The prognostic relevance of baseline low-level viremia (LLV) after hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) diagnosis remains uncertain. We evaluated the association between baseline LLV and overall survival (OS), explored related biological features, and developed survival prediction models for patients with baseline LLV.

This retrospective study included 921 patients with HBV-HCC: 611 with baseline LLV and 310 with HBV DNA <20 IU/mL. Propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and Cox regression were used to assess the association between baseline HBV DNA status and OS. Peripheral T cell subsets and selected markers of hepatic functional reserve, hepatocellular injury, and systemic inflammation were explored. Patients with baseline LLV were randomly divided into training and reserved internal validation sets. Model 1 used the full candidate variable set, whereas Model 2 used non-imaging variables. Predictors were selected using LASSO Cox regression and Boruta, and five survival algorithms were compared within the training set.

Baseline LLV was associated with poorer OS. After PSM, HBV DNA <20 IU/mL was associated with lower adjusted mortality than LLV (hazard ratio, 0.688; 95% confidence interval, 0.543-0.872; P = 0.002), with similar findings after IPTW. Patients with LLV had a lower peripheral CD4/CD8 ratio, and exploratory analyses identified significant indirect associations through albumin, aspartate aminotransferase, and systemic immune-inflammation response index. Model 1 retained tumor size, tumor multiplicity, portal vein tumor thrombus, cholinesterase, alkaline phosphatase, and alpha-fetoprotein; Model 2 retained gamma-glutamyl transferase, cholinesterase, alkaline phosphatase, and alpha-fetoprotein. Random survival forest was selected based on overall training performance. In the reserved validation set, the 1-, 3-, and 5-year time-dependent AUCs were 0.824, 0.777, and 0.765 for Model 1 and 0.769, 0.742, and 0.723 for Model 2, respectively. Both models showed good calibration and positive net benefit.

Baseline LLV remained prognostically relevant after HCC diagnosis and was accompanied by exploratory differences in systemic inflammation and the relative balance of peripheral T cell subsets. These findings support closer virological monitoring and individualized risk assessment.

Myasthenia gravis (MG) is a heterogeneous neuroimmune disorder in which pathogenic autoantibodies impair neuromuscular junction transmission and produce fluctuating skeletal muscle weakness. Although conventional therapy with acetylcholinesterase inhibitors, corticosteroids, and broad immunosuppressants remains effective for many patients, its limitations are increasingly evident, including delayed onset, cumulative toxicity, and inadequate control in refractory disease. These challenges have accelerated the transition from non-selective immunosuppression to biologic and other targeted therapies. Recent advances in MG have revealed that treatment response is strongly shaped by disease heterogeneity across molecular, cellular, and structural levels. Antibody-defined subtypes, including acetylcholine receptor (AChR)-positive, muscle-specific tyrosine kinase (MuSK)-positive, low-density lipoprotein receptor-related protein 4 (LRP4)-positive, and seronegative MG, differ in immune mechanism, complement dependence, and therapeutic vulnerability. On this basis, neonatal Fc receptor (FcRn) antagonists, complement inhibitors, and B-cell-directed therapies have emerged as major biologic classes that increasingly enable mechanism-informed treatment selection. At the same time, resistance remains an important clinical problem, arising from persistent autoreactive immune compartments, pathway-level escape, and irreversible neuromuscular junction damage that may sustain disability despite immunological control. In this review, we discuss how immunological heterogeneity provides the biological rationale for targeted therapy in MG and synthesize current evidence for established and emerging biologics, including FcRn antagonists, complement inhibitors, B-cell- and plasma-cell-directed strategies, and cell-based immunotherapies. We further examine the major barriers that now define the field, particularly long-term safety, infection risk, treatment resistance, incomplete biomarker frameworks, and the distinction between active immune refractoriness and fixed structural impairment. Finally, we outline how biomarker-guided stratification, dynamic monitoring, and integration of neuroprotective or regenerative approaches may help move MG management from empiric escalation toward safer and more precise individualized care.

Postoperative delirium is common after major head and neck cancer surgery. We investigated whether intraoperative dexmedetomidine infusion was associated with a lower incidence of postoperative delirium in patients undergoing head and neck cancer surgery requiring free-flap reconstruction.

