Background:The gut microbiota (GM) plays a critical role in colorectal cancer (CRC) immunotherapy and has attracted considerable scholarly attention in recent years. However, no bibliometric analyses on this topic have been reported to date. To elucidate the current research landscape and guide future studies, we conducted a comprehensive and multidimensional bibliometric analysis of literature from 2014 to 2024. Methods:Publications on GM and CRC immunotherapy spanning 2014-2024 were retrieved from the Web of Science (WoS) core collection and analyzed and visualized using CiteSpace, VOSviewer, and Scimago Graphica. Results:Over the past decade, the WoS core collection (WoSCC) has indexed 325 publications related to GM and CRC immunotherapy, involving 45 countries and regions, 604 institutions, and 2,206 authors. Within the top 20 most productive countries/regions, China accounts for 47% of the total output, significantly surpassing all other nations. The most prolific institution is Shanghai Jiao Tong University (N=14,471 citations; 33.64 citations per article). Among the top ten authors in terms of productivity, seven are based in China. Frontiers in Immunology has the highest publication count in this field (21 articles, accounting for 6.5%). Analysis of the most-cited literature, citation bursts, and keywords highlights a strong association between the GM and the efficacy of immunotherapy for CRC. Certain bacterial species, such as Fusobacterium nucleatum (F. nucleatum), have emerged as promising diagnostic biomarkers and therapeutic targets. Immune checkpoint inhibitors (ICIs), including nivolumab, exhibit marked efficacy in specific molecular subtypes of CRC. Additionally, microbiota-targeted interventions, such as probiotics, have been shown to enhance the therapeutic outcomes of both chemotherapy and immunotherapy. Current research is primarily focused on elucidating microbiota-immune interaction mechanisms and advancing their clinical translation. The updated 2025 literature suggests a shift from descriptive microbiome profiling toward translational applications, including microbiota modulation, engineered microbial platforms, metabolite-based mechanisms, and nanomedicine strategies. However, current evidence remains dominated by reviews and preclinical studies, with limited clinical validation. Conclusions:The relationship between GM and immunotherapy for CRC remains in the exploratory and validation stages, with a mature framework for clinical translation yet to be established. This bibliometric analysis maps the current research landscape, identifies emerging hotspots, and suggests that the field is moving toward translational application. However, unresolved causality, limited biomarker reproducibility, insufficient methodological standardization, and the lack of well-designed CRC-specific clinical trials remain major barriers to clinical implementation.
Colonoscopy is the most widely performed endoscopic procedures in the United States and considered as primary screening and surveillance modality for colorectal cancer (CRC) prevention. Effective screening and surveillance requires prompt recognition of colorectal polyps, optical diagnosis of predicted histology and safe and effective polypectomy. We aim to perform a comprehensive review of the current evidence on tools and techniques to improve polyp detection and best practices to optimize endoscopic removal. Utilization of water assisted colonoscopy, artificial intelligence (AI), image enhanced endoscopy (IEE) and distal attachment devices can improve polyp detection. Underwater endoscopic mucosal resection (EMR) has emerged as a popular technique with potentially better outcomes than conventional EMR. Modification of EMR techniques including tip-in EMR and pre-cutting EMR have also been summarized. Endoscopic full thickness resection (EFTR) is an emerging technique other than endoscopic submucosal dissection (ESD) for suitable lesions harboring early submucosal cancer. Further, we also outline the common adverse events associated with polypectomy including bleeding, perforation, post-polypectomy syndrome, and discuss preventative measures to mitigate these adverse events. Eventually, the goal of colonoscopy is to reduce interval CRC incidence and mortality, and the technology that reduces post colonoscopy CRC incidence and techniques that improve safety and recurrence would see earlier adoption in the real world practice.
