Abstract:The Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), first developed by Professor Hans Schlitt from Germany in 2007, combines the ligation of the portal vein branches of the tumor-bearing lobe and separation of the tumor-bearing lobe from the healthy lobe at the same time during the first stage, allows for rapid regeneration of the healthy lobe within 1-2 weeks. Once the healthy liver lobe has grown sufficiently, the tumor-bearing lobe is removed in the second stage of operation, which provides an opportunity for radical resection for a significant portion of patients with liver cancer initially considered unresectable. ALPPS has remarkable efficacy inducing more rapid liver regeneration than traditional portal vein embolization. Furthermore, with the accumulation of surgical experience and refinements in surgical techniques, the postoperative complication rate of ALPPS has significantly decreased. As a result, it is increasingly being applied in the treatment of primary and secondary liver tumors, including colorectal liver metastases, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma. Since its inception, ALPPS has undergone continuous clinical modifications, such as advancements in basic surgical techniques and skills, minimally invasive hepatic partition, minimally invasive portal vein ligation, minimally invasive surgical approaches, and rescue ALPPS using transcatheter arterial embolization. During the liver regeneration induced by ALPPS, significant changes can occur in the hepatic immune microenvironment. However, the roles of key immune components, spatial origin, distribution, and subpopulation characteristics during liver regeneration remain to be clarified. The specific effects and mechanisms of ALPPS on liver tumors are not fully understood and require further exploration and confirmation. The clinical application prospects of ALPPS are promising, and research on related mechanisms may offer new insights into the active induction of liver regeneration and the prevention and treatment of liver function failure.

Abstract:Background and Aims Three-dimensional (3D) visualization technology utilizes computers to reconstruct 3D images from CT and/or MRI examination, which provides an intuitive and clear display of the morphology and spatial distribution of structures such as the liver, pancreas, bile ducts, blood vessels, and tumors. This technology is of great significance in clarifying anatomical variations of the liver vascular system, accurately calculating future liver reserve, and aiding in surgical planning. This study was performed to assess the clinical value of preoperative liver 3D visualization assessment in the surgical treatment of patients with China liver cancer (CNLC) stageⅡ-Ⅲa hepatocellular carcinoma (HCC).Methods The clinical data of patients with CNLC Ⅱ-Ⅲa HCC who underwent surgical treatment in the Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, between 2015 and 2017, were retrospectively analyzed. Based on their preoperative evaluation method, patients were classified into the conventional radiological and 3D visualization evaluation groups. Kaplan-Meier analysis was used to compare the two groups' postoperative recurrence-free survival (RFS) and overall survival (OS). Univariate and multivariate Cox regression analyses were performed to determine relevant risk factors affecting the prognosis of patients.Results A total of 110 patients with CNLC Ⅱ-Ⅲa HCC undergoing surgical treatment were included in the study, with 74 patients in the conventional radiological evaluation group and 36 patients in the 3D visualization evaluation group. There were no statistically significant differences between the two groups regarding sex, age, hepatitis B surface antigen, α-fetoprotein, Child-Pugh classification, tumor diameter, tumor number, macrovascular invasion, CNLC stage, prophylactic interventional therapy, and adjuvant targeted therapy (all P>0.05). The 90-d mortality rates were 2.8% (1/36) in the 3D visualization evaluation group and 4.1% (3/74) in the conventional radiological evaluation group, with no statistically significant difference (P>0.05). Kaplan-Meier survival analysis demonstrated that both OS and RFS in the 3D visualization evaluation group were significantly superior to those in the conventional radiological evaluation group (P=0.024; P=0.014). Multivariate Cox regression analysis revealed that preoperative 3D visualization assessment was an independent protective factor for OS and RFS (P=0.015; P=0.010).Conclusion Preoperative 3D visualization assessment can significantly improve the prognosis of patients with intermediate and advanced HCC undergoing surgical treatment. It has good application value in the surgical treatment of intermediate and advanced HCC and is recommended to be further explored and promoted.