This was a delirium-focused secondary analysis of a single-centre, randomized, double-blind, placebo-controlled trial. Adult patients with head and neck cancer scheduled for elective surgery requiring free-flap reconstruction under general anaesthesia were randomly assigned to receive intraoperative dexmedetomidine infusion at 0.3 μg kg^-1h^-1 until 1 h before the end of surgery; subjects in the placebo group were given comparable volumes of normal saline. The primary outcome was the incidence of delirium during the first 5 postoperative days, assessed once daily using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or the 3-Minute Diagnostic Confusion Assessment Method (3D-CAM).

There was less delirium during the initial 5 postoperative days in patients assigned to dexmedetomidine (14.9%, 7 of 47 patients) than in those given placebo (34.7%, 17 of 49 patients). Dexmedetomidine was associated with lower odds of postoperative delirium after adjustment for age, preoperative Mini-Mental State Examination score, and operative time (adjusted odds ratio 0.31, 95% confidence interval 0.10-0.92; p = 0.036). Postoperative pain and early sleep outcomes were improved by dexmedetomidine. Haemodynamic adverse events and postoperative complications did not differ significantly between groups.

In patients undergoing head and neck cancer surgery with free-flap reconstruction, intraoperative dexmedetomidine infusion was associated with a lower incidence of postoperative delirium during the first 5 postoperative days, without an apparent increase in perioperative adverse events.

ChiCTR2300067376.

Periodontal disease and lung cancer are major global health burdens, and epidemiological evidence suggests a potential association between them. However, whether this relationship is independent of smoking-a strong common risk factor-remains controversial. This review systematically summarizes current evidence on the association, with emphasis on smoking confounding and underlying biological mechanisms. Meta-analyses consistently show a significant positive association, with adjusted hazard ratios ranging from 1.24 to 1.71 and dose-response relationships across disease severity and tooth loss. After rigorous statistical adjustment for smoking, most large cohort studies still show a robust association, though findings in never-smokers are inconsistent, suggesting possible residual confounding. Mechanistically, the "oral-lung axis" links periodontitis to lung carcinogenesis via three pathways: microbial translocation of pathogens such as Fusobacterium nucleatum, chronic inflammation-driven immune dysregulation involving Treg and IL-6, and epigenetic modifications including shared DNA methylation sites. Smoking may also act synergistically with periodontitis to amplify carcinogenic risk. Future research should prioritize precisely quantified smoking exposure, formal interaction analyses, and longitudinal multi-omics studies to support causal inference. This review provides a theoretical foundation for incorporating oral health assessment into lung cancer prevention strategies.

Hepatocellular carcinoma remains difficult to treat because immune resistance is organized not only by malignant cell states but also by the spatial architecture of the tumor microenvironment. Single-cell RNA sequencing has clarified cellular heterogeneity in liver cancer, yet tissue dissociation removes the positional relationships that determine whether immune cells can reach and eliminate tumor nests. Spatial transcriptomic, proteomic, and multiplex imaging technologies now make it possible to map immune exclusion, stromal barriers, vascular gatekeeping, tertiary lymphoid structures, macrophage and fibroblast programs, and metabolic checkpoints within intact tumor tissue. This review integrates recent single-cell and spatial multi-omics evidence to explain how suppressive neighborhoods emerge in hepatocellular carcinoma and how they shape immunotherapy response. We discuss the mechanisms through which malignant, myeloid, lymphoid, endothelial, and stromal populations interact across spatial niches, and we examine how these maps can inform biomarker discovery, patient stratification, and rational combination therapy. We also highlight limitations in cohort design, sampling depth, analytical integration, and clinical validation that currently constrain translation. By linking cellular states to their tissue coordinates, spatial omics provides a framework for understanding why ICI succeed in some tumors but fail in others. Integrating single-cell resolution with spatial context may help convert descriptive tumor atlases into clinically actionable maps for precision immuno-oncology.

