PURPOSE:Placental growth factor (PGF) is associated with the progression of hepatocellular carcinoma (HCC), but current research on this relationship remains limited. This study aims to establish a pathomics model for predicting PGF expression levels in H&E-stained HCC sections, and to explore its prognostic relevance and underlying molecular mechanisms. METHODS:Retrospective analysis utilised H&E images and clinical data from TCGA and an external cohort. Prognostic significance of PGF was assessed via survival analysis. Image segmentation employed the OTSU algorithm, followed by PyRadiomics-based feature extraction. Key features were selected using mRMR and RFE algorithms, with a gradient boosting machine (GBM) model constructed for PGF prediction. Model performance was validated through ROC and Precision-Recall (PR) curves, calibration analysis along with Brier score, and decision curve analysis. Prognostic stratification, Cox regression, and subgroup analyses were conducted for high/low pathomics score (PS: a continuous score derived from a machine learning model based on H&E image features to predict PGF expression) groups. Bioinformatics approaches identified differentially expressed genes (DEGs) and immune infiltration patterns. RESULTS:PGF expression was identified as an independent prognostic factor for poor survival in HCC (HR = 1.922, 95% CI: 1.217-3.036, p = 0.005). A pathomics model integrating seven PGF-associated features demonstrated strong predictive accuracy, achieving an AUC of 0.811 (95% CI: 0.749-0.873) in the training set, 0.747 (95% CI: 0.639-0.855) in the internal validation set, and 0.740 (95% CI: 0.632-0.849) in the external test set. Patients classified into the high-pathomics score (PS) subgroup had significantly poorer survival (HR = 1.667, 95% CI: 1.024-2.713, p = 0.040). Functional analysis of DEGs in high-PS tumours revealed enrichment in ribosome- and coagulation-related pathways, upregulation of the inflammatory gene HBEGF, and increased infiltration of γδT cells. Moreover, TP53 mutations were frequently observed in this subgroup, with a mutation rate exceeding 20%. CONCLUSION:PGF may serve as an independent prognostic biomarker in HCC. The developed pathomics model enables non-invasive PGF expression prediction through H&E image analysis. Mechanistically, PGF-associated molecular alterations involve inflammatory signalling, immune microenvironment remodelling, and frequent TP53 mutations, providing insights into HCC pathogenesis.

Pancreatic adenocarcinoma (PAAD) has an extremely poor prognosis, and existing prognostic markers fail to fully capture the complex heterogeneity of the tumor microenvironment. This study aimed to integrate ligand–receptor (L–R) interactions, multi-omics data, and deep learning-based pathological images to construct an interpretable multimodal prognostic model and to elucidate the mechanisms underlying the cancer-associated fibroblast (CAF) microenvironment. Significant L–R interactions were identified using BulkSignalR, followed by sequential Cox, least absolute shrinkage and selection operator (LASSO)–Cox, and random survival forest analyses to construct a prognostic model. Multi-omics profiling characterized molecular distinctions between risk groups. Key L–R pairs were evaluated with single-cell and spatial transcriptomics, validated in 39 paired clinical specimens via immunofluorescence, and linked to histopathological features through deep learning on hematoxylin and eosin-stained whole-slide images. We identified 236 significant L–R pairs, with 47 associated with prognosis. Integration of LASSO–Cox and random survival forest analyses yielded five key pairs: IL16_KCND1, PLAU_ITGA5, FN1_ITGB3, GNAS_ADCY1, and CALM1_PDE1B. The resulting risk model effectively stratified overall survival. The high-risk group showed higher tumor mutational burden, more frequent KRAS and TP53 mutations, and enrichment of extracellular matrix remodeling, transforming growth factor‑β signaling, and glycolysis pathways. Single-cell and spatial analyses revealed preferential enrichment of PLAU_ITGA5 and FN1_ITGB3 in fibroblast-related compartments. Immunofluorescence confirmed upregulation of these pairs in tumor tissues, and deep learning identified fibroblast-associated histopathological features with strong concordance to the risk axes. This study established the first multimodal prognostic framework integrating L–R interactions and histopathological features, revealing the central role of CAF-mediated L–R signaling in remodeling the PAAD microenvironment and providing a novel strategy for precise prognostic stratification and targeted microenvironmental therapy.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, encompassing a continuum ranging from simple steatosis to steatohepatitis, hepatic fibrosis, and cirrhosis. Despite the complex and heterogeneous pathogenesis, effective therapeutic targets remain elusive. In this study, we sought to identify and validate critical genes implicated in MASLD progression through multi-omics integration and machine learning algorithms. Analysis revealed considerable activation of lipid metabolism, oxidative stress, and inflammation-related pathways throughout disease progression, with notable upregulation of AKR1B10, COL1A2, and SPP1 and downregulation of CYP2C19. These expression patterns were consistently verified across in vivo and in vitro models. Functional assays indicated that AKR1B10 knockdown or CYP2C19 overexpression substantially attenuated hepatocellular lipid accumulation, alleviated oxidative stress and inflammatory responses, and suppressed key lipogenic gene expression. Collectively, these findings elucidate key molecular axes in MASLD progression and provide mechanistic insights and theoretical foundations for the development of targeted therapies.

