Liver resection is the primary curative treatment for early-stage hepatocellular carcinoma (HCC); however, high recurrence rates remain a major challenge in the absence of effective prognostic and preventive strategies. Here, we identified surgery-induced C-C motif chemokine ligand 11 (CCL11) as a pivotal driver of HCC recurrence through dual mechanisms of immunosuppression and tumor invasiveness. Elevated postoperative circulating CCL11 levels correlated strongly with HCC recurrence and poorer survival, and their integration with clinical parameters enhanced the predictive accuracy of HCC recurrence. Mechanistically, hepatic injury-induced CCL11 recruited immunosuppressive CCR5+CD206+ M2-like macrophages into the residual liver. These macrophages exhibited enhanced PD-L1 expression via activation of the CCL11/IKK/IκB/NF-κB1 axis and promoted regulatory T cell (Treg) induction from naïve CD4+ T cells. Concurrently, CCL11-CCR3 signaling in HCC cells activated PI3K/AKT/MafK to upregulate MMP13, enhancing the invasion ability of HCC cells. In orthotopic models, CCL11 enrichment increased tumor burden and extrahepatic metastases, while post-resection anti-CCL11 therapy reduced HCC recurrence and extended the survival rate of tumor-bearing mice. Our findings unveil CCL11 as a master regulator of the pro-tumorigenic niche post-resection, driving recurrence through coordinated immune evasion and promoting tumor invasiveness. Targeting the CCL11-CCR5/CCR3 axis presents a promising strategy to improve HCC surgical outcomes.

With the rising incidence of chronic liver disease and a persistent imbalance between organ supply and demand, expanded criteria donors (ECD)are gaining recognition. High-risk donor livers, meeting ultra-long criteria, are increasingly utilized to bridge the gap between organ demand and supply. For these high-risk livers, dynamic preservation through machine perfusion can mitigate post-transplant complications by enhancing graft quality and enabling viability testing prior to transplantation. Ex situ machine perfusion has overcome the limitations of traditional static cold preservation, transforming liver transplantation by reducing ischemia-reperfusion injury, offering a continuous assessment of organ quality, and optimizing the use of marginal grafts, thereby expanding the donor liver pool. This review summarizes current clinical applications and classifications of machine perfusion devices and explores potential future strategies for assessing the viability of marginal livers, therapeutic interventions, and organ function modulation post-recovery.

Nanosecond pulsed electric field (nsPEF) ablation enables non-thermal tumor destruction with favorable tissue selectivity, but its long-term efficacy is often limited by postoperative recurrence. Here, we developed an electroporation-primed, tumor microenvironment-responsive core-shell cascade nanoparticle, ZnO2-NiFc@MSCU (ZNFM), to potentiate nsPEF-mediated hepatocellular carcinoma (HCC) therapy and induce durable antitumor immunity. ZNFM contains a degradable ZnO2 core that releases Zn2+ and generates H2O2, together with an acid-responsive NiFc shell that catalyzes H2O2 into cytotoxic reactive oxygen species, thereby enhancing local tumor eradication. Meanwhile, the incorporated prodrug MSCU, generated by conjugating the STING agonist MSA-2 with curcumin, undergoes esterase-triggered hydrolysis in tumor cells to co-release both agents. Mechanistically, Zn2+ potentiates STING activation, whereas curcumin promotes immunogenic cell death and alleviates immunosuppression by inhibiting the IDO-kynurenine axis. Importantly, nsPEF pretreatment serves as a delivery primer that markedly enhances intratumoral penetration and cellular uptake of ZNFM, thereby strengthening local therapeutic activation and promoting systemic antitumor immunity. In HCC models, nsPEF + ZNFM induces marked tumor regression, promotes dendritic cell maturation, elicits robust cytotoxic T-cell responses, and suppresses tumor rechallenge. These findings establish an electroporation-enabled cascade nanotherapeutic platform for durable HCC chemoimmunotherapy.