Lower anogenital tract malignancies comprise anatomically adjacent but biologically heterogeneous epithelial cancers of the cervix, vulva, vagina, anal canal and penis. This narrative and conceptual Review used a transparent literature search to examine how human papillomavirus (HPV) etiology intersects with tumor lineage, somatic alterations, antigen-presentation competence, immune-cell state and spatial organization. Evidence quality is heterogeneous: cervical cancer is supported by the largest genomic, single-cell, spatial and randomized-trial literature, whereas vaginal, vulvar and penile cancers remain constrained by small retrospective cohorts and cross-site extrapolation. HPV-associated tumors retain non-self E6/E7 antigens, but viral transcription does not ensure peptide presentation, dendritic-cell priming or epithelial access by functional T cells. HPV-independent tumors lack constitutive viral antigens yet may generate mutation- or differentiation-derived immunity and checkpoint-restrained myeloid-lymphoid niches. We therefore distinguish etiological status from functional immune phenotype and critically appraise three spatial architectures-an inflamed/epithelial-penetrating pattern, a stromally excluded pattern, and an immune-desert pattern-together with an immunosuppressive functional overlay that may occur in any architecture. Clinical evidence is graded separately from mechanistic inference: immune checkpoint blockade has established roles in defined cervical and anal cancer settings, whereas therapeutic vaccines, tumor-infiltrating lymphocytes, T-cell receptor-engineered therapies, myeloid or stromal sensitization and artificial-intelligence-guided selection remain investigational or context dependent. A three-tier biomarker framework is proposed, separating routine clinical assays from extended translational profiling and exploratory single-cell, spatial and artificial-intelligence methods. This framework is hypothesis-generating, not a validated treatment-selection algorithm; assay combinations, thresholds and incremental clinical utility require prospective, multicenter and site-stratified validation.

Radiotherapy is indispensable for cancer control, yet acute and late normal-tissue toxicities remain major limits to treatment intensity and survivorship. Considerable interindividual variation persists after clinical and dosimetric factors are considered, motivating radiogenomic studies of inherited susceptibility. This review compares common and rare germline variation, association and sequencing designs, polygenic risk scores, and functional evidence through an immunological framework. Radiation-induced DNA damage and organelle stress release danger-associated signals and cytosolic DNA that engage pattern-recognition pathways, including cGAS-STING, and initiate endothelial and epithelial inflammatory programs. Cytokines, chemokines, inflammasomes, recruited myeloid cells, lymphocytes, senescent cells, and fibroblasts then determine whether injury resolves or progresses to chronic immune dysregulation and fibrosis. Germline variants may modify these responses, but pathway plausibility is not equivalent to variant-specific causality. The strongest evidence combines a replicated clinical association with dose adjustment, regulatory annotation, allele-specific perturbation, and validation in organ-relevant immune-stromal models. Integrated prediction should combine genomic susceptibility with normal-tissue imaging, dose-volume exposure, baseline inflammatory state, comorbidity, and systemic therapy. Germline associations with checkpoint-inhibitor toxicity provide a rationale for studying radio-immunotherapy, although radiation-specific genetic interactions remain unvalidated. No current common variant or polygenic score justifies reducing curative dose or target coverage. Near-term translation is more appropriately directed toward risk-adapted surveillance, supportive care, and genotype-enriched prevention trials. An immune-centered radiogenomic framework can connect inherited susceptibility to damage sensing, inflammatory amplification, resolution failure, and tissue remodeling while preserving the distinction between mechanistic evidence and clinical utility. Graphical summary: inherited susceptibility modifies the sequence from radiation-induced damage sensing and immune activation to resolution, repair, or chronic inflammation and fibrosis.

Polyendocrine metabolic ovarian syndrome (PMOS) is the new consensus name for polycystic ovary syndrome (PCOS), emphasizing the broader multisystem nature of the condition. Altered autonomic nervous system (ANS) regulation may provide an integrative physiological perspective on the reproductive, metabolic, and cardiovascular alterations associated with PMOS/PCOS. Heart rate variability (HRV) provides a non-invasive approach for assessing autonomic regulation; however, conventional HRV indices primarily characterize the magnitude and spectral distribution of variability. We therefore propose a multidimensional framework for investigating autonomic alterations in PMOS/PCOS. It integrates conventional HRV with heart rate fragmentation, nonlinear complexity, and deceleration and acceleration capacities derived from phase-rectified signal averaging. This Review evaluates the evidence supporting these dimensions and discusses how validated wearable monitoring, standardized preprocessing, and digital phenotyping may support future context-aware autonomic research. Prospective PMOS/PCOS-specific validation is required before these approaches can inform metabolic risk stratification, treatment monitoring, or clinical decision-making.

