Abstract Background Late‐stage neoantigen prioritisation often contains near ties among peptide–Human Leukocyte Antigen (HLA) candidates with similar presentation, processing, affinity and immunogenicity evidence. In a finite vaccine panel, unstable micro‐ordering can change which candidates cross the nomination boundary. Methods We performed an original computational study on an exact 56‐record colorectal peptide–HLA ledger with 19 source fields. Four prespecified continuous channels—presentation support, immunogenicity, transformed affinity and Transporter Associated with Antigen Processing (TAP) support—were normalised, embedded in an eight‐nearest‐neighbour Fubini–Study graph, propagated by classically evaluated continuous‐time quantum‐walk (CTQW) transport, stabilised by restart/teleport mixing and resolved by a deterministic modified black‐hole algorithm (MBHA) with non‐compensatory eligibility gates. Fixed weighted aggregation, binding‐only, immunogenicity‐only, reciprocal‐rank fusion (RRF), Borda aggregation and component controls were evaluated on the same rows. Rank stability was tested in 1000 matched seeded perturbation replicates. Results The declared presentation, immunogenicity and affinity gates retained 29 of 56 records. The full FS–CTQW–MBHA policy achieved median top‐10 retention of 0.90 (95% percentile interval 0.80–1.00) and median complete‐rank correlation of 0.999 (0.998–1.000). The fixed weighted aggregate achieved 1.00 and 0.998, respectively; binding‐only and immunogenicity‐only controls yielded 0.90/0.990 and 0.80/0.962. RRF yielded 0.80/0.927 and Borda 0.70/0.917. Thus, the full policy did not dominate every comparator on every stability metric. Conclusions The supported contribution is a stability‐first, graph‐aware decision layer that preserves very high complete‐rank reproducibility while adding non‐compensatory eligibility, redundancy governance, reason‐coded selected/reserve/failed states and deterministic replay. The study does not establish biological efficacy, clinical utility, candidate‐level Density Functional Theory/Quantum Monte Carlo (DFT/QMC) performance, biological quantum coherence or physical quantum‐computing advantage.
Abstract Background Cholangitis represents a common infectious sequela of endoscopic retrograde cholangiopancreatography (ERCP), occurring in 0.5%–3% of procedures, and may deteriorate into severe cholangitis and sepsis. Methods This narrative review synthesises contemporary evidence on the prevention and management of post‐ERCP cholangitis. The literature search followed applicable Systematic Reviews and Meta‐Analyses (PRISMA) 2020 items for narrative reviews. PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched from January 2015 to May 2026. Results The principal mechanisms involve retrograde bacterial contamination and compromised bile drainage. Preventive measures should be individualised according to preoperative cholangitis status: in patients with pre‐existing cholangitis, therapeutic antibiotics plus urgent drainage are critical; in those without, postoperative prevention is key. Prevention encompasses strict ERCP indications, early risk assessment, selective prophylactic antibiotics, meticulous intraoperative technique, and postoperative monitoring. Treatment requires prompt empirical antibiotics covering Gram‐negative bacilli and anaerobes, followed by susceptibility‐guided adjustment, together with early biliary drainage. Endoscopic drainage is preferred; percutaneous transhepatic and endoscopic ultrasound (EUS)‐guided drainage are second‐line options, and surgery is reserved as a last resort. Key recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Prophylactic antibiotic biliary lavage and novel biliary stents remain controversial. Conclusion Improved outcomes depend on early risk assessment, adequate biliary drainage, and prudent antimicrobial use. Strategies should be individualised by preoperative cholangitis status. Large‐scale, multicentre randomised controlled trials are needed to refine personalised management.