BACKGROUND:Cysteinyl-tRNA synthetase 1 (CARS1) has been included in ferroptosis-related prognostic signatures, but its clinicopathological relevance, cellular functions, and relationship with the immune microenvironment in hepatocellular carcinoma (HCC) remain incompletely characterized. METHODS:Transcriptomic and clinical data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset were integrated with corresponding data from an institutional HCC tissue cohort of 60 patients. CARS1 expression was evaluated by immunohistochemistry, and immune infiltration was examined using single-sample gene-set enrichment analysis (ssGSEA) and multiplex immunofluorescence, as well as by analyzing public single-cell datasets. The effects of CARS1 depletion were evaluated in MHCC97H and Hep3B cells using Cell Counting Kit-8 (CCK-8) assays, cell-cycle profiling, wound-healing assays, Transwell migration assays, western blotting, and erlotinib-sensitivity assays. RESULTS:CARS1 expression was elevated in HCC and was associated with adverse clinicopathological features and poor overall survival. Quantitative immunohistochemistry confirmed elevated CARS1 protein expression in tumor tissues. CARS1 depletion inhibited cell proliferation, altered cell-cycle distribution, impaired migration, and enhanced in vitro sensitivity to erlotinib. High CARS1 expression was also associated with increased infiltration of Th2-like immune cells. CONCLUSIONS:Elevated CARS1 expression is associated with an adverse biological and immune phenotype in HCC. These clinical, histopathological, and loss-of-function findings support further investigation of CARS1 as a prognostic marker and candidate therapeutic target in HCC, although additional mechanistic and in vivo validation is required.

Background:Belonging to the RNA-binding protein family, Pumilio RNA binding family member 1 (PUM1) modulates gene expression post-transcriptionally through the recognition of particular motifs within the 3' untranslated region of its target transcripts. The present investigation seeks to elucidate PUM1's contribution to HCC pathogenesis and advancement, while also probing the molecular mechanisms that underpin its function. Methods:Publicly available datasets were employed to examine PUM1 transcript abundance in hepatocellular carcinoma, along with its relationship to clinicopathological parameters and prognostic outcomes. PUM1 protein levels were subsequently corroborated in clinical HCC specimens via immunoblotting and immunohistochemical staining. To explore the biological functions of PUM1, we established HCCLM3 cell lines with PUM1 overexpression and knockdown. We then evaluated proliferation via EdU, colony formation, and CCK‑8 assays; apoptosis via TUNEL and flow cytometry; mitochondrial membrane integrity and calcium balance using JC‑1, Mito‑Tracker, and Rhod‑2; and oxygen species (ROS) accumulation via MitoSOX and DCFH‑DA. The downstream molecular pathways were further examined by Western blotting. Results:HCC tissues exhibit markedly upregulated PUM1 levels, a feature tightly correlated with poor prognosis. In vitro, PUM1 preserved mitochondrial membrane integrity and calcium homeostasis in HCC cells, while suppressing the accumulation of reactive oxygen species (ROS). Additionally, PUM1 inhibited programmed cell death and promoted cell proliferation. These biological activities were closely associated with the PI3K-AKT signaling pathway. Conversely, knockdown of PUM1 significantly impaired HCC cell proliferation and induced apoptosis. Conclusion:PUM1 promotes HCC cell proliferation and suppresses mitochondria‑mediated apoptosis, effects that are closely associated with activation of the PI3K-AKT pathway.