Abstract:Background and Aims The utilization of laser ablation (LA) has improved the precision of liver tumor ablation, thereby reducing the possibility of complications, and has become an important clinical treatment method for malignant liver tumors. However, there are few reports on the application of three-dimensional (3D) reconstruction-assisted laparoscopic ultrasound-guided LA in the treatment of malignant liver tumors. Therefore, this study was performed to evaluate the clinical efficacy and application value of 3D reconstruction-assisted laparoscopic ultrasound-guided LA in the treatment of malignant liver tumors.Methods The clinical data of patients with malignant liver tumors who underwent 3D reconstruction-assisted laparoscopic ultrasound-guided LA from September 2020 to March 2022 were retrospectively collected. The completion of the surgery, operative time, intraoperative blood loss, occurrence of postoperative complications, changes in liver function parameters and tumor markers before and after surgery, as well as the tumor overall response rate (ORR) and recurrence rate during the postoperative follow-up period, were analyzed.Results A total of 35 patients who met the inclusion criteria were included, including 25 cases of primary liver cancer, 6 cases of colorectal cancer liver metastasis, 2 cases of pancreatic cancer liver metastasis, and 2 cases of lung cancer liver metastasis. All patients successfully completed the surgery, with an operative time of (66.3±2.8) min and an intraoperative blood loss of (15.9±12.4) mL. Three patients experienced mild postoperative complications, including 1 case of pleural effusion and 2 cases of postoperative fever, without severe perioperative complications or deaths. The patients showed elevated transaminase and total bilirubin levels after surgery, but after routine liver protection treatment, the levels returned to preoperative levels within one month. In the 25 cases of primary liver cancer, the postoperative AFP level was significantly lower than the preoperative level at 3 months (8.2 ng/mL vs. 5.3 ng/mL, Z=-3.269, P=0.001). All patients underwent contrast-enhanced CT at 3 months postoperatively, showing a ORR of 100%. At 6 months postoperatively, a repeat contrast-enhanced CT scan revealed that 2 out of 53 treated lesions showed local recurrence, resulting in a local recurrence rate of 3.8% (2/53). These lesions were subsequently treated with repeat LA.Conclusion Selective use of 3D reconstruction-assisted laparoscopic ultrasound-guided LA for malignant liver tumors has the advantages of precise treatment, minimal invasiveness, and satisfactory efficacy. In particular, for small lesions in the liver that are difficult to locate, those near important structures, and other complex situations, choosing this treatment method is beneficial for patients.

Abstract:Background and Aims Liver transplantation has become increasingly crucial in treating liver cancer. However, the clinical issue of tumor recurrence and metastasis after transplantation remains unresolved. This study aimed to analyze the relationship between interleukin 34 (IL-34) expression and the prognosis, tumor recurrence, and metastasis in liver cancer transplant recipients. It also aimed to explore its role in the growth and metastasis of liver cancer.Methods The expression of preoperative serum IL-34 of 93 liver cancer transplant recipients was detected using the ELISA method. Statistical methods were used to analyze the relationship between IL-34 expression and clinicopathologic characteristics and prognosis. The diagnostic value of IL-34 in detecting tumor recurrence and metastasis was analyzed using the receiver operating characteristic (ROC) curve. Human hepatocellular carcinoma orthotopic xenograft models were established in male 5-6-week-old NOD/SCID mice, which were randomly divided into four groups and intraperitoneally injected with different concentrations of IL-34 (5, 10, 35 μg/kg) or an equal amount of saline (control group) once daily for a total of two weeks. After ten weeks, the overall survival rate, tumor volume and mass, and lung tissue metastasis of the mice in each group were compared. Western blot was used to detect the expression of cell proliferation-related proteins (Ki-67 and PCNA), tumor metastasis-related proteins (MMP-2 and MMP-9), and epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, vimentin, and snail) in the transplanted tumors of each group.Results After a 5-year follow-up, among the 93 liver cancer transplant recipients, 27 cases experienced tumor recurrence, 9 cases experienced metastasis, and 45 cases died. The expression levels of IL-34 in patients with tumor recurrence or metastasis were significantly lower than those without tumor recurrence or metastasis (both P<0.05). Low expression of IL-34 was negatively correlated with tumor recurrence, metastasis, and vascular invasion (all P<0.05). The 5-year overall survival rate and tumor-free survival rate of patients with low IL-34 expression were significantly lower than those with high IL-34 expression (both P<0.05). Low expression of IL-34 and tumor recurrence and metastasis were independent risk factors for overall survival (all P<0.05). The area under the curve (AUC) for serum IL-34 in detecting tumor recurrence and metastasis was 0.93 and 0.79, respectively, superior to AFP. Compared with the control group, the overall survival rate of mice in the three IL-34 intervention groups increased, tumor volume and weight decreased, lung tissue metastasis rate and number of metastatic lesions decreased, and the expression levels of Ki-67, PCNA, MMP-2, MMP-9, vimentin, and snail proteins in the transplanted tumors decreased. In contrast, the expression level of E-cadherin increased, all of which showed a concentration-dependent relationship (all P<0.05).Conclusion Low expression of serum IL-34 is closely associated with adverse prognosis, tumor recurrence, and metastasis in liver cancer transplant recipients. IL-34 inhibits the growth and metastasis of liver cancer, possibly through the inhibition of cell proliferation and EMT.

