Background:Hepatocellular carcinoma (HCC) exhibits profound molecular heterogeneity and aberrant cellular senescence. This study systematically dissects the senescence-associated molecular landscape to identify key regulators driving HCC progression and immune evasion. Methods:Integrating multi-cohort transcriptomic datasets, we developed a robust prognostic signature using 101 machine-learning models, identifying prognostic signature. We employed preliminary proteomic, exploratory metabolomic, and single-cell RNA sequencing (scRNA-seq) analyses to explore multi-omics alterations. The functional senescence status and MCM7 were validated in a clinical HCC cohort by RT-qPCR, Western blotting, immunohistochemistry, and multiplex immunofluorescence (mIF). Causality was established using in vitro functional assays in HepG2 cells. Results:A 12-gene random survival forest (RSF) signature accurately predicted patient survival across independent cohorts. MCM7 emerged as a central senescence-associated driver. ScRNA-seq and mIF confirmed MCM7 characterizes a highly proliferative, clonally expanding subset of CD8+ T cells within the tumor microenvironment. In vitro, MCM7 knockdown significantly inhibited HepG2 cell proliferation and upregulated senescence enforcers p16 and p21, whereas overexpression facilitated evasion. Additionally, TIDE analysis revealed that high-risk patients exhibited elevated immune evasion potential, predicting poor immunotherapy response. Conclusion:This integrative multi-omics framework uncovers an MCM7 MCM7-driven senescence-associated axis promising HCC progression and immune dysfunction, offering a robust tool for prognostic stratification and novel therapeutic insights.

Background: The incidence of early-onset pancreatic cancer (EOPC, age <=50 years) is rising, yet whether it represents a distinct entity from average-onset pancreatic cancer (AOPC) remains unclear. We compared clinicopathological characteristics, treatment, and survival between EOPC and AOPC. Methods: We searched PubMed, Embase, Web of Science, Cochrane Library, and Scopus from inception to Jan 20, 2026, for observational studies comparing EOPC with AOPC. Two reviewers independently screened, extracted data, and assessed quality (Newcastle-Ottawa Scale and ROBINS-E). Hazard ratios (HR) and odds ratios (OR) were pooled using random-effects models with REML and Hartung-Knapp-Sidik-Jonkman correction. Evidence certainty was assessed using GRADE. This study is registered with PROSPERO, CRD420261346604. Findings: 49 studies (1,659,520 patients) from 15 countries were included and 39 meta-analyses performed. EOPC patients presented with more advanced disease (stage IV, OR 1·18; metastatic, OR 1·15) yet received substantially more treatment–chemotherapy utilisation was more than double that of AOPC (OR 2·04, 1·69–2·45; p<0·001; no treatment, OR 0·42)–resulting in comparable overall survival (HR 1·03, 95% CI 0·87–1·22; p=0·74; prediction interval 0·51–2·08; 19 studies; very low certainty). EOPC patients were more likely to be male (OR 1·23) and to smoke (OR 1·27), with markedly lower diabetes prevalence (OR 0·40). Meta-regression identified a significant non-linear (U-shaped) relationship between age threshold and survival (p=0·007). All 39 outcomes were rated very low certainty. Interpretation: Despite more advanced disease, EOPC patients receive substantially more aggressive treatment and achieve comparable survival. The lower diabetes prevalence and distinct tumour location suggest different aetiological pathways. These findings support aggressive treatment regardless of age and highlight the need for molecular characterisation of early-onset disease, including universal genomic profiling and equitable access to precision therapies.