BACKGROUND:Mediator complex subunit 10 (MED10) serves as a critical regulator of eukaryotic gene expression by facilitating RNA polymerase II activity. Our investigation aims to characterize MED10's functional contributions and underlying molecular pathways in hepatocellular carcinoma (HCC) development. METHODS:MED10 expression patterns in HCC and their correlation with clinicopathological parameters and patient outcomes were examined using bioinformatics databases and immunohistochemistry. Subsequently, we systematically investigated the biological functions of MED10 in the malignant progression of HCC through comprehensive in vitro experiments, including assessments of cell migration (transwell and wound healing assays), proliferative capacity (cell counting kit-8, colony formation, and 5-Ethynyl-2'-deoxyuridine assays), and cell cycle progression (flow cytometry analysis). Furthermore, we elucidated the underlying molecular mechanisms using real-time quantitative PCR (RT-qPCR), western blotting, immunofluorescence staining, and public database analyses. Furthermore, an in vivo subcutaneous xenograft model was employed to validate MED10's impact on tumor growth. RESULTS:The results revealed a marked increase in MED10 expression levels within HCC tissues, showing a strong association with unfavorable clinical outcomes. Mechanistically, MED10 induced the epithelial-mesenchymal transition (EMT) and enhanced HCC cell migration. Moreover, MED10 overexpression drives HCC cell cycle progression and proliferation by activating rapidly accelerated fibrosarcoma 1 (RAF1), a process potentially mediated through the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK)/cellular myelocytomatosis oncogene (c-Myc) signaling axis. CONCLUSION:MED10 promotes HCC cell migration and EMT but, more importantly, also drives cell cycle progression and proliferation via RAF1 activation, and is related to the MEK/ERK/c-Myc axis.

Early recurrence remains a major challenge in the management of hepatocellular carcinoma (HCC), yet its molecular mechanisms are not fully understood. In this study, we applied an integrative multi-omics strategy at single-cell resolution to explore potential drivers of early HCC recurrence (recurrence time < 2 years) and to develop a predictive framework. By combining single-cell RNA sequencing, proteomics, transcriptomics, and clinical feature analysis, we identified 14 relapse-associated proteins, including CD274, B2M, MYC, and CASP3, as candidate risk factors. Transcriptomic profiling suggested the enrichment of pathways such as MYC-TARGETS-V2 and INTERFERON-GAMMA-RESPONSE. Single-cell analysis indicated reduced immune cell infiltration in recurrent tumors, with myeloid cells (particularly cDC2 and macrophages) showing B2M-associated reprogramming characterized by HLA downregulation and altered GAS6/PROS1 signaling, consistent with tumor-associated macrophage-like phenotypes. A LASSO regression model based on cDC2 and macrophage signature genes demonstrated moderate predictive performance in both the training and validation cohorts (AUC > 0.65). Drug sensitivity analyses further suggested that vandetanib may have the potential to inhibit recurrence by targeting B2M-related pathways. These findings provide evidence that B2M may contribute to remodeling of the immune microenvironment in recurrent HCC. Our integrative single-cell multi-omics approach highlights a possible mechanism of early recurrence and offers a preliminary predictive tool with therapeutic implications.