Tumor-responsive materials are useful in delivering immunotherapeutics, but they still lack inherent activity to increase the immunogenicity of the tumor and to promote immune cell infiltration, which are challenges faced by tumor immunotherapy. Here, we present a versatile chitosan hydrogel with multi-functions such as pH-responsiveness, injectability, self-healing property, and ability to induce anti-tumor immune response. This hydrogel was prepared simply by mixing chitosan with a boronated crosslinker incorporating the anti-tumor agent nordihydroguaiaretic acid (NDGA). It responsively releases NDGA in acidic tumor conditions, inducing immunogenic cell death (ICD), stimulating dendritic cell maturation, and enhancing T cell infiltration. In a hepatocellular carcinoma model, intratumoral injection of this hydrogel not only destroyed tumor cells but also augmented tumoricidal immune responses, effectively inhibiting tumor progression. This work demonstrates the proof-of-concept for developing responsive hydrogels with intrinsic immunostimulatory effects, offering the potential to enhance the effectiveness of tumor immunotherapy.

INTRODUCTION:To explore the role of age at listing on outcomes for patients with acute-on-chronic liver failure (ACLF) awaiting liver transplantation (LT). MATERIALS AND METHODS:We assessed adult candidates listed for LT in the Scientific Registry of Transplant Recipients database from January 1, 2007 to June 30, 2018. Patients were divided into four groups based on age at listing: I (≤34), II (35-49), III (50-64), and IV (≥65). The ACLF grade was estimated (est-ACLF), and intent-to-treat survival, overall survival (OS), as well as potential predictors for OS was evaluated. RESULTS:Est-ACLF-3 was associated with a higher 30-d cumulative dropout rate and inferior intent-to-treat survival across age groups. No difference was observed in OS among ACLF grades in group I, but significantly inferior OS was observed in higher ACLF grades in groups II-IV. Multivariate analysis showed age (P < 0.001, ref. group I; hazard ratio 0.995 for group II, P = 0.936; 1.196 for group III, P = 0.002; 1.651 for group IV, P < 0.001) and est-ACLF grade (P < 0.001, ref. est-ACLF-0; 1.214 for est-ACLF-1, P < 0.001; 1.246 for est-ACLF-2, P < 0.001; 1.578 for est-ACLF-3, P < 0.001) were independent predictors for OS. Generalized additive model showed different association between age and OS among different ACLF grades. CONCLUSIONS:Young patients with high ACLF grades could achieve similar OS compared with those with low grades. Elderly patients with higher ACLF grades were associated with inferior outcomes after LT.

Purpose:Circadian disruption contributes to hepatocellular carcinoma (HCC) progression. This study aimed to develop a CT-based radiomics model to non-invasively predict circadian rhythm (CR) gene expression profiles for improved prognostic assessment. Methods:Mendelian randomization (MR) analysis revealed a significant causal association between CR disorders and the risk of HCC. In Cohort 1 (TCGA database, n = 424), 32 CR-related genes were identified from an initial set of 71 genes. Univariate Cox regression analysis identified 18 prognosis-related genes, and a risk model containing 8 genes was constructed using LASSO and multivariate Cox regression. This model was then validated in Cohort 2 (ICGC database, n = 232). The gene CRTC2 was further validated in vitro. Radiomics features were constructed based on enhanced CT images from Cohort 3 (TCIA database, n = 45) to predict CR risk genes, and the prognostic value of the model was validated in Cohort 4 (The Fourth Affiliated Hospital of Zhejiang University School of Medicine, n = 38). Results:The CR risk gene model stratified patients into high- and low-risk groups with significantly different survival outcomes in both TCGA and ICGC cohorts (TCGA: P < 0.001; ICGC: P = 0.029). The risk score was independently associated with overall survival (HR = 3.582, 95% CI: 2.101-6.107, P < 0.001). Experimental results confirmed that knockdown of CRTC2 significantly inhibited HCC cell proliferation, migration, invasion, and induced apoptosis. The radiomics model achieved an AUC of 0.931 in the training set and 0.760 in the validation set for predicting CR gene expression. Importantly, in the clinical validation cohort, patients with low radiomics scores had significantly longer survival (P = 0.039). Conclusion:Circadian rhythm-related gene expression, implicated in HCC development, can be non-invasively predicted via CT-based radiomics. The proposed model offers promise for prognostic stratification and personalized treatment planning in HCC.