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma and remains highly heterogeneous in prognosis. Palmitoylation, an important post-translational modification, has been implicated in tumor biology, but its role in DLBCL, particularly in relation to the immune microenvironment, remains unclear.

Transcriptomic and clinical data from 706 patients with DLBCL were obtained from the Gene Expression Omnibus database. Prognosis-associated palmitoylation-related genes were identified by differential expression and univariate Cox regression analyses. An optimal prognostic model was developed by comparing 101 machine learning algorithm combinations and was further integrated with clinical variables to construct a nomogram. The tumor immune microenvironment was evaluated using immune infiltration, immune function, immune checkpoint, and Tumor Immune Dysfunction and Exclusion analyses. Weighted gene co-expression network analysis (WGCNA) and Mendelian randomization (MR) were performed to identify key genes, followed by experimental validation.

A 33-gene palmitoylation-related signature (PRS) was established and evaluated across multiple cohorts. PRS was an independent prognostic factor of DLBCL and showed consistent prognostic performance across datasets. Low-risk patients showed higher immune cell infiltration and more active immune function, whereas high-risk patients showed a greater predicted potential to respond to immune checkpoint inhibitor therapy. A nomogram integrating PRS with clinical characteristics also showed favorable predictive accuracy. In addition, two palmitoylation-related molecular subtypes with distinct transcriptomic features, survival outcomes, and immune microenvironment characteristics were identified in DLBCL. CEACAM3 was prioritized as a key candidate gene based on integrated WGCNA and MR analyses, and functional experiments showed that CEACAM3 knockdown suppressed proliferation and invasion and promoted apoptosis, whereas CEACAM3 overexpression enhanced proliferation and invasion, reduced apoptosis, and promoted tumor growth.

The PRS captures prognostic heterogeneity and distinct immune microenvironment features in DLBCL. PRS may provide a useful tool for risk stratification, and CEACAM3 may serve as a potential biomarker and therapeutic target in DLBCL.

Transcatheter arterial chemoembolization (TACE) with lenvatinib and programmed death-1 (PD-1) inhibitors therapy (triple therapy) demonstrated encouraging efficacy for unresectable hepatocellular carcinoma (uHCC). This study developed and validated a novel prognostic model to evaluate prognosis of uHCC patients with triple therapy, and identify patients who may benefit from triple therapy.

uHCC patients receiving triple therapy were retrospectively enrolled from multiple centers. Overall survival (OS) was the primary endpoint. The prognostic model was developed based on multivariate Cox regression derived predictors of OS. Prognosis was evaluated by Kaplan-Meier survival curves.

265 uHCC patients were enrolled (training cohort: n = 160; validation cohort: n = 105). The objective response and disease control rate were 52.5 and 77.7%, respectively. The optimal cut-off point for fibrin degradation products (FDP) and serum iron level were determined as 4.7 μg/dL and 60.0 μg/dL, respectively. Multivariate Cox regression identified FDP, serum iron level and tumor burden score (TBS) as independent predictors of OS, and these clinical parameters established the FIT model. The FIT model demonstrated favorable discriminative capability for predicting OS with AUC of 0.809 (95% CI: 0.740-0.879) and 0.798 (95% CI: 0.710-0.886) in the training and validation cohorts, respectively. Kaplan-Meier analyses revealed significant prognostic stratification for OS and progression-free survival (PFS) among risk groups defined by FIT model (p < 0.001). Subgroup analyses in alpha-fetoprotein (AFP), tumor number and Barcelona Clinic Liver Cancer (BCLC) stage subsets confirmed the prognostic relevance of FIT model in uHCC.

The novel clinical FIT model could effectively predict survival of uHCC patients receiving triple therapy, and facilitate prognostic stratification.