Background: Since its introduction in 2008, sorafenib has remained the standard first-line systemic treatment for advanced hepatocellular carcinoma (HCC). Nevertheless, its clinical benefits are often compromised by the rapid emergence of drug resistance. This study explores the molecular mechanisms underlying sorafenib resistance, with particular emphasis on the involvement of connective tissue growth factor (CCN2/CTGF) in the regulation of c-Met signaling pathways. Methods: We began by evaluating CCN2 expression levels in HCC tissue samples via immunohistochemistry and analyzing their correlation with clinicopathological characteristics. To functionally characterize CCN2, we established stable HCC cell lines with either knockdown or overexpression of the gene using lentiviral transduction. The effects of CCN2 on cellular proliferation and drug resistance were evaluated using cell counting kit-8 (CCK-8) and colony formation assays. To elucidate the downstream signaling mechanisms, a tyrosine kinase PCR array was employed to identify expression changes within the tyrosine kinase superfamily after CCN2 knockdown. Further investigation into the molecular mechanism by which CCN2 promotes sorafenib resistance was conducted using real-time quantitative PCR (RT-qPCR), western blotting, and immunofluorescence. Finally, the therapeutic potential of co-targeting CCN2 and sorafenib was validated in a nude mouse xenograft tumor model. Results: Our results establish that CCN2 overexpression significantly enhances HCC proliferation, while also inducing resistance to sorafenib. Mechanistically, we identified that CCN2 binds to integrin αV, triggering focal adhesion kinase (FAK) phosphorylation, which in turn promotes yes-associated protein (YAP) nuclear translocation and leads to the transcriptional upregulation of c-Met. This proposed signaling axis was consistently supported by tyrosine kinase PCR array, co-immunoprecipitation, and western blot analyses. Ultimately, in vivo experiments confirmed that simultaneously targeting CCN2 and administering sorafenib produces a synergistic effect, markedly inhibiting tumor growth and restoring therapeutic sensitivity. Conclusion: These results not only elucidate a novel CCN2/FAK/YAP/c-Met axis in sorafenib resistance but also provide a mechanistic rationale for dual-targeting strategies to improve outcomes in advanced HCC.

Patients with malignant biliary obstruction (MBO) are often treated with endoscopic retrograde cholangiopancreatography (ERCP) combined with biliary stent placement for tumor progression. However, certain patients die within 30 days after the procedure, increasing healthcare resource consumption and patient burden. Therefore, the development of early mortality prediction models is important for optimizing treatment decisions. The present study retrospectively analyzed the clinical data of 285 patients with MBO, including demographic information, laboratory indicators and tumor-related factors. Logistic regression and artificial neural network (ANN) models were used to construct a prediction tool, and the model performance was evaluated using area under the curve (AUC), accuracy, sensitivity and specificity. The logistic regression model, which identified the cancer antigen 19-9 (CA19-9) level and a history of previous ERCP surgery as independent risk factors, had an AUC of 0.727 and an accuracy of 65.0%. The ANN model, which combined five variables, namely CA19-9, history of previous ERCP surgery, neutrophil-lymphocyte ratio (NLR), liver metastasis and carcinoembryonic antigen, demonstrated that NLR was the most weighted predictor. Furthermore, the ANN model had an AUC of 0.813, an accuracy of 88.2% and a specificity that was markedly higher than that of the logistic regression model (95.5 vs. 83.3%). However, the ANN model was revealed to be slightly less sensitive compared with the logistic regression model (61.1 vs. 61.2%). In conclusion, compared with logistic regression, the ANN model had a greater performance level in terms of predictive power and specificity, and is suitable for capturing complex non-linear relationships. However, its complexity and risk of overfitting need to be further optimized. The present study provides a new tool for the accurate prediction of the risk of early death after ERCP in patients with MBO, which could help improve individualized treatment strategies.

Primary liver cancer (PLC) and metformin are not well understood to be associated. We conducted a Mendelian randomization (MR) analysis using genetic data from IEU OpenGWAS and FinnGen R10, with metformin as the exposure and PLC as the outcome. The inverse variance weighting (IVW) method was the primary analytical approach, with heterogeneity assessed by Cochran's Q test, pleiotropy by MR-Egger intercept, and outliers by MR-PRESSO. Bioinformatics analyses further explored potential mechanisms, including differential gene expression, protein-protein interactions (PPI), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, immune cell infiltration analysis, and drug sensitivity analysis. MR results demonstrated a significant association between metformin use and reduced risk of PLC (β = -5.6046, OR = 0.0037, p = 0.026), with a Benjamini-Hochberg false discovery rate (FDR) adjusted p value of 0.13. However, no causal effect was observed for hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC). By cross-referencing transcriptome data from the GEO database GSE241466 with metformin-related gene loci, 34 overlapping genes were identified. Differentially expressed genes (DEGs) were filtered using |log2FC| > 0 and p < 0.05, with five hub genes (DDX52, KIF11, GCDH, MRPL45, and TICRR) being particularly prominent. Functional enrichment analysis revealed involvement in cGMP-PKG signaling and fatty acid metabolism pathways. Further validation with GEPIA2, TIMER, and TISCH showed correlations between these genes and immune infiltration, while GSCA-based drug sensitivity analysis suggested therapeutic relevance. In summary, these findings indicate that metformin may reduce PLC risk by modulating metabolic and immune-related pathways, supporting its potential value as an adjunct therapeutic agent. However, further validation through large-scale clinical and basic research is warranted.