Background: Zinc finger C3H1-type containing (ZFC3H1) might regulate RNA processes. However, research lacks the prognostic value of ZFC3H1 in hepatocellular carcinoma (HCC). Methods: The study analyzed ZFC3H1 expression in HCC cells and its correlation with patient prognosis using transcriptomics, immunohistochemistry, and quantitative real-time reverse transcription PCR, as well as single-cell RNA expression data. Additionally, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were used to investigate the potential ZFC3H1-related cellular functions and signaling pathways. The impact of ZFC3H1 expression on the tumor microenvironment and tumor mutational burden (TMB) was assessed using the ESTIMATE algorithm. Cell-based assays, including cell counting kit 8, proliferation, colony formation, cell cycle, wound healing, and Transwell assays, were conducted to evaluate the influence of ZFC3H1 on hepatocellular carcinoma proliferation and migration. Results: ZFC3H1 is upregulated in HCC and linked to tumor progression. High ZFC3H1 expression is a prognostic risk factor for HCC, according to Kaplan-Meier and Cox regression analyses. ESTIMATE analysis suggested that ZFC3H1 reduces immune cell infiltration and increases the TMB. Patients with low ZFC3H1 expression might respond better to immunotherapy. High ZFC3H1 expression is associated with increased half-maximal inhibitory concentration (IC50) of sorafenib. Functional experiments demonstrated that reducing ZFC3H1 expression inhibited HCC cell proliferation and migration. Conclusion: ZFC3H1 is upregulated in HCC, promoting the proliferation and migration of liver cancer cells, impacting the prognosis of HCC patients and the effectiveness of immunotherapy. ZFC3H1 might serve as a therapeutic target and biomarker for HCC.

Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumors (PNETs), remains one of the deadliest malignancies in gastrointestinal oncology. PDAC is characterized by late diagnosis, rapid progression, and limited resectability, with only 20

Liver transplantation is the only effective method for end-stage liver disease; however, liver ischemia reperfusion injury (IRI) seriously affects donor liver function after liver transplantation. IRI is a pathophysiological process in which organ damage is aggravated after the blood flow and oxygen supply of ischemic organ tissues are restored. It combines the two stages of hypoxic cell stress triggered by ischemia and inflammation-mediated reperfusion injury. Herein, we studied the protective effect and mechanism of the anti-T cell Ig and mucin domain (TIM1) monoclonal antibody, RMT1-10, on hepatic cell injury induced by IRI. First, a liver IRI model was established in vivo. HE, TEM, and Tunel were used to detect liver tissue injury, changes in the liver ultrastructure and liver cell apoptosis, respectively. ELISA were performed to determine the levels of ALT, AST, MDA, GSH, and related inflammatory factors. We found that RMT1-10 could significantly reduce liver injury. Flow cytometry results showed that the number of TIM1+ regulatory B cells (Bregs) in the IRI liver increased briefly, while pretreatment with RMT1-10 could increase the number of TIM1+ Bregs and interleukin-10 (IL-10) secretion in liver IRI model mice, thus playing a protective role in liver reperfusion. When Anti-CD20 was used to remove B cells, RMT1-10 had a reduced effect on liver IRI. Previous data showed that the number of T helper 1 cells (Th1:CD4+; CD8+) increased significantly after IRI. RMT1-10 inhibited Th1 cells; however, it significantly activated regulatory T cells. Sequencing analysis showed that RMT1-10 could significantly downregulate the expression of nuclear factor-kappa B (NF-κB) pathway-related genes induced by IRI. These results suggested that RMT1-10 could promote the maturation of B cells through an atypical NF-κB pathway, thereby increasing the number of TIM1+ Bregs and associated IL-10 secretion to regulate the inflammatory response, thereby protecting against liver IRI.