Objective This study aimed to analyze the risk factors associated with early allograft dysfunction (EAD) following orthotopic liver transplantation (OLT) and ex vivo liver resection combined with autologous liver transplantation (ELRA), and to develop predictive models with the ultimate goal of optimizing clinical pathways and improving patient outcomes. Methods This retrospective study analyzed patients who underwent LT in the ICU of between January 2013 and April 2024. Patients were categorized based on EAD occurrence and surgical procedure. Comparative analyses were conducted across the groups to identify the independent risk factors for EAD, which were subsequently used to develop a predictive model. Results In OLT recipients, postoperative day 0 (POD0) procalcitonin, POD0 interleukin-6 (IL-6), and POD0 prothrombin time were identified as the primary risk factors for EAD. In ELRA recipients, intraoperative packed red blood cell transfusion volume, POD0 international normalized ratio (INR), and postoperative epinephrine use were significantly associated with EAD development. Based on these findings, separate nomograms were constructed for each surgical cohort. Both nomogram models demonstrated satisfactory goodness-of-fit, and the decision curve analysis (DCA) together with the clinical impact curve (CIC) confirmed their clinical utility, thereby enhancing the early identification of EAD. Conclusions This study suggests that the pathogenic mechanisms underlying EAD differ according to the type of liver transplantation performed. In OLT, EAD appears to be predominantly driven by inflammatory-immune cascades, whereas in ELRA, it is primarily governed by perioperative hemodynamic and circulatory instability. The category-specific predictive models developed in this study demonstrated superior accuracy in identifying high-risk patients along distinct pathological pathways. Accordingly, differentiated clinical management strategies are warranted: OLT recipients may benefit from early and targeted anti-inflammatory intervention, while ELRA patients require meticulous monitoring and optimization of volume status and hemodynamic parameters.

Background:Intestinal autotransplantation (IATx) facilitates radical resection for advanced intra-abdominal cancers involving major vessels, which were previously deemed unresectable. This study systematically reviewed and meta-analyzed its perioperative safety and mid-term survival outcomes. Methods:A search of databases was conducted up to December 2025, adhering to PRISMA guidelines. Studies reporting outcomes of IATx were included in the review. A total of 12 studies involving 160 patients were reviewed, with meta-analysis performed on six studies comprising 122 patients, using random-effects models. Primary outcomes included the 3-year overall survival (OS) rate, 90-day mortality, major complications (Clavien-Dindo ≥ III), and R0 resection rates. Secondary outcomes involved cold ischemia time, operative time, and length of hospital stay. Study quality was assessed by using the MINORS criteria. Results:The pooled 3-year OS rate was 57.9% (95% CI, 34.1%-75.7%; 4 studies; I 2 = 36.8%, P = 0.040). Analysis of perioperative outcomes from six studies (122 patients) revealed a pooled 90-day mortality of 6.6% (95% CI, 3.1%-13.5%; I 2 = 0%), a major complication rate (Clavien-Dindo ≥ III) of 27.9% (95% CI, 12.9%-50.3%; I 2 = 71.8%), and an R0 resection rate of 92.3% (95% CI, 84.3%-96.4%; I 2 = 0%). The pooled mean cold ischemia time was 124 minutes (95% CI, 75-173 minutes; 5 studies; I 2 = 98.9%), the operative time was 10.4 h (95% CI, 9.1-11.7 h; 6 studies; I 2 = 90.4%), and the postoperative length of stay averaged 22 days (95% CI, 19-25 days; 5 studies; I 2 = 35%). Conclusions:IATx for unresectable complex intra-abdominal tumors demonstrates high R0 resection rates, low mortality, and encouraging 3-year OS outcomes. Given the procedural complexity, IATx should be performed exclusively at expert centers. Further long-term follow-up studies are necessary to validate these findings.