Hepatocellular carcinoma (HCC) is one of the most lethal malignant tumors worldwide. Brahma-related gene 1 (BRG1), as a catalytic ATPase, is a major regulator of gene expression and is known to mutate and overexpress in HCC. The purpose of this study was to investigate the mechanism of action of BRG1 in HCC cells. In our study, BRG1 was silenced or overexpressed in human HCC cell lines. Transwell and wound healing assays were used to analyze cell invasiveness and migration. Mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) detection were used to evaluate mitochondrial function in HCC cells. Colony formation and cell apoptosis assays were used to evaluate the effect of BRG1/TOMM40/ATP5A1 on HCC cell proliferation and apoptosis/death. Immunocytochemistry (ICC), immunofluorescence (IF) staining and western blot analysis were used to determine the effect of BRG1 on TOMM40, ATP5A1 pathway in HCC cells. As a result, knockdown of BRG1 significantly inhibited cell proliferation and invasion, promoted apoptosis in HCC cells, whereas BRG1 overexpression reversed the above effects. Overexpression of BRG1 can up-regulate MMP level, inhibit mPTP opening and activate TOMM40, ATP5A1 expression. Our results suggest that BRG1, as an oncogene, promotes HCC progression by regulating TOMM40 affecting mitochondrial function and ATP5A1 synthesis. Targeting BRG1 may represent a new and effective way to prevent HCC development.

目的 探讨PUF家族基因(PUM1、PUM2、PUM3)作为肝癌的潜在预后标志物及其可能的分子调控机制.方法 TCGA数据库分析PUM1、PUM2、PUM3在正常肝组织、癌旁组织和肝癌组织中的表达及差异;Kaplan-Meier曲线分析PUM1、PUM2、PUM3表达与肿瘤患者预后;cBioPortal数据库分析PUM1、PUM2、PUM3在肝癌中的突变情况;String网站及Cytoscape软件构建PUM1、PUM2、PUM3共表达基因的蛋白互作网络;GO/KEGG对PUM1、PUM2、PUM3共表达基因进行功能富集分析;TIMER 2.0 数据库分析PUM1、PUM2、PUM3与肿瘤免疫细胞浸润的相关性.结果 PUM1、PUM2、PUM3 在肝癌组织的表达高于癌旁组织及正常肝组织(P均＜0.001);PUM1、PUM2、PUM3 阳性蛋白表达主要集中于细胞核或细胞质;PUM1 表达与患者年龄、BMI及组织学分级相关(P均＜0.05);PUM2 表达与患者性别、年龄及病理分期相关(P均＜0.05);PUM3 表达与肿瘤T分期及病理分期相关(P均＜0.05);PUM1、PUM2、PUM3 高表达的肝癌患者预后差(P＜0.05);PUMs共表达基因主要富集于RNA剪切、P53 类介质对信号转导的正向调节作用、剪接体组装、转录因子复合体、钙粘蛋白(E-cadherin)结合、P53 结合位点及细胞周期等通路.同时PUM1、PUM2、PUM3表达与辅助性T细胞、中枢记忆性T细胞、辅助性T细胞 2 及嗜酸性粒细胞浸润水平呈正相关关系.结论 PUM1、PUM2、PUM3 在肝癌发生发展过程中发挥重要作用,可作为潜在的分子治疗靶点和预后评价标志物.