Abstract:Background and Aims There is currently no definitive clinical consensus regarding the treatment of metachronous liver metastasis after radical resection of pancreatic ductal adenocarcinoma (PDAC). Therefore, this study was performed to compare the efficacy of liver resection (LR) and microwave ablation (MWA) for the treatment of metachronous hepatic oligometastasis following PDAC resection in order to provide reference guidelines for the clinical management of these patients.Methods The clinicopathologic data of 74 patients with metachronous hepatic oligometastasis after PDAC radical resection, treated between January 2014 and December 2021 at Meishan People's Hospital, were retrospectively collected. Among them, 37 patients underwent LR (LR group), 28 patients received MWA (MWA group), and 9 patients received only palliative chemotherapy (conservative treatment group, compared with the former two groups for survival benefits). Based on clinical follow-up data, the postoperative complications and long-term efficacy were compared between the LR and MWA groups, and risk factors for the long-term efficacy of PDAC patients were analyzed.Results There were no statistically significant differences in baseline characteristics between the LR and MWA groups (all P>0.05). The median overall survival (OS) in the LR and MWA groups was 25.0 months (95% CI=21.5-28.5) and 23.0 months (95% CI=19.2-26.8), respectively, while the conservative treatment group had a median OS of 11.0 months (95% CI=8.9-13.1). The median progression-free survival (PFS) in the LR and MWA groups was 17.0 months (95% CI=14.7-19.3) and 15.0 months (95% CI=11.7-18.3), respectively. Survival curve comparisons showed no statistically significant differences in OS rate and PFS rate between the LR and MWA groups (χ²=0.184, P=0.668; χ²=0.488, P=0.485). There was no statistically significant difference in recurrence rate between the two groups (70.3% vs. 78.6%, χ²=0.569, P=0.451), but the LR group had a significantly higher incidence of severe postoperative complications compared to the MWA group (48.6% vs. 14.3%, χ²=8.405, P=0.004). The LR group also had a significantly longer hospital stay than that of the MWA group (9.0 d vs. 5.0 d, P<0.001). Cox multivariate regression analysis indicated that perioperative chemotherapy omission and early liver metastasis (<1 year) were independent risk factors for poor prognosis in PDAC patients (both P<0.05).Conclusion LR and MWA are effective treatments for metachronous liver metastasis after PDAC resection, with similar long-term efficacy. However, MWA is associated with fewer severe postoperative complications and shorter hospital stays. Poor prognosis is observed in PDAC patients who do not receive perioperative chemotherapy and experience early liver metastasis (<1 year).

Abstract:Background and Aims Spontaneous liver cancer rupture and hemorrhage is a severe complication. For the treatment of spontaneous rupture and hemorrhage of liver cancer, the preferred approach is rapid hemostasis using a simple and effective method, followed by further treatment when the overall and local conditions allow, to save the patient's life and extend their survival. This study aims to investigate the clinical value of sequential hepatectomy and intraperitoneal hyperthermic chemotherapy (HIPEC) in spontaneous rupture and hemorrhage of liver cancer.Methods A retrospective analysis was conducted on clinical data of 102 patients with spontaneous rupture and hemorrhage of liver cancer admitted to the Hepatobiliary Surgery Department of Yuxi People's Hospital between May 1, 2013, and December 1, 2021. Among them, 48 patients underwent hepatectomy with sequential HIPEC (observation group), while 54 underwent simple hepatectomy (control group). Relevant clinical variables were compared between the two groups of patients.Results There were no statistically significant differences between the two groups in terms of general preoperative information, major surgical parameters, postoperative pathology, length of hospital stay, postoperative drainage tube retention time, the incidence of Clavien-Dindo grade 2 or above complications, perioperative mortality and reoperation rate after recurrences (all P>0.05). The observation group showed higher total hospitalization costs, a higher postoperative cumulative disease-free survival rate and overall survival rate than the control group (both P<0.05).The observation group had a significantly lower incidence of peritoneal seeding metastasis than the control group (all P<0.05).Conclusion Sequential hepatectomy and HIPEC can reduce the incidence of peritoneal seeding metastasis in liver patients with spontaneous rupture and hemorrhage, improve postoperative disease-free survival rate and overall survival rate, and serve as a safe and effective treatment modality with significant clinical value. However, it is associated with higher costs.