Hepatic ischemia-reperfusion injury (HIRI) is a major challenge in liver surgery, and effective pharmacological interventions are lacking. Salvianolic acid C (SaC) has shown protective effects in various pathologies, but its role in HIRI remains unclear. This study investigated whether SaC protects against HIRI and elucidated the underlying mechanisms. Bioinformatics analysis of GSE151648 identified differentially expressed heat shock proteins (HSPs) and associated pathways. Molecular docking predicted SaC binding to HSP90α and AKT. A murine HIRI model was established with SaC (10 mg/kg, i.p.) pretreatment for 7 days. Histology, serum transaminases, and oxidative stress markers assessed liver injury. HSP90α inhibition used 17-AAG; in vitro hypoxia/reoxygenation (H/R) experiments used AML12 hepatocytes. Clinical validation used paired liver tissues from patients undergoing ex vivo liver resection and autotransplantation. Twenty-one HSP genes were differentially expressed, with HSP90α as a core hub gene in the PI3K/AKT pathway. SaC showed high binding affinity for HSP90α (-8.7 kcal/mol) and p-AKT1 (-10.9 kcal/mol). In mice, SaC upregulated HSP90α, reduced necrosis and serum transaminases, decreased MDA and increased GSH and SOD, suppressed TNF-α, IL-1β, and IL-6, and reduced apoptosis (Bax/Bcl-2, cleaved caspase-3), while activating PI3K/AKT. These effects were abolished by 17-AAG and confirmed in H/R-treated AML12 cells. HSP90α was also upregulated in post-transplant human livers. SaC protects against HIRI by upregulating HSP90α and activating PI3K/AKT, thereby alleviating oxidative stress, inflammation, apoptosis, and necrosis. These findings support SaC as a potential therapeutic strategy for HIRI.

Background Heat shock proteins (HSPs) are key regulators in the pathogenesis, diagnosis, and treatment of Hepatocellular Carcinoma (HCC), but a comprehensive bibliometric analysis covering the latest research progress is lacking. This study aims to systematically depict the research landscape, collaboration network, and emerging trends of HSPs in HCC from 2015 to September 2025. Methods Based on 817 publications retrieved from the Web of Science Core Collection (WoSCC), a bibliometric analysis was conducted using CiteSpace, VOSviewer, and Bibliometrix R tools. Results The annual publication output in this field showed fluctuating growth, with the cumulative scale continuously expanding and academic attention steadily increasing. China was the largest contributor with 503 papers (accounting for 59.32%), whereas the United States played a central role in international collaboration and demonstrated high academic influence (average 33.69 citations per paper, total link strength 74). Institutional analysis revealed that Chinese institutions, including Zhejiang University and Fudan University, formed close domestic collaboration networks, with Fudan University ranking first in influence (average 33.30 citations per paper). Keyword analysis indicated that research themes are evolving from classical mechanisms such as "apoptosis" and "oxidative stress" toward emerging directions, including "network pharmacology" (with the highest burst strength), "tumor microenvironment (TME)", and "nanoparticles". Highly cited publications were predominantly reviews (70%), focusing on mechanisms such as ferroptosis, suggesting the field is experiencing a phase of knowledge synthesis alongside active original investigation. Conclusion This study comprehensively reveals the development characteristics of the field, providing crucial insights for scholars to understand research trends, plan frontier directions, and promote translational research.