Abstract Objective To investigate whether there is an association between immune abnormalities and hepatocellular carcinogenesis in patients with the autoimmune disease systemic lupus erythematosus (SLE), and to explore the possible mechanisms of the association. Methods Based on the mRNA-Seq data of SLE and hepatocellular carcinoma in the public database, we screened the differentially expressed genes using GEO2R, R "Limm" package, and weighted gene co-expression network analysis (WGCNA), respectively, and used random forest tree algorithm to screen out the common genes in both diseases. A random forest(RF) tree algorithm was used to screen out the common genes in the two diseases, to investigate the biological functions of the genes in hepatocellular carcinoma, to construct a nomogram risk prediction model for hepatocellular carcinoma, and to evaluate the predictive efficiency of the model. The immune profile in hepatocellular carcinoma was evaluated based on CIBERSORT and ssGSEA algorithms, and the association of signature genes with the level of tumor immune cell infiltration and the correlation of immune checkpoints in hepatocellular carcinoma were also explored. Results The expression levels of 2 SLE signature genes, CCNB2 and TOP2A, were significantly upregulated in hepatocellular carcinoma, and showed good diagnostic efficacy and clinical prognostic efficacy for hepatocellular carcinoma, suggesting that they may be potential biological targets for hepatocellular carcinoma, and the hepatocellular carcinoma risk prediction model based on the expression levels of CCNB2 and TOP2A showed good risk prediction for hepatocellular carcinoma and has good potential for clinical application. In addition, it was found that the up-regulation of CCNB2 expression may accelerate the G2/M transition of the hepatocellular carcinoma cell cycle, inhibit the apoptotic process, and promote the rate of tumor cell appreciation through the mediation of the p53 signaling pathway, thus contributing to the development and progression of hepatocellular carcinoma. Conclusion The SLE signature genes CCNB2 and TOP2A are potential predictive targets for new-onset hepatocellular carcinoma in SLE patients, and the upregulation of CCNB2 expression may promote hepatocellular carcinoma development and progression through the mediation of the p53 signaling pathway.

Abstract Background: Numerous genetic sequencing projects have demonstrated that alterations in Polε (DNA polymerase epsilon ) due to various causes are associated with the development of multiple human cancers. However, the biological functions of its four core genes, POLE1/2/3/4/, in the occurrence, progression, and prognosis of hepatocellular carcinoma(HCC) remain poorly understood to date. Methods: Multi-omics, multi-level deep mining of HCC data from TCGA and other publicly available databases by using online analysis tools from GEPIA2, TIMER2.0, DAVID, Kaplan-Meier plotter, cBioPortal and MethSurv databases, as well asthe R package to assess Polε family members in HCC for their potential biological functions. Results: We found that the four target genes were significantly upregulated in HCC (P<0.001), their high expression was associated with a lower survival rate (P<0.05), and both diagnostic ROC curves and disease-specific survival time-dependent ROC curves suggested that POLE2/3 showed better disease predictive efficacy, and the four genes were significantly associated with immune infiltration, and drug sensitivity analysis suggested that the high expression groups of four target genes showed higher drug sensitivity in some chemotherapeutic drugs(P<0.001). Conclusion: The POLE1/2/3/4are potential prognostic predictive molecules for HCC and correlate with immune infiltration,and high expression of POLE may serve as a potential predictor of the effect of targeted therapies. POLE2/3 may be the potential diagnostic biomarkers for HCC, and the expression level of POLE3 may serve as a biological predictive target for HCC chemotherapy sensitivity.