Portal hypertension (PH) is a critical driver of morbidity and mortality in chronic liver disease. Although the hepatic venous pressure gradient (HVPG) remains the diagnostic gold standard, its invasiveness, high cost, and technical requirements limit its utility for routine longitudinal monitoring. Despite the proliferation of noninvasive tests (NITs), a significant research gap persists regarding their optimal integration into standardized clinical workflows and the transition from static diagnosis to dynamic, precision-based management. This review synthesizes current evidence on serum-based biomarkers [e.g., fibrosis-4 (FIB-4) index, von Willebrand factor-to-platelet ratio (VITRO) score], elastography [liver stiffness measurement (LSM), spleen stiffness measurement (SSM), and magnetic resonance elastography (MRE)], and emerging artificial intelligence (AI)-based imaging radiomics. We critically evaluate their diagnostic performance and propose a multimodal framework for the comprehensive management of PH. Evidence suggests that while traditional scores like FIB-4 are effective for initial screening, the VITRO score significantly reduces the diagnostic "grey zone" inherent in the Baveno VII criteria. SSM shows superior linear correlation with HVPG across higher pressure ranges, and MRE demonstrates the highest diagnostic reliability in obese populations. Furthermore, AI-based vascular geometry and radiomics models offer high precision for virtual HVPG estimation, though their clinical adoption remains hindered by a lack of physiological interpretability and cross-platform standardization. This review proposes a practical, multimodal management model that integrates these noninvasive tools into a cohesive clinical pathway encompassing screening, risk stratification, treatment surveillance, and prognostic assessment. We critically examine the prevailing challenges regarding cost-effectiveness, global accessibility, standardization, and disease-specific validation. This paradigm establishes a conceptual framework for virtual HVPG modeling and therapeutic simulation. It provides evidence-based guidance for implementing tiered management strategies across both primary and specialized healthcare settings, ultimately moving toward a personalized, precision-medicine approach to PH. Future research must prioritize etiology-specific validation and the development of "closed-loop" systems that link noninvasive markers directly to therapeutic response and clinical outcomes.
Background:Interleukin-6 (IL-6) and twist family bHLH transcription factor 1 (TWIST1) are critical regulators of cancer progression, including in pancreatic ductal adenocarcinoma (PDAC), but how they dynamically interact remains unclear. Therefore, this study aimed to elucidate the interaction between IL-6 and TWIST1 and explore the underlying mechanisms involved in PDAC progression. Methods:The expression levels of IL-6, IL-6R, and TWIST1 were examined in 66 PDAC patient specimens, and their correlations with clinicopathological parameters and overall survival were analyzed. Integrative bioinformatics and experimental validation identified miR-543 as a key upstream regulator of TWIST1. The IL-6/miR-543/TWIST1 feedback circuit was subsequently verified in PDAC cell lines using quantitative PCR, western blotting, and luciferase reporter assays. Chromatin immunoprecipitation and luciferase reporter assays further confirmed the binding of TWIST1 to the IL-6 promoter. In vivo xenograft models were further established to investigate both the functional relevance and therapeutic blockade of this signaling loop. Results:Elevated expression of IL-6, IL-6R, and TWIST1 was detected in PDAC tissues and was significantly associated with poor patient prognosis. Bioinformatic and experimental analyses identified miR-543 as a pivotal mediator linking IL-6 signaling to TWIST1 regulation. In vitro and in vivo experiments demonstrated that IL-6 modulated TWIST1 expression through miR-543, thereby promoting PDAC cell migration, invasion, proliferation, and clonogenic growth. TWIST1, in turn, transcriptionally upregulated IL-6 expression, forming a self-reinforcing feedback circuit. Pharmacological blockade of this loop with Tocilizumab effectively attenuated PDAC progression. Conclusions:The IL-6/miR-543/TWIST1 axis supports a dynamic feedback circuit that is associated with PDAC malignancy. Therapeutic targeting of this loop may provide an effective strategy to impede disease progression.