Background:The global burden of gastrointestinal tract cancers (GICs)-specifically liver cancer (LC), colorectal cancer (CRC), gallbladder and biliary tract cancers (GBTCs), and pancreatic cancer (PC)-attributable to high body mass index (BMI) is of increasing concern, especially among middle-aged and elderly populations. Methods:Using data from the Global Burden of Disease (GBD) Study 1990-2021, we assessed deaths, disability-adjusted life years (DALYs), age-standardized mortality rates (ASMR), and estimated annual percentage changes (EAPC) for LC, GBTCs, CRC, and PC attributable to high BMI in middle-aged and elderly populations. We analyzed regional, national, and Socio-demographic Index (SDI)-stratified patterns and their association with SDI and Human Development Index (HDI). Forecasts to 2050 were based on historical trends in these age groups. Results:From 1990 to 2021, LC deaths increased by 363% to 40,958, with ASMR rising from 1.0 to 2.2 per 100,000 (EAPC: 2.4%). GBTC deaths rose by 109% to 19,035, but ASMR slightly declined from 1.1 to 1.0 (EAPC: -0.5%). CRC deaths increased by 140% to 92,013, with stable ASMR (4.9 to 5.0; EAPC: -0.1%). Pancreatic cancer mortality also increased globally (EAPC: 4.4%), with high-SDI regions bearing the highest burden and middle-SDI regions experiencing the fastest growth (EAPC: 18.1%). East Asia bore the highest burden for all cancers, while South Asia showed the fastest mortality increases (EAPC: 5.4% for LC, 2.9% for CRC). At the national level, China and India contributed the largest share of deaths, while Indonesia and Vietnam showed the fastest growth in mortality. High-SDI regions had the largest absolute burden, but middle-SDI regions exhibited the fastest growth. All cancers showed male predominance, peaking at ages 60-79 years (LC: 60-64; GBTCs: 65-69; CRC: 75-79). ASMR followed an inverted U-shaped curve with SDI and HDI, peaking at SDI 0.7-0.9. By 2050, CRC and LC are projected to see rising DALYs and Years Lived with Disability (YLDs) in middle-aged and elderly populations, while GBTCs remain stable, with declining Years of Life Lost (YLLs) rates across all cancers. Conclusion:The escalating burden of high BMI-related GICs-particularly LC, CRC, GBTCs, and PC-in aging populations, especially in developing regions, highlights the urgent need for targeted interventions in prevention, early detection, and survivorship care.

The advent of conversion therapy for hepatocellular carcinoma (HCC) marks a critical transition from palliative care to curative-intent surgery. While clinical success rates are rising, the molecular determinants of sustained remission remain inadequately defined. We propose that effective downstaging may indicate a comprehensive modulation of the tumor immune microenvironment potentially transitioning it from an immune-excluded to an inflamed phenotype based on early translational correlative data. However, the aggressive therapeutic selective pressure of targeted, immune, and locoregional therapies paradoxically fuels clonal evolution. In specific contexts, this therapeutic stress is hypothesized to drive treatment-resistant subclones through mechanisms such as Wnt/β-catenin signaling and metabolic adaptation. To navigate this therapeutic barrier, we advocate shifting the clinical objective from anatomical to biological resectability, operationally defined by a provisional set of measurable criteria including ctDNA clearance, robust CD8+ T-cell infiltration, and tertiary lymphoid structure maturation. By implementing a multidimensional surveillance framework that leverages liquid biopsies and AI-radiomics to track subclonal dynamics and minimal residual disease, clinicians can guide precise surgical interventions and intercept resistance, making a curative horizon attainable.

Background:The prognosis for patients with small hepatocellular carcinoma (HCC) after curative resection is variable. Early recurrence (within 2 years) remains a significant clinical challenge, closely associated with poor long-term outcomes. Although inflammatory biomarkers have shown prognostic value, integrated models for predicting both early recurrence and long-term survival are lacking. This study developed and validated prognostic models for overall survival (OS) and recurrence-free survival (RFS) in HCC patients post-resection, employing propensity score matching (PSM) to control for confounders between small (≤3 cm) and non-small HCC, with an emphasis on assessing model performance within the small HCC subgroup. Methods:A retrospective analysis of HCC patients who underwent hepatectomy was performed. PSM (1:1 nearest-neighbor with replacement) was applied to balance baseline characteristics between small and non-small HCC groups. After matching, a balanced cohort was used for survival analysis. Independent prognostic factors were identified through Cox regression. A traditional nomogram and risk score models were developed and compared against three machine learning models (LASSO-Cox, Random Forest, XGBoost) using time-dependent AUC. Results:Following PSM, 165 patients (90 with small HCC and 75 with non-small HCC) were included. Small HCC patients demonstrated significantly better OS and RFS (both p < 0.01). Multivariate analysis identified tumor size, SII, and AAR as independent predictors for OS, and tumor size, PAR, NLR, and GPR for RFS. The LASSO-Cox model exhibited the best overall performance, achieving the highest accuracy for early recurrence (2-year RFS AUC = 0.727) and competitive accuracy for long-term survival (5-year OS AUC = 0.698). The nomogram retained good interpretability (5-year OS AUC = 0.691). Conclusion:This study establishes a comprehensive prognostic framework for small HCC, integrating tumor size with systemic inflammation (SII, NLR), liver function (AAR, GPR), and nutritional-coagulation status (PAR). The LASSO-Cox model is recommended for predicting both early recurrence and long-term survival, offering refined risk stratification to guide postoperative management.