Background: Mesenchymal cells, including hepatic stellate cells (HSCs), fibroblasts (FBs), myofibroblasts (MFBs), and vascular smooth muscle cells (VSMCs), are the main cells that affect liver fibrosis and play crucial roles in maintaining tissue homeostasis. The dynamic evolution of mesenchymal cells is very important but remains to be explored for researching the reversible mechanism of hepatic fibrosis and its evolution mechanism of hepatic fibrosis to cirrhosis. Methods: Here, we analysed the transcriptomes of more than 50,000 human single cells from three cirrhotic and three healthy liver tissue samples and the mouse hepatic mesenchymal cells of two healthy and two fibrotic livers to reconstruct the evolutionary trajectory of hepatic mesenchymal cells from a healthy to a cirrhotic state, and a subsequent integrative analysis of bulk RNA sequencing (RNA-seq) data of HSCs from quiescent to active (using transforming growth factor β1 (TGF-β1) to stimulate LX-2) to inactive states. Results: We identified core genes and transcription factors (TFs) involved in mesenchymal cell differentiation. In healthy human and mouse livers, the expression of NR1H4 and members of the ZEB families (ZEB1 and ZEB2) changed significantly with the differentiation of FB into HSC and VSMC. In cirrhotic human livers, VSMCs transformed into HSCs with downregulation of MYH11, ACTA2, and JUNB and upregulation of PDGFRB, RGS5, IGFBP5, CD36, A2M, SOX5, and MEF2C. Following HSCs differentiation into MFBs with the upregulation of COL1A1, TIMP1, and NR1H4, a small number of MFBs reverted to inactivated HSCs (iHSCs). The differentiation trajectory of mouse hepatic mesenchymal cells was similar to that in humans; however, the evolution trajectory and proportion of cell subpopulations that reverted from MFBs to iHSCs suggest that the mouse model may not accurately reflect disease progression and outcome in humans. Conclusions: Our analysis elucidates primary genes and TFs involved in mesenchymal cell differentiation during liver fibrosis using scRNA-seq data, and demonstrated the core genes and TFs in process of HSC activation to MFB and MFB reversal to iHSC using bulk RNA-seq data of human fibrosis induced by TGF-β1. Furthermore, our findings suggest promising targets for the treatment of liver fibrosis and provide valuable insights into the molecular mechanisms underlying its onset and progression.

The prevalence of alcohol-related hepatocellular carcinoma (HCC) has been increasing during the last decade. Cancer research requires cell lines suitable for both in vitro and in vivo assays. However, there is a lack of cell lines with a high in vivo metastatic capacity for this HCC subtype. Herein, a new HCC cell line was established, named HCC-ZJ, using cells from a patient diagnosed with alcohol-related HCC. The karyotype of HCC-ZJ was 46, XY, del (p11.2). Whole-exome sequencing identified several genetic variations in HCC-Z that occur frequently in alcohol-associated HCC, such as mutations in TERT, CTNNB1, ARID1A, CDKN2A, SMARCA2, and HGF. Cell counting kit-8 assays, colony formation assays, and Transwell assays were performed to evaluate the proliferation, migration, and sensitivity to sorafenib and lenvatinib of HCC-Z in vitro. HCC-ZJ showed a robust proliferation rate, a weak foci-forming ability, a strong migration capacity, and a moderate invasion tendency in vitro. Finally, the tumorigenicity and metastatic capacity of HCC-Z were evaluated using a subcutaneous xenograft model, an orthotopic xenograft model, and a tail-veil injection model. HCCZJ exhibited strong tumorigenicity in the subcutaneous xenograft and orthotopic tumor models. Moreover, HCC-ZJ spontaneously formed pulmonary metastases in the orthotopic tumor model. In summary, a new HCC cell line derived from a patient with alcohol-related HCC was established, which showed a high metastatic capacity and could be applied for in vitro and in vivo experiments during pre-clinical research.Highlights• An alcohol-related HCC cell line, HCC-ZJ, was established• HCC-ZJ was applicable for in vitro functional experiment and gene editing• HCC-ZJ was applicable for in vivo tumor growth and spontaneous metastasis models.