Hepatocellular carcinoma (HCC) is a malignant tumor that affects the liver and poses a significant threat to human health. Further investigation is necessary to fully understand the role of SIRT1, a protein linked to tumorigenesis, in HCC development. To investigate the effect of SIRT1 on HCC and elucidate the underlying mechanism. Eight pairs of HCC and paracancerous normal tissue specimens were collected. The levels of SIRT1 and GSDME in tissue samples were assessed using immunohistochemistry and western blotting. SIRT1 levels were determined in HCC (Huh7, HepG2, SNU-423, SNU-398, and HCCLM3) and L-02 cells using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. SNU-423 and HCCLM3 cells were transfected with si-SIRT1 and/or si-GSDME to knock down SIRT1 or GSDME expression. RT-qPCR and western blotting were performed to measure the expression of SIRT1, pro-casp-3, cl-casp-3, GSDME, GSDME-N, PGC-1α, Bax, and cytochrome c (Cyto C). Cell proliferation, migration, invasion, and apoptosis were assessed using the cell counting kit-8 (CCK-8), wound healing assay, Transwell invasion assay, and flow cytometry, respectively. The release of lactate dehydrogenase (LDH) was evaluated using an LDH kit. SIRT1 was upregulated in HCC tissues and cells, and a negative correlation was observed between SIRT1 and GSDME-N. SIRT1 silencing suppressed the proliferation, migration, and invasion of HCC cells while also promoting apoptosis and inducing mitochondrial damage. Additionally, the silencing of SIRT1 resulted in the formation of large bubbles on the plasma membrane of HCC cells, leading to cellular swelling and aggravated GSDME-dependent pyroptosis, resulting in an increase in LDH release. Inhibition of GSDME reduced SIRT1 silencing-induced cell swelling, decreased LDH release rate, and promoted apoptosis. SIRT1 silencing promotes GSDME-dependent pyroptosis in HCC cells by damaging mitochondria.

Abstract Objective To investigate the activation of hepatic embryonic stem cell factor in hepatocellular carcinoma and its characteristic effect on hepatocellular carcinoma. Methods Based on mRNA-seq data of hepatocellular carcinoma and matched clinical data in the TCGA database, and mRNA-seq data of hepatic embryonic stem cell genes screened by laboratory sequencing, we used the R package and some online analysis tools to find activated hepatic embryonic stem cell genes in hepatocellular carcinoma, and used support vector machine (SVM) and LASSO regression analysis to further screen out significantly differentially expressed hepatic embryonic stem cell genes, and to investigate their functional characteristics and clinical significance in hepatocellular carcinoma based on the expression of these hepatic embryonic stem cell genes. Finally, the expression of five embryonic stem cell factors in HCC tissues was detected based on immunohistochemical methods. Results Five liver embryonic stem cell genes, TYW3/CKLF/P2RY6/TUBA1B and RSU1 were significantly upregulated in hepatocellular carcinoma, showed good diagnostic efficacy for hepatocellular carcinoma, and were significantly associated with a poorer survival prognosis of patients. The prognostic model based on the five hepatic embryonic cell genes showed good predictive efficacy and has good potential for clinical application, immunohistochemical expression validation results also showed high expression of TYW3/CKLF/P2RY6/TUBA1B, and RSU1 in HCC, and were highly expressed in HCC and mainly expressed in the cytoplasm. Conclusion The activation of five hepatic germ cell genes, TYW3/CKLF/P2RY6/TUBA1B, and RSU1 are important diagnostic targets and prognostic markers for hepatocellular carcinoma, which significantly correlated with patient clinical prognosis. And the prognostic model of HCC based on TYW3/CKLF/P2RY6/TUBA1B, and RSU1 has a good clinical application potential for hepatocellular carcinoma.

AimsSplenectomy combined with pericardial devascularization is one of the important methods to treat hypersplenism, gastrointestinal bleeding, and other complications caused by liver cirrhosis; however, it is accompanied by a high risk of portal vein thrombosis (PVT). This study aimed to explore the preventive and therapeutic effects of proximal splenic vein ligation (PSVL) with postoperative transcatheter anticoagulant therapy (TCAT) on PVT. MethodsThis study retrospectively selected 143 patients with liver cirrhosis and portal hypertension, who received splenectomy combined with pericardial devascularization from June 30, 2018 to June 30, 2021. According to computed tomography photography, within 1 week before the operation, the patients were divided into a prevention group (without preoperative PVT, n = 112) and a treatment group (preoperative PVT, n = 31). Then, each group was subdivided based on the treatment and prevention measures into PSVL + TCAT (n = 70) and systemic anticoagulant therapy (SAT) subgroups (n = 73). The preventive and therapeutic effects of PSVL followed by TCAT on PVT were analyzed. ResultsThe operation time in the PSVL + TCAT subgroups was longer than that in the SAT subgroups (185 +/- 76 min vs. 161 +/- 55 min; p < 0.01). There was no difference between the two subgroups in terms of operative bleeding (345 +/- 82 mL vs. 336 +/- 65 mL; p > 0.50). There was no operative death, and all patients recovered uneventfully. In the prevention group, procedure-related complications occurred in two patients in the PSVL + TCAT subgroup (3.7% [2/54]), including one patient with slight pancreatitis and one patient with chylous leakage, owing to mobilization of the pancreas. The PVT incidence in the prevention group was significantly different between the two subgroups at postoperative 7th day, 3rd month, and 6th month (PSVL + TCAT: 0%, 11.1%, and 5.6% vs. SAT: 39.7%, 31.0%, and 20.7%, respectively; all p < 0.05). In the treatment group, the thrombus regression rate at postoperative 7th day and disappearance rates at the 3rd month and the 6th month of the PSVL + TCAT subgroup were significantly higher than those in the SAT subgroup after anticoagulant and thrombolysis therapy (PSVL + TCAT: 75.0%, 68.8%, and 87.5% vs. SAT: 20.0%, 26.7%, and 40.0%; all p < 0.05). ConclusionsPSVL + TCAT reduces the risk of PVT after splenectomy and is safe and effective in treating PVT during surgery for portal hypertension.