Abstract:Background and Aims Immunotherapy is emerging as a new systemic treatment method for patients with hepatocellular carcinoma (HCC), with its clinically recognized therapeutic effects. However, imaging evaluation methods for assessing treatment response are still being explored. Imaging assessment is crucial in providing sufficient evidence for determining the primary clinical endpoints of immunotherapy in clinical practice. This study analyzes and compares the efficacy evaluation of immunotherapy in HCC using the Immune-Related Response Evaluation Criteria in Solid Tumors (iRECIST) and the modified Response Evaluation Criteria in Solid Tumors (mRECIST), aims to find a more suitable imaging assessment method for immunotherapy efficacy in HCC and facilitate the development of individualized and precise treatment plans by clinical physicians.Methods A retrospective analysis of clinical data from HCC patients who received PD-L1 monoclonal antibody immunotherapy at the First Affiliated Hospital of the Army Medical University from 2017 to 2021 was conducted. Of the patients, 58 were males, and 9 were females. Clinical imaging data from CT or MRI dynamic contrast-enhanced scans were collected at three time points: one week before treatment and two and four months after treatment initiation. The efficacy evaluations were performed using both iRECIST and mRECIST criteria, and the differences in the evaluation results between the two criteria were compared.Results Evaluation of immunotherapy efficacy using iRECIST and mRECIST criteria two and four months after PD-L1 monoclonal antibody treatment showed statistically significant differences (P<0.01). The main discrepancy between the two evaluation methods was observed in the objective response rate (ORR), with mRECIST showing a significantly higher ORR compared to iRECIST (P<0.01). Many patients who were classified as achieving complete or partial response using mRECIST were categorized as stable diseases according to iRECIST. Both evaluation methods indicated that approximately 50% of patients initially classified as progressive disease continued treatment and achieved stable or partial response status.Conclusion The mRECIST criteria, which measure "viable tumor" while excluding necrotic areas, provide a more objective and scientific approach to evaluate treatment efficacy. This approach prevents underestimation of treatment effects caused by significant tumor burden reduction despite minor changes in tumor size. On the other hand, iRECIST criteria propose concepts of unconfirmed and confirmed disease progression, making them more suitable for unique responses observed during immunotherapy, such as pseudo-progression. Therefore, it is recommended to adopt the mRECIST criteria for assessing "viable tumor" while considering the cyclic reevaluation model of iRECIST criteria to reassess patients initially classified as a progressive disease under mRECIST after the next treatment cycle to avoid premature treatment termination and potentially provide more clinical benefits to patients, as well as to offer guidance for clinicians to make subsequent treatment plans.

Abstract:Background and Aims Hepatocellular carcinoma (HCC) is a common cause of cancer-related mortality. Studies have shown that long non-coding RNAs (lncRNAs) regulate the expression of microRNAs (miRNAs), which, in turn, participate in tumorigenesis and progression by inhibiting target mRNA translation or promoting mRNA degradation. LINC00313 is a cancer-promoting lncRNA that contributes to tumor development and progression. Annexin A2 (ANXA2) is upregulated in various malignant tumors, including HCC, promoting a malignant phenotype, and it may be regulated by upstream miR-342-3p. This study was conducted to explore the expression of LINC00313, miR-342-3p, and ANXA2 in HCC cells and their interrelationships.Methods The expressions of LINC00313, miR-342-3p, and ANXA2 were assessed in human liver tissue cells and HCC cell lines (Li-7, HuH-7, Hep3B2.1-7) using qRT-PCR and Western blot. Li-7 cells were cultured in vitro and divided into different groups: control (untreated), LINC00313 siRNA group (transfected with LINC00313 siRNA), miR-342-3p mimics group (transfected with miR-342-3p mimics), negative control co-transfection group (transfected with negative siRNA and negative miRNA), and co-transfection group (transfected with LINC00313 siRNA and miR-342-3p inhibitor). The expressions of LINC00313, miR-342-3p, and ANXA2 were analyzed in these groups using qRT-PCR and Western blot. Cell proliferation was assessed using MTT assay and colony formation assay. Apoptosis was detected by TUNEL staining. Transwell invasion assay and Western blot were performed to evaluate cell invasion and expressions of epithelial-mesenchymal transition-related proteins (vimentin and E-cadherin), respectively. Immunofluorescence staining was used to determine the Bax/Bcl-2 ratio in the cells. Dual-luciferase reporter assay was conducted to analyze the regulatory relationship between LINC00313 and miR-342-3p and between miR-342-3p and ANXA2 in Li-7 cells. Furthermore, a xenograft tumor model in nude mice was established to validate the impact of LINC00313 knockdown on Li-7 cell growth in vivo.Results Compared to human liver tissue cells, the expressions of LINC00313 as well as ANXA2 mRNA and protein was significantly upregulated in Li-7, HuH-7, and Hep3B2.1-7 cells, while miR-342-3p expression was significantly downregulated (all P<0.05). Compared to the control group, the LINC00313 siRNA group and miR-342-3p mimics group showed significant reductions in ANXA2 mRNA and protein expressions, cell proliferation, colony formation, and invasion, as well as decreased vimentin protein expression (all P<0.05). Furthermore, miR-342-3p expression, apoptosis rate, E-cadherin protein expression, and Bax/Bcl-2 ratio were significantly increased in these groups (all P<0.05). When compared to the LINC00313 siRNA group, the co-transfection group exhibited elevated ANXA2 mRNA and protein expressions, increased cell proliferation, colony formation, and invasion, as well as enhanced vimentin expression. However, it reduced miR-342-3p expression, apoptosis rate, E-cadherin protein expression, and Bax/Bcl-2 ratio (all P<0.05). In Li-7 cells, LINC00313 could negatively regulate miR-342-3p expression, while miR-342-3p could negatively regulate ANXA2 expression (both P<0.05). In vivo experiments demonstrated that compared to untreated Li-7 cell xenografts, LINC00313 knockdown in Li-7 cells significantly reduced tumor volume and mass. Additionally, LINC00313 and ANXA2 mRNA and protein expression in tumor tissues were markedly decreased, while miR-342-3p expression was significantly increased (all P<0.05).Conclusion LINC00313 is upregulated in HCC cells and may promote a malignant phenotype by inhibiting miR-342-3p, thereby increasing the expression of its target gene, ANXA2, in HCC cells.

