunosuppressive mechanisms, and their multifaceted roles in MAFLD progression, including hepatic steatosis, chronic inflammation, and fibrogenesis. Quantitative synthesis reveals that murine models demonstrate MDSC expansion (∼3-fold with a high-fat diet, P < 0.05) and suppression of MDSC-associated proinflammatory mediators (e.g., MitoTEMPO reduced hepatic S100A8 mRNA by 5.9-fold, P < 0.001). In one human cohort (n = 98), hepatic CD33+/HLA-DR− MDSC density correlated with inflammation grade (Spearman r = 0.610, P < 0.001) and fibrosis stage (r = 0.687, P < 0.001), though this cross-sectional dataset lacked MAFLD-specific stratification and longitudinal validation. We further discuss emerging MDSC-targeted strategies and explicitly acknowledge current translational gaps. Collectively, this review provides a mechanistic and critically appraised framework positioning MDSCs as both promising therapeutic targets and potential biomarkers for MAFLD.

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.