Echinococcus multilocularis larval tapeworm infection in humans is considered a serious public health issue. The immune interaction between parasites and their hosts is extremely important. NK cells are known innate immune cells that play important roles during infection and tumour progression. However, the possible role of NK cells in hepatic alveolar echinococcosis is not completely clear. In this study, we investigated the functional decrease in NK cells in hepatic alveolar echinococcosis (AE) patients.MethodsUsing human liver tissue samples from 10 patients with hepatic AE, flow cytometry was used to detect the expression of NKG2A molecules on the surface of NK cells, and the correlations between NKG2A+ expression and lesion size, alkaline phosphatase (ALP) levels in close lesion tissues (CLTs) and distal lesion tissues (DLTs) in the liver, and the secretion of functional molecules by NKG2A+ NK cells were analysed.ResultsThe expression of NKG2A on CD56dim and CD56bright NK cells in DLTs and CLTs revealed that the percentage of NKG2A+CD56dim NK cells in CLTs was significantly greater than that in DLTs. There was a negative correlation between the expression of NKG2A on NK cells in the CLT and alkaline phosphatase. Additionally, we analysed IFN-γ, TNF-α, granzyme B, and perforin production in NK cells. There was a significant reduction in IFN-γ production in CLTs compared with DLTs. There is a negative correlation between IFN-γ production levels and NKG2A expression in NK cells from the CLT. The capacity of NKG2A+ NK cells from CLT regions to produce IFN-γ and granzyme B was also significantly decreased. In contrast, the perforin level produced by NKG2A+ NK cells was much greater than that produced by NKG2A− NK cells. We also analysed the correlation between the ratio of the NKG2A expression area in CLT and DLT tissues and the PET–CT value and found a positive correlation between NKG2A expression and the PET–CT value.ConclusionThe increased expression of NKG2A in NK cells induced a reduction in IFN-γ production, and the increased expression of NKG2A may improve lesion activity and fibrosis, which may be helpful for treating hepatic alveolar echinococcosis via immunity.

BACKGROUND:Alveolar and cystic echinococcoses are lethal zoonotic diseases caused by Echinococcus multilocularis and Echinococcus granulosus infections, leading to alveolar echinococcosis (AE) or cystic echinococcosis (CE), respectively. No study has hitherto reported effective treatment approaches for AE or CE with concurrent hepatorenal involvement. AIM:To investigate the feasibility and efficacy of simultaneous combined surgery (SCS) as a comprehensive treatment approach for patients with hepatorenal echinococcosis. METHODS:Clinical datasets of hepatorenal AE (n = 10) and CE (n = 11) patients were retrospectively collected and systematically analyzed. The SCS approach was introduced, and surgical outcomes, complications, and prognoses were documented in detail. RESULTS:The SCS approach incorporated hybridized techniques, including partial hepatectomy, partial or total nephrectomy, ex vivo liver resection and autotransplantation, and total or subtotal cystectomy with endocystectomy. Radical SCS was achieved in 100% of AE patients and 63.6% of CE patients. All surgeries were completed without intraoperative complications. The short-term complication rate was 28.6% (Clavien-Dindo classification: AE-1 IIIb, 3 IIIa; CE-2 II), while the long-term complication rate was 4.8% (Clavien-Dindo classification: AE-1 IIIb). Patients were followed up for a median of 37 months (AE: 6-81 months; CE: 34-123 months), with no reported deaths or disease relapses. CONCLUSION:CS appears to be a feasible and effective treatment method for patients with hepatorenal involvement of AE or CE. It fulfills the management criteria for advanced AE or CE cases, aiming to maximize patient benefits.