Abstract:Background and Aims Acetaminophen (APAP) is a safe and effective antipyretic, analgesic, and anti-inflammatory drug. However, excessive use of APAP can rapidly induce acute liver injury and liver failure, leading to patient death or the need for liver transplantation. Studies have shown that macrophages are essential in maintaining liver homeostasis and regulating the progression of acute and chronic liver injuries. Therefore, this study investigated the role and mechanisms of macrophage functional changes in APAP-induced acute liver injury.Methods Male BALB/c mice were randomly divided into the control group (gavage with normal saline), drug-induced liver injury model group (APAP group, 600 mg/kg APAP gavage), and drug-induced liver injury model plus macrophage depletion agent clodronate liposomes (CL) group (APAP+CL group, intravenous injection of CL 12 h before APAP gavage). After 3 h of APAP gavage, serum and liver tissue samples were collected from each group of mice. The serum levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured. Liver tissue pathological changes were observed, and the levels of reactive oxygen species (ROS) and heme oxygenase-1 (HO-1) expression in the liver tissue were detected. RAW246.7 cells were cultured with APAP or APAP plus HO-1 inhibitor zinc protoporphyrin Ⅸ (ZnPPⅨ) using untreated RAW246.7 cells as a control. Then, the changes in cellular ROS levels and HO-1 expression were observed.Results The results of the animal experiment showed that compared to the control group, the APAP group exhibited significant pathological changes in the liver, with significant increases in serum levels of ALP, ALT, and AST, as well as elevated levels of ROS and HO-1 expression in liver tissue. However, in the APAP+CL group, these changes were significantly suppressed, and the differences in all quantitative indicators were statistically significant (all P<0.05). The cell experiment results showed that ROS levels and HO-1 expression in RAW246.7 cells were significantly increased after incubation with APAP. However, when co-incubated with ZnPPⅨ, the APAP-induced ROS levels and HO-1 expression elevation were significantly inhibited (all P<0.05).Conclusion APAP may promote macrophage ROS generation by inducing HO-1 expression, causing acute liver injury. Intervention targeting this pathway may provide a new approach to preventing and treating clinical acute liver injury.

Abstract:Background and Aims Previous studies have found a close association between intrahepatic immune regulation and the development of liver fibrosis. However, the key genes associated with immune cells in liver fibrosis are still unclear. Therefore, this study aimed to investigate the correlation between key genes in liver fibrosis, disease progression, and the distribution of intrahepatic immune cells.Methods Differential gene expression analysis was performed on RNA sequencing data (RNA-seq) from liver tissues with different degrees of liver fibrosis obtained from public databases (GSE162694 and GSE49541), using normal liver samples as controls. The relative expression order (REO) algorithm was used to identify relative reversal stabile pairs. Key genes associated with liver fibrosis were analyzed. A CCl₄-induced mouse model of liver fibrosis was established, and histopathological changes were identified using Masson staining. The mRNA and protein expression of key genes were detected using qRT-PCR and Western blot methods, respectively. The relationship between key genes and immune cells as well as the progression of liver fibrosis was analyzed using the xCell tool.Results Analysis of the sequencing data identified two overlapping reverse gene pairs associated with liver fibrosis (THBS2>RHDE and LBH>LRRC19). Both THBS2 and LBH were upregulated in liver fibrosis tissues, and the expression of LBH was significantly correlated with fibrosis stage, histological score, and inflammation score (all P<0.05). Compared to the control group, the mRNA and protein levels of LBH in the liver of the model mice were significantly upregulated (both P<0.05). Based on the median expression value of LBH, the samples from the liver fibrosis datasets GSE162694 and GSE49541 were divided into the LBH high-expression group and the LBH low-expression group. The xCell analysis revealed that CD4⁺ memory T cells, central memory CD8⁺ T cells, dendritic cells, aDC, cDC, and other immune cells were enriched and immune cell scores were significantly upregulated in the high LBH expression group (all P<0.05).Conclusion The transcriptional co-factor LBH may regulate the distribution of intrahepatic immune cells and promote the progression of liver fibrosis.