Single-cell RNA sequencing (scRNA-seq) is a key technology for investigating cell development and analysing cell diversity across various diseases. However, the high dimensionality and extreme sparsity of scRNA-seq data pose great challenges for accurate cell type annotation. To address this, we developed a new cell-type annotation model called scGAA (general gated axial-attention model for accurate cell-type annotation of scRNA-seq). Based on the transformer framework, the model decomposes the traditional self-attention mechanism into horizontal and vertical attention, considerably improving computational efficiency. This axial attention mechanism can process high-dimensional data more efficiently while maintaining reasonable model complexity. Additionally, the gated unit was integrated into the model to enhance the capture of relationships between genes, which is crucial for achieving an accurate cell type annotation. The results revealed that our improved transformer model is a promising tool for practical applications. This theoretical innovation increased the model performance and provided new insights into analytical tools for scRNA-seq data.

Background Functional performance as measured by the Karnofsky Performance Status (KPS) scale has been linked to the outcomes of liver transplant patients; however, the effect of KPS on the outcomes of the hepatocellular carcinoma (HCC) liver transplant population has not been fully elucidated. We aimed to investigate the association between pre-transplant KPS score and long-term outcomes in HCC patients listed for liver transplantation. Methods Adult HCC candidates listed on the Scientific Registry of Transplant Recipients (SRTR) database from January 1, 2011 to December 31, 2017 were grouped into group I (KPS 80–100%, n = 8,379), group II (KPS 50–70%, n = 8,091), and group III (KPS 10–40%, n = 1,256) based on percentage KPS score at listing. Survival was compared and multivariable analysis was performed to identify independent predictors. Results Patients with low KPS score had a higher risk of removal from the waiting list. The 5-year intent-to-treat survival was 57.7% in group I, 53.2% in group II and 46.7% in group III ( P < 0.001). The corresponding overall survival was 77.6%, 73.7% and 66.3% in three groups, respectively ( P < 0.001). Multivariable analysis demonstrated that KPS was an independent predictor of intent-to-treat survival ( P < 0.001, reference group I; HR 1.19 [95%CI 1.07–1.31] for group II, P = 0.001; HR 1.63 [95%CI 1.34–1.99] for group III, P < 0.001) and overall survival( P < 0.001, reference group I; HR 1.16 [95%CI 1.05–1.28] for group II, P = 0.004; HR 1.53 [95%CI 1.26–1.87] for group III, P < 0.001). The cumulative 5-year recurrence rates was higher in group III patients (7.4%), compared with 5.2% in group I and 5.5% in group II ( P = 0.037). However, this was not significant in the competing regression analysis. Conclusions Low pre-transplant KPS score is associated with inferior long-term survival in liver transplant HCC patients, but is not significantly associated with post-transplant tumor recurrence.

Purpose:Nonsense-mediated RNA decay (NMD), a surveillance pathway for selective degradation of aberrant mRNAs, is associated with cancer progression. Its potential as a predictor for aggressive hepatocellular carcinoma (HCC) is unclear. Here, we present an innovative NMD risk model for predicting HCC prognosis.Methods:The Cancer Genome Atlas (TCGA) data of 374 liver HCC (LIHC) and 50 normal liver samples were extracted. A risk model based on NMD-related genes was developed through least absolute shrinkage and selection operator Cox (LASSO-Cox) regression of the LIHC-TCGA data. Prognostic validation was done using GSE54236, GSE116174, and GSE76427 data. Univariate and multivariate Cox regression analyses were conducted to assess the prognostic value of the model. We also constructed nomograms for survival prediction. Tumor immune infiltration was evaluated using the CIBERSORT algorithm, and the tumor cell phenotype was assessed. Finally, mouse experiments verified UPF3B knockdown effects on HCC tumor characteristics.Results:We developed a risk model based on four NMD-related genes (PABPC1, RPL8, SMG5, and UPF3B) and validated it using GSE54236, GSE116174, and GSE76427 data. The model effectively distinguished high- and low-risk groups corresponding to unfavorable and favorable HCC outcomes. Its prognostic prediction accuracy was confirmed through time-dependent ROC analysis, and clinical-use nomograms with calibration curves were developed. Single-cell RNA sequencing results indicated significantly higher expression of SMG5 and UPF3B in tumor cells. Knockdown of SMG5 and UPF3B inhibited HCC cell proliferation, invasion, and migration, while affecting cell-cycle progression and apoptosis. In vivo, UPF3B knockdown delayed tumor growth and increased immune cell infiltration.Conclusion:Our NMD-related gene-based risk model can help identify therapeutic targets and biomarkers for HCC. Additionally, it assists clinicians in predicting the prognosis of HCC patients.