Background:Aflatoxin B1 (AFB1) is a potent group 1 carcinogen closely associated with hepatocellular carcinoma (HCC), particularly in regions with high dietary exposure and concurrent hepatitis B virus infection. However, the molecular mechanisms by which AFB1 promotes HCC progression remain incompletely understood, and there is a lack of prognostic models specifically tailored to AFB1-associated HCC. Integrating bioinformatics and network toxicology approaches may help identify key genes and construct reliable predictive tools for this unique subtype of liver cancer. This study aims to identify AFB1-liver cancer key genes and their functional pathways, to establish a prognosis prediction model for AFB1-liver cancer patient, and analyze its performance, and to reveal the binding characteristics between AFB1 and model proteins. Methods:Gene expression profiles and corresponding clinical data of 377 liver cancer cases were downloaded from the The Cancer Genome Atlas (TCGA) database, and 4,506 differentially expressed mRNAs were identified. AFB1 toxicity targets were predicted using SwissTargetPrediction, ChEMBL, and SEA databases, merged and deduplicated. Liver cancer-related disease targets were retrieved from GeneCard, Online Mendelian Inheritance in Man (OMIM), and Comparative Toxicogenomics Database (CTD) databases, merged and deduplicated. The intersection genes of the former three parts were calculated. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on these genes. Protein-protein interaction (PPI) network analysis was conducted to screen core genes with the highest degree values. Univariate and multivariate Cox regression analyses were further performed to identify prognosis-related genes for constructing a prognostic prediction model for AFB1-induced liver cancer. Survival analysis, risk curve analysis, and SHapley Additive exPlanations (SHAP) analysis were conducted on the model. Clinical covariates were incorporated into the model, and its performance was evaluated using the likelihood ratio test (Log-Rank), Akaike Information Criterion (AIC) value analysis, and C-index. Molecular docking analysis was performed between the core genes used to construct the model and AFB1. Results:A multivariate Cox prognostic model was developed based on 6 key genes (CCNB1, CCNB2, CHEK1, MMP1, TTK, ESR1). The model demonstrated good predictive performance in the TCGA cohort [1-year and 3-year area under the curve (AUC) >0.74] and effectively distinguished between high- and low-risk patients (P<0.001). Molecular docking results showed that AFB1 had strong binding affinity with all the above 6 prognostic gene-encoded proteins, particularly with CHEK1 protein (binding free energy =-9.4 kcal/mol). Conclusions:The Cox regression model constructed with the six genes (CCNB1, CCNB2, CHEK1, MMP1, TTK, ESR1) can effectively predict the prognosis of AFB1-induced liver cancer patients, which can reveal the potential molecular mechanisms by which AFB1 promotes the progression of liver cancer.
Background and Objective:Despite direct-acting antiviral (DAA) therapies achieving sustained virologic response (SVR) rates exceeding 95%, hepatocellular carcinoma (HCC) risk persists in cured hepatitis C virus (HCV) patients, particularly those with advanced fibrosis or concurrent metabolic dysfunction-associated steatotic liver disease (MASLD). This clinical paradox implies that HCV induces durable oncogenic molecular alterations independent of active viral replication, fundamentally challenging the notion that virologic cure equates to biological liver cure. This review aims to delineate the molecular mechanisms underlying this residual risk and to identify rational targets for chemoprevention in the post-SVR era. Methods:A narrative literature search was conducted across PubMed/MEDLINE, Scopus, and Web of Science for articles published between January 2015 and December 2025. The search strategy utilized a combination of keywords encompassing the pathogen (hepatitis C virus, HCV), clinical endpoints (sustained virologic response, SVR, hepatocellular carcinoma, HCC), and specific oncogenic mechanisms of interest, including epigenetic alterations, metabolic reprogramming, immune exhaustion, fibrosis, and lysyl oxidase-like 2 (LOXL2). Studies providing original mechanistic data in human post-SVR tissue, prospective or retrospective clinical cohort outcomes, validated animal models, or relevant meta-analyses in adult populations were included. Case reports, editorials, and non-peer-reviewed sources were excluded. Key Content and Findings:Four interconnected post-SVR oncogenic mechanisms are examined: (I) epigenetic scarring via persistent H3K27 acetylation at the SPHK1 locus sustaining oncogene expression; (II) metabolic reprogramming through the SPHK1/S1P/SREBP1c axis, driving constitutive de novo lipogenesis (DNL), reductive stress, and oxidative DNA damage; (III) immunological dysfunction characterized by TOX-driven CD8+ T-cell exhaustion and lipid-mediated natural killer (NK) cell paralysis, collectively abrogating tumor surveillance; and (IV) stromal remodeling via LOXL2-mediated collagen cross-linking perpetuating YAP/TAZ mechanotransduction. MASLD comorbidity synergistically amplifies all four mechanisms, effectively doubling HCC incidence. Conclusions:SVR represents a critical milestone, not a biological cure. These molecular scars synergize with MASLD to sustain a permissive oncogenic microenvironment long after viral eradication. Achieving true "molecular remission" will require longitudinal biorepositories for causal validation, clinically deployable multi-omics biomarker panels, and rigorously designed chemoprevention trials targeting residual epigenetic, metabolic, immune, and stromal sequelae of HCV infection.