Abstract:Background and Aims Hepatocellular carcinoma (HCC) is characterized by high invasiveness, frequent recurrence, and poor clinical prognosis. The molecular mechanisms underlying the occurrence and development of HCC remain unclear. Phosphatidylinositol transfer protein cytoplasmic 1 (PITPNC1) is a lipid metabolism-related gene shown to promote cancer. However, the role of PITPNC1 in the development of HCC remains unknown. Thus, this study aimed to investigate the expression and function of PITPNC1 in HCC.Methods A prospective cohort study was conducted on 116 patients with HCC who underwent liver resection surgery at Xiangya Hospital, Central South University, from January 2015 to December 2018. Patient medical records and tissue specimens were collected, and regular follow-ups were performed. Immunohistochemistry was used to detect PITPNC1 protein expression in patient tissue samples, and the relations of PITPNC1 expression with clinicopathologic features and prognosis were analyzed. The expression of PITPNC1 in human HCC cell lines was analyzed using the LCCLD database. Lentivirus-mediated small RNA interference was utilized to silence PITPNC1 expression in the highly invasive and metastatic HCC cell line MHCC97H. Colony formation and subcutaneous tumor experiments were performed to observe the relationship between PITPNC1 expression and HCC growth, and Oil Red O staining was conducted on the subcutaneous xenografts. Bioinformatics analysis was used to investigate the molecular mechanisms of PITPNC1 action.Results The PITPNC1 protein was positively stained in the cytoplasm, with a positive expression rate of 76.7% (88/116) in tumor tissues and 21.5% (24/116) in adjacent non-tumor liver tissues, and the difference was statistically significant (P<0.001). High PITPNC1 expression was significantly associated with satellite nodules (P=0.041), vascular invasion (P<0.001), tumor differentiation (P=0.027), BCLC stage (P=0.009), and TNM stage (P=0.028). Kaplan-Meier survival analysis revealed that HCC patients with high PITPNC1 expression had significantly lower overall survival (OS) and recurrence-free survival (RFS) rates (both P<0.001); PITPNC1 expression was an independent factor influencing OS and RFS (HR=11.775, 95% CI=1.462-4.082, P=0.006; HR=1.928, 95% CI=1.306-4.889, P=0.004). After PITPNC1 silencing, both in vitro and in vivo growth of MHCC97H cells were significantly suppressed (both P<0.05). Oil Red O staining showed a significant reduction in lipid accumulation in the subcutaneous xenografts following PITPNC1 downregulation (P<0.05). Database analysis indicated that PITPNC1 overexpression was associated with lipid metabolism-related PPAR signaling pathway activity.Conclusion PITPNC1 is a novel oncogene and adverse prognostic marker in HCC. It may play a significant role in promoting HCC growth by regulating the lipid metabolism pathway.

Abstract:Background and Aims Patients with advanced liver cirrhosis often experience a series of complications, leading to an increased risk of death. Therefore, early identification of high-risk patients for liver cirrhosis mortality is of significant clinical importance. In this study, we used the H2O platform and automated machine learning (AutoML) framework to develop a predictive model for 30-d in-hospital mortality in liver cirrhosis patients, aiming to provide new methods for improving patient prognosis and clinical management of liver cirrhosis.Methods General information and laboratory examination data were collected from hospitalized liver cirrhosis patients at Jintan Hospital affiliated with Jiangsu University and Hunan Provincial People's Hospital. Multiple machine learning algorithm models for mortality outcomes were established using the H2O AutoML framework. ROC curves were plotted, and confusion matrices were used to evaluate the performance of the models. Furthermore, important variables were visualized.Results The best model, gradient boosting machine (GBM), had a Gini value of 0.994, R² of 0.775, and LogLoss of 0.120. Important variables in the model included prothrombin time, creatinine, white blood cells, and age. The SHAP feature graph and partial dependence graph demonstrated the correlation between important variables and the overall predictions of the model. LIME visualization showed the individual predictive effects of the variables. The best GBM model had a specificity of 0.950, sensitivity of 0.676, and AUC of 0.793 in the validation set, outperforming four algorithm models (XGBoost, Logistic regression, random forest, and deep learning), as well as the MELD and ALBI scores.Conclusions The established machine learning model for predicting short-term mortality provides an effective tool for screening the risk of short-term death in patients with liver cirrhosis. However, its reliability still needs further evaluation through external validation from multiple centers.