BACKGROUND:Neglected tropical diseases (NTDs) and malaria pose a major health challenge, especially in low- and middle-income countries. METHODS:Initially, we performed a descriptive analysis of the Global Burden of Disease (GBD) 2021 database, categorizing data by subtypes. Next, linear regression models were employed to analyze temporal trends. We then utilized four predictive models to forecast the future burden. Additionally, we explored the relationship between estimated annual percentage change (EAPCs) and age-standardized rates (ASRs), as well as Human Development Index (HDI) scores for 2021. Furthermore, decomposition analysis was applied to assess the influence of aging, population dynamics, and epidemiological changes. Lastly, frontier analysis was conducted to examine the connection between disease burden and sociodemographic development. RESULTS:In 2021, NTDs and malaria contributed significantly to the global disease burden, with considerable disparities across genders, age groups, Socio-demographic Index (SDI) regions, GBD regions, and individual countries. From 1990 to 2021, both the number of cases and the associated ASRs have shown a recent downward trend. The EAPCs are positively correlated with ASRs and HDI scores. Projections indicate a continued decline in disease burden through 2046. Additionally, our decomposition analysis highlighted the positive impact of aging and epidemiological shifts on the reduction of the disease burden. Finally, frontier analysis revealed that countries and regions with higher SDI scores have greater potential for further reducing their health burden. CONCLUSION:While the global burden of NTDs and malaria has improved overall, significant disparities remain across regions and countries. Our findings highlight the importance of implementing targeted intervention strategies and maintaining sustained investments to tackle the ongoing challenges.

Liver transplantation (LT) serves as a critical therapeutic intervention for end-stage hepatic echinococcosis. Over time, the emergence of deceased donor LT (DDLT), living donor LT (LDLT), and ex vivo liver resection and autotransplantation (ELRA) has significantly influenced the clinical outcomes of end-stage echinococcosis. All English-language literature on echinococcosis-related LT published in the Web of Science, MEDLINE, and Embase databases from 1980 to 2023 was collected using relevant search terms. Patients' characteristics, surgical features, postoperative complications, mortality, and recurrence rates were systematically analyzed and presented graphically. A total of 44 studies encompassing 476 global echinococcosis patients were analyzed. LT was applied to both male and female patients ranging in age from 10 to 71 years. DDLT and LDLT were primarily indicated for patients with severe hepatic involvement and poor liver function, whereas ELRA was mainly performed in cases with localized lesions, preserved liver function, and a future healthy remnant liver-to-standard liver volume (RLV/SLV) ratio >35%. The major postoperative complication rates were 35.9% (47/131) for DDLT and 30.6% (23/75) for LDLT, both higher than the 23.4% (60/256) rate for ELRA. Overall mortality was highest in DDLT at 27.5% (36/131), compared to 12.0% (9/75) for LDLT and 10.5% (27/256) for ELRA. Recurrence rates were notably higher in DDLT 13.0% (17/131) and LDLT 5.3% (4/75) than in ELRA 0.3% (1/256). LT is a radical treatment option for end-stage alveolar echinococcosis (AE). The need for allotransplantation appears to be decreasing due to early detection and oral benzimidazole administration. Although alternative treatments may be considered, ELRA remains the preferred therapeutic option for end-stage AE patients with adequate remnant liver volume, demonstrating acceptable morbidity and mortality rates. In the future, the widespread adoption of early screening and oral pharmacotherapy is expected to reduce the demand for LT in patients with end-stage disease.