Background and Objective:Secondary sclerosing cholangitis (SSC) comprises a heterogeneous group of identifiable etiologies causing inflammation and fibrosis of the bile ducts. Given that SSC often progresses more rapidly than primary sclerosing cholangitis and treatment is frequently etiology-directed, early recognition is critical. In this narrative review, we summarize contemporary causes of SSC and propose a diagnostic and management approach for clinicians. Methods:We performed a narrative literature review using PubMed search with medical subject headings (MeSH) and free text terms for SSC and key etiologies, including critical illness/ischemic cholangiopathy, human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), infectious, coronavirus disease 2019 (COVID-19)-associated cholangiopathy, immunoglobulin G4 (IgG4)-related/eosinophilic cholangitis, drug-induced cholangiopathy, including immune checkpoint inhibitors and ketamine, malignancy-associated, and post-procedural ischemic injury. The search included randomized trials, observation studies, case reports, case series, and practice guidelines. Two reviewers independently screened studies, reviewed full texts, and synthesized findings by etiology. Key Content and Findings:SSC following ischemic injury in critically ill patients (SSC-CIP) accounted for a significant portion of the recent literature, which presents with persistent cholestatic liver injury after intensive care unit (ICU) recovery. Infectious causes include recurrent pyogenic cholangitis, parasitic disease, HIV-related, and, most notably, given the recent pandemic, post-COVID-19 cholangiopathy. Infectious etiologies mirror SSC-CIP and may often progress to liver failure. Immune-related SSC [IgG4-related sclerosing cholangitis (IgG4-SC) and eosinophilic cholangitis] requires targeted serologies, tissue confirmation with biopsy, and typically responds briskly to corticosteroids. Drug-induced SSC is increasingly linked to immune checkpoint inhibitors, given their rise in use, as well as ketamine, and may be steroid refractory. SSC associated with malignancy requires cross-sectional imaging and tissue diagnosis. Endoscopic therapy may palliate obstruction, but liver transplantation is the definitive option for advanced disease. Conclusions:Given its diverse etiologies, SSC requires a structured evaluation that integrates exposure history, laboratory investigations, magnetic resonance cholangiopancreatography (MRCP)/endoscopic retrograde cholangiopancreatography (ERCP) patterns, and histology for diagnosis. Etiology-specific therapy may slow progression, but early transplant referral is critical for rapidly progressive phenotypes.
Background:Benign portal vein thrombosis (PVT) presents considerable technical challenges for portal vein reconstruction (PVR) during liver transplantation (LT). This study aimed to evaluate the surgical outcomes, safety profile, and clinical feasibility of ectopic physiological portal vein reconstruction (EPPVR) at non-hilar area for patients with complex benign PVT. Methods:We conducted a retrospective observational cohort study analyzing intraoperative parameters, postoperative complications, and survival outcomes in liver transplant recipients with benign PVT. Among 120 enrolled patients, 10 cases (8.3%) underwent EPPVR, including three varicose vein reconstructions (VVRs), one anterior transpancreatic bridge reconstruction, and five "pull-out" portal vein reconstructions (POPVRs) beneath the pancreas. Results:Compared with conventional orthotopic physiological portal vein reconstruction (OPPVR), EPPVR was associated with significantly longer anhepatic phase (154.50±45.43 vs. 79.77±34.56 mins, P<0.001) and greater intraoperative blood loss (1,930.00±1,515.15 vs. 766.36±707.50 mL, P=0.001). Postoperatively, the EPPVR group demonstrated markedly higher rates of elevated ascitic fluid amylase (60.0% vs. 5.5%, P<0.001) and required more frequent portal vein stent implantation in surviving patients (37.5% vs. 3.9%, P=0.008). Other complication rates and perioperative survival rate were comparable between these two groups. The above trends remained consistent in the subgroup analysis of patients with Yerdel grade 2-4 PVT, although the difference in stent implantation rates lost statistical significance (37.5% vs. 10.3%, P=0.15). Conclusions:Although EPPVR was associated with elevated perioperative risks, it did not decrease the perioperative survival rate in PVT patients. This reconstruction approach may represent a feasible alternative for complex PVT cases requiring non-standard reconstruction approaches, contingent upon thorough preoperative assessment and surgical planning.