Abstract:Hepatocellular carcinoma (HCC) is the most prevalent pathological type of primary liver cancer, accounting for 75% to 85% of all liver cancer cases. The occurrence and development of HCC are closely associated with the regulatory functions of both coding RNAs and non-coding RNAs. Circular RNAs (circRNAs) represent a novel class of endogenous non-coding RNA. CircRNAs are covalently closed-loop RNA formed by back-splicing of precursor mRNAs. Compared to linear RNAs, circRNAs lack the 5'-end cap and 3'-end poly A tail structure but can regulate gene expression in mammals. CircRNAs are structurally conserved and stable and have a higher tolerance to exonucleases. In HCC, circRNAs have been demonstrated to regulate tumor cell proliferation, migration, invasion, and resistance to cell death. Their roles in regulating angiogenesis, genomic instability, immune surveillance, and metabolic reprogramming are also becoming evident. However, the detailed mechanisms involving circRNAs in HCC remain elusive, especially regarding how circRNAs regulate angiogenesis in HCC, modulate the evasion of HCC cells from the detection and attack of the immune cells, and regulate cellular energy metabolism to provide energy for HCC cell proliferation, invasion, and metastasis. Studying circRNAs that play critical regulatory roles in HCC may hold promise for targeted therapies, thereby enhancing treatment effectiveness and improving patient prognosis. In this review, the authors summarize the abnormal expression of circRNAs in HCC and their regulatory roles in angiogenesis, immune cell interactions, and energy metabolism for HCC cells.

Abstract:Currently, the main challenge faced by the global organ transplantation field is the shortage of donors. Due to a severe imbalance between the demand for recipients and the number of standard donors, surgeons have shifted their focus to donation after cardiac death (DCD). Compared to donation after brain death (DBD), DCD faces the major issue of experiencing a longer warm ischemia time (WIT), leading to an increased rate of postoperative complications in patients, particularly biliary complications. Controlled donation after cardiac death (cDCD) refers to a planned withdrawal of life-sustaining treatments following the wishes of the patients or their families. After a period of "no contact" (usually 5 min), the patient is declared permanently deprived of cerebral circulation while rapid organ recovery is performed. Since the transplantation of DCD donors preserved using conventional organ preservation methods is not satisfactory, the advantages of the normothermic perfusion technique have become increasingly evident during transplantation in recent years, garnering attention from surgeons and scientists. Unlike living liver transplantation and DBD liver transplantation, removing the transplant from a DCD donor is impossible before death is pronounced. However, during normothermic regional perfusion (NRP), surgeons can block blood flow to the brain after death is declared and initiate warm perfusion of the donor organ using extracorporeal membrane oxygenation. It restores the function of the donor liver in the donor body, allowing the liver to produce bile and remove lactate. This process provides valuable time to monitor and optimize the indicators of the donor's liver before it leaves the donor and is transplanted. Several clinical studies have already demonstrated that using NRP as an in-situ organ repair technique can yield transplantation outcomes for cDCD donor livers comparable to those of DBD donors. Additionally, some researchers have developed various combinations of perfusion techniques, including the use of NRP in conjunction with machine perfusion (MP) and dual hypothermic oxygenated machine perfusion (D-HOPE), all of which have shown promising transplantation results, offering more possibilities for liver transplant donor preservation. While many consider NRP a method of obtaining more high-quality organs, some scholars have raised ethical concerns about this technique. They argue that it violates the rules of donation after death and that the procedures involved in NRP perfusion may lead to the patient's death. Therefore, ensuring that the patient's circulation and respiration are irreversibly lost and that brain circulation is absent during NRP is particularly crucial. Given the importance of NRP in the field of transplantation, the authors provide a summary of the application of NRP techniques in cDCD.