Abstract Background Gallstones affect approximately 6%–15% of adults worldwide and represent a common condition that also serves as a risk factor for hepatobiliary malignancies. Conventional ultrasound cannot provide early warning during the early metabolic phase before crystallization occurs. Methods This narrative review provides a critical synthesis of the mechanisms, clinical evidence, and translational perspectives of the bile acid–gut microbiota axis in gallstone development and hepatobiliary tumour risk. Relevant publications up to September 2026 were identified through searches of MEDLINE/PubMed, EMBASE, and Web of Science, with additional manual screening of reference lists. Randomized clinical trials, systematic reviews, meta‐analyses, key mechanistic studies, and guidelines were preferentially included. Results Patients with gallstones exhibit characteristic alterations, including elevated serum glycocholic acid (+ 0.83 µmol/L) and taurocholic acid (+ 0.51 µmol/L), reduced microbial diversity (Proteobacteria accounting for 91.59%), and a 2.5 ‐ fold increase in bai gene cluster abundance (r = 0.609). Conjugated bile acids show a dose‐response relationship with hepatocellular carcinoma risk (OR = 1.28–5.62), while late breakfast increases gallstone risk (OR = 1.435). The combination of dried blood spot sampling (R2 > 0.92) and AI‐based prediction models (AUC = 0.82–0.90) offers a feasible approach for dynamic monitoring. Conclusions This review proposes a three‐tiered stratified management strategy—DBS sampling, targeted metabolomics, and AI assessment—to provide a clinical translational reference for early warning and precision prevention of gallstones and hepatobiliary tumours.
Abstract Background CRISPR‐derived epigenome editors enable locus‐specific control of gene expression without changing the underlying DNA sequence, creating therapeutic opportunities for dosage‐sensitive disorders, imprinting diseases, aberrant gene activation and reversible cell‐state engineering. Main body This scoping review maps mechanistic classes, target‐validation strategies, emerging platforms, translational evidence and unresolved risks of CRISPR‐based epigenome editing. A structured PubMed/MEDLINE search and citation‐chain review were updated in July 2026, with a targeted update of recent peer‐reviewed literature before revision. The field has progressed from CRISPR interference (CRISPRi) and activation to direct rewriting of DNA methylation and histone marks, programmable transcriptional memory, compact effectors, transient ribonucleoprotein or mRNA delivery, and externally controllable systems. Preclinical studies demonstrate correction of dosage‐sensitive and imprinting phenotypes, programmable regulation in human neurons and primary immune cells, and durable in vivo silencing after transient delivery. Target selection nevertheless requires orthogonal validation: nuclease knockout, conditional loss‐of‐function, CRISPRi, rescue, and reverse‐editing experiments answer different biological questions and should be interpreted together when establishing causality. The absence of DNA cleavage does not make epigenome editing intrinsically risk free. Development must address seed‐sequence‐mediated off‐target regulation, chromatin spreading, allele and cell‐type specificity, persistence, immune responses, delivery constraints and uncertainty regarding the relationship between a molecular epigenetic change and clinical phenotype. CONCLUSION CRISPR epigenome editing is approaching clinical translation, but adoption will depend on rigorous causal target validation, standardized reporting, multilayer specificity assays, controllable delivery and evidence that corrected expression remains within a safe physiological window.
Abstract Aims Gamma‐aminobutyric acid (GABA)ergic dysfunction is central to Tourette syndrome (TS), yet evidence linking peripheral signals, upstream regulation, pharmacologic response and striatal cellular context remains fragmented. We investigated whether a GABA‐defined peripheral molecular state in TS could be linked to candidate regulatory signals, pharmacologic response, striatal cell‐type localisation, and local communication networks. Methods We integrated peripheral blood mRNA (GSE30470), serum miRNA profiles (GSE146509), chronic diazepam brain transcriptomes (GSE76700) and striatal single‐cell RNA‐seq (GSE116470). TS samples were stratified by a GABA_index derived from GABA‐related gene expression. Analyses included differential expression, miRNA target enrichment, disease‐drug reversal, cell‐type localisation, and ligand‐receptor communication. Results GABA_index stratification separated TS into GABA_Low and GABA_High states, revealing 1290 differentially expressed genes. The only high‐confidence serum miRNA was hsa‐miR‐483‐3p; enrichment of its validated targets in neurotrophin, Ras, Rap1, axon guidance and cAMP pathways indicates upstream cortico‐striato‐thalamo‐cortical (CSTC) regulation. Chronic diazepam reversed the TS transcriptional signature in cortex, negatively enriching TS_Up and positively enriching TS_Down genes. Single‐cell analysis localised GABA/CSTC programs to medium spiny neurons and interneurons; communication analysis revealed an extracellular matrix/adhesion‐centred striatal microenvironment with fibroblast and vascular leptomeningeal cell contributions. Conclusion TS is associated with a peripheral GABA‐centric molecular state linked to upstream miRNA regulation and striatal neuronal microenvironments.