Introduction and objectives This study aimed to investigate the association between biological aging and liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Materials and methods We analyzed NHANES 2017–2020 data to calculate phenotypic age. Hepatic steatosis and fibrosis were identified using controlled attenuation parameters (CAP), fatty liver index (FLI) and transient elastography (TE). The odds ratios (ORs) and 95 % confidence intervals (CI) for significant MASLD fibrosis were calculated using multivariate logistic regression, and subgroup analyses were performed. We explored the potential causal relationship between telomere length and liver fibrosis using Mendelian randomization (MR). Additionally, we used the expression quantitative trait loci (eQTL) method and GSE197112 data to identify genes related to liver fibrosis and senescence. Finally, the APOLD1 expression was validated using GSE89632. Results Phenotypic age was associated with liver fibrosis occurrence in MASLD (OR = 1.08, 95 % CI 1.05–1.12). Subgroup analyses by BMI and age revealed differences. For obese or young to middle-aged MASLD patients, phenotypic age is significantly associated with liver fibrosis. (OR = 1.14, 95 % CI 1.10–1.18; OR = 1.07, 95 % CI 1.01–1.14 and OR = 1.14, 95 % CI 1.07–1.22). MR revealed a negative association between telomere length and liver fibrosis (IVW method: OR = 0.63288, 95 % CI 0.42498–0.94249). The gene APOLD1 was identified as a potential target through the intersection of the GEO dataset and eQTL genes. Conclusions This study emphasized the link between biological aging and fibrosis in young to middle-aged obese MASLD patients. We introduced phenotypic age as a clinical indicator and identified APOLD1 as a potential therapeutic target.

Background/Aims: Liver transplantation is the most effective treatment for the sickest patients with acute-on-chronic liver failure (ACLF). However, the influence of donor age on liver transplantation, especially in ACLF patients, is still unclear. Methods: In this study, we used the data of the Scientific Registry of Transplant Recipients. We included patients with ACLF who received liver transplantation from January 1, 2007, to December 31, 2017, and the total number was 13,857. We allocated the ACLF recipients by age into group I (donor age ≤17 years, n=647); group II (donor age 18-59 years, n=11,423); and group III (donor age ≥60 years, n=1,787). Overall survival (OS), graft survival, and mortality were compared among the three age groups and the four ACLF grades. Cox regression was also analyzed. Results: The 1-, 3-, and 5-year OS rates were 89.6%, 85.5%, and 82.0% in group I; 89.4%, 83.4%, and 78.2% in group II; and 86.8%, 78.4%, and 71.4% in group III, respectively (p<0.001). When we analyzed the different effects of donor age on OS with different ACLF grades, in groups II and III, we observed statistical differences. Finally, the cubic spline curve told us that the relative death rate changed linearly with increasing donor age. Conclusions: Donor age is related to OS and graft survival of ACLF patients after transplantation, and poorer results were associated with elderly donors. In addition, different donor ages have different effects on recipients with different ACLF grades.