Objective To investigate the effect of COVID-19 infection on pancreatic cancer. Methods Based on the mRNA-Seq data of COVID-19 patients and pancreatic cancer (PC) patients in the GEO database, we used a support vector machine (SVM), LASSO-Cox regression analysis and random forest tree (RF) to screen the common signature genes of the two diseases and further investigate their effects and functional characteristics on PC, respectively. The above procedures were performed in R software. Results The proteins COL10A1/FAP/FN1 were found to be common signature genes for COVID-19 and PC, were significantly up-regulated in both diseases and showed good diagnostic efficacy for PC. The risk model based on COL10A1/FAP/FN1 showed good PC risk prediction ability and clinical application potential. Tumor typing based on COL10A1/FAP/FN1 expression levels effectively classified PC into different subtypes and showed significant differences between the two subtypes in terms of survival prognosis, immune levels, immune checkpoint expression levels, mutation status of common tumor mutation sites, and drug sensitivity analysis. While pathway analysis also revealed that FN1 as an extracellular matrix component may be involved in the biological process of PC by regulating the PI3K-AKT signaling axis. Conclusion The upregulated expression of COL10A1/FAP/FN1, the characteristic genes of COVID-19, are potential diagnostic targets for PC, and the upregulated expression of FN1 may promote the progression of PC by activating the PI3K-AKT signaling pathway. The COL10A1/FAP/FN1-based typing provides a new typing approach for PC, and also provides a good reference and idea for the refinement of PC treatment and subsequent clinical research.

目的 探讨腹腔镜下经Glisson蒂鞘外横断式解剖性肝切除术的可行性及技术要点.方法 收集 2019年 3 月至 2021 年 12 月宁夏医科大学总医院肝胆外科收治的 40 例行肝切除术的患者,16 例在全腹腔镜下行鞘外Glisson蒂横断式解剖性肝切除术(腹腔镜组),24 例行传统开腹肝切除术(开腹组),比较两组患者术中及术后临床指标及并发症发生情况.结果 两组患者均顺利完成手术,腹腔镜组顺利完成全腹腔镜下鞘外Glisson蒂横断式解剖性肝切除,其中左半肝切除 2 例、左外叶切除 9 例、右前叶S5 段切除 2 例、右后叶S6 段切除 2 例、右后叶S7 段 1 例,无中转开腹,患者未发生术后肝脏断面出血等并发症.腹腔镜组除手术时间比开腹组长(P＜0.05),出血量、输注红细胞、血浆量、腹腔引流管拔除的时间、住院时间等差异均无统计学意义(P均＞0.05).腹腔镜组术后胃肠减压管拔除时间及术后进食时间均短于开腹组(P均＜0.05),两组患者术后并发症差异无统计学意义(P＞0.05).结论 全腹腔镜下鞘外Glisson蒂横断式肝切除术可安全、有效控制腹腔镜下肝切除时术中的出血,快速解决边界难以确定及切除范围等问题,推荐用于腹腔镜下肝脏疾病解剖性肝切除术.