Liver transplantation (LT) is the most effective way to save patients with acute-on-chronic liver failure (ACLF). However, the impact of donor diabetes mellitus (DM) on LT outcomes in patients with ACLF has not been fully investigated.We retrospectively analyzed data from the Scientific Registry of Transplant Recipients (SRTR) between January 1st, 2008 to December 31st, 2017 in this study. All the patients were divided into donors with DM and without DM group (DM: 1,394; non-DM: 11138). We compared the overall survival (OS) and graft survival (GS) across different estimated ACLF (estACLF) grades between two groups.There were 25.10% estACLF-3 patients in the entire cohort. And in estACLF-3 patients, 318 patients had DM donors. The estACLF-3 associated 5-year OS rate in the non-DM group was 74.6%, significantly better than that in the DM group, with corresponding survival rate at 64.9% (P < 0.001). Donor DM was an independent predictor for OS in the entire cohort as well as in estACLF-3 patients.Donor DM was associated with inferior outcomes of LT in patients with estACLF-3. However, the differences were not obvious in recipients with other estACLF grades.

Most cases of hepatocellular carcinoma (HCC) are able to be diagnosed through regular surveillance in an identifiable patient population with chronic hepatitis B or cirrhosis. Nevertheless, 50% of global cases might present incidentally owing to symptomatic advanced-stage HCC after worsening of liver dysfunction. A systematic search based on PUBMED was performed to identify relevant outcomes, covering newer surveillance modalities including secretory proteins, DNA methylation, miRNAs, and genome sequencing analysis which proposed molecular expression signatures as ideal tools in the early-stage HCC detection. In the face of low accuracy without harmonization on the analytical approaches and data interpretation for liquid biopsy, a more accurate incidence of HCC will be unveiled by using deep machine learning system and multiplex immunohistochemistry analysis. A combination of molecular-secretory biomarkers, high-definition imaging and bedside clinical indexes in a surveillance setting offers a comprehensive range of HCC potential indicators. In addition, the sequential use of numerous lines of systemic anti-HCC therapies will simultaneously benefit more patients in survival. This review provides an overview on the most recent developments in HCC theranostic platform.

It is a challenging clinical task to determine how to repair large-area skin defects better. Traditional wound dressings (e.g., cotton and gauze) can only be used as a dressing; consequently, there is an increasing demand for wound dressings with additional properties (i.e., antibacterial and pro-repair) in clinical practice. In this study, a composite hydrogel with o-nitrobenzene-modified gelatin-coated decellularized small intestinal submucosa (GelNB@SIS) was designed for the repair of skin injuries. SIS is a natural extracellular matrix with a 3D microporous structure and also contains high levels of growth factors and collagen. GelNB provides this material photo-triggering tissue adhesive property. The structure, tissue adhesion, cytotoxicity, and bioactivity to cells were investigated. Based on in vivo study and histological analysis, we found the combination of GelNB and SIS improved the healing process by promoting vascular renewal, dermal remodeling, and epidermal regeneration. Based on our findings, GelNB@SIS is a promising candidate for tissue repair applications.

BackgroundNASH-related liver transplants are increasing because of the obesity epidemic, but the influence of T2DM on various levels of BMI among NASH recipients is unclear.Research design and methodsWe analyzed data retrieved from SRTR on 4,515 patients. We divided patients by BMI into five groups: normal weight; overweight; class 1 obesity; class 2 obesity; and class 3 obesity. Statistical analysis was done.ResultsPatients in the NASH group with T2DM had a lower patient and graft survival than patients without T2DM (5-year patient and graft survival: 77.5% vs. 79.8%; P = 0.001 and 76.4% vs. 78.2%; P = 0.002, respectively). Multivariate Cox proportional regression showed an independent association between T2DM and decreased patient and graft survival (HR, 1.170; P = 0.015 and HR, 1.133; P = 0.048, respectively). In the lean and the class 3 obesity NASH groups, patients with T2DM had lower patient and graft survival than the patients without T2DM. In the class 3 obesity NASH group, T2DM was independently associated with decreased patient survival (HR, 1.581; P = 0.027).ConclusionOur research reveals that the focus of the post-transplantation treatment should be different for different BMI patients.