Abstract:The Hippo signaling pathway, initially discovered as a pathway that inhibits tissue growth in Drosophila, is mainly composed of three kinase cascades: MST1/2, LATS1/2, and Yap/TAZ. As research progressed, homologous genes of the Hippo signaling pathway were also identified in mammals, and they play a critical role in controlling organ size and other physiological functions. The Hippo signaling pathway mainly exerts its effects by regulating the nuclear translocation of Yap. When the upstream kinases of the Hippo signaling pathway are inactivated, Yap/TAZ becomes dephosphorylated and can enter the cell nucleus as a transcriptional co-activator, where it interacts with specific transcription factors to exert its effects. Previous studies on the Hippo-Yap signaling pathway have mainly focused on cell fate, metabolism, tumorigenesis, and the immune system. As research continues to deepen and the incidence of liver diseases increases, significant progress has been made in understanding the role of the Hippo signaling pathway in the occurrence and development of liver diseases. In this context, the authors discuss the involvement of the Hippo-Yap signaling pathway in various clinically common liver diseases, including cholestatic liver injury, liver ischemia-reperfusion injury, non-alcoholic fatty liver disease, alcoholic liver disease, acetaminophen-induced liver injury, liver fibrosis, and liver cancer.

Abstract:Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease that can progress to cirrhosis and liver cancer, is a serious global health concern. NAFLD is strongly linked to metabolic factors and is a major hepatic manifestation of the metabolic syndrome, often accompanied by obesity, diabetes, cardiovascular disease, and other metabolic disorders. To more accurately reflect its pathogenesis, in 2020, the International Liver Panel renamed NAFLD as metabolic-associated fatty liver disease (MAFLD). So far, there is no clear theoretical explanation for its pathophysiological mechanism, which is typically characterized by excessive lipid accumulation in hepatocytes. With hepatocellular damage and fibrosis development, NAFLD will gradually progress to end-stage liver disease. The treatment of early-stage NAFLD mainly advocates dietary and lifestyle changes. Pharmacological treatments for NAFLD mainly target key pathogenic processes and related metabolic disorders, but specific drugs are still insufficient. The prevalence of obesity-related NAFLD and NAFLD-related end-stage liver disease has been steadily rising. These patients do not respond to dietary changes and exercise or cannot achieve weight loss through lifestyle modifications, leading to disease exacerbation. As a result, surgical treatment has become a new option for such patients. Bariatric surgery can improve liver histology, reduce transaminase levels, and the incidence of cardiovascular disease. Common surgical methods include sleeve gastrectomy (SG), adjustable gastric banding (ABG), and Roux-en-Y gastric bypass (RYGB), among which SG is the most commonly used surgical procedure for patients with NAFLD-related cirrhosis. However, bariatric surgery also has some limitations, including the degree of patient tolerance, the technical level of the operator, and the occurrence of perioperative complications, which need to be carefully considered. Its clinical efficacy and safety must be further studied to make it suitable for NAFLD patients. Liver transplantation is the only possible cure for patients with NAFLD-related end-stage liver disease. In recent years, with the mature development of transplantation technology and immunosuppressants, liver transplantation has made considerable achievements in treating end-stage liver disease. However, there are still many problems in the treatment of NAFLD patients. The use of marginal donor liver, the prolongation of the isohepatic phase, the evaluation and management before transplantation, and the recurrence after transplantation all affect the graft and patient survival rates. This article mainly reviews the general situation, general treatment, and surgical treatment progress of NAFLD to provide reference for clinical work.

Abstract:背景与目的 多囊肝（PLD）属一种罕见遗传性疾病，早期一般无特殊临床症状，随其病程进展可以导致肝肾功能衰竭。归纳PLD的病因、发病机制、临床特征，对指导PLD诊治有重要的临床参考价值。笔者报告1例Schnelldorfer D型PLD合并多囊肾（PKD）患者诊治过程，并结合文献对病例特点进行总结，以期加深对该病的认识。方法 回顾性分析川北医学院附属医院肝胆外科收治的1例PLD合并PKD患者的临床资料，总结PLD的病因、发病机制、临床特征，查阅国内外有关PLD的文献并加以整理分析。结果 患者为38岁女性，既往多次多胎妊娠史。磁共振成像（MRI）检查确诊为Schnelldorfer D型PLD合并PKD。目前认为囊肿形成原因是先天性胆管上皮过度扩增和分泌过多液体，女性、雌激素、多胎妊娠是该病进展的危险因素；计算机断层扫描（CT）和MRI影像学检查是PLD诊断和分型的主要手段；治疗方式有手术和药物治疗。患者诊断明确，因经济原因未住院继续治疗，予以保肝、对症处理。结论 PLD发病机制尚不明确，一般进展缓慢，大多数PLD患者早期无明显症状。女性、多次多胎妊娠及雌激素作用可能是其发生进展的重要危险因素。腹部彩超是首选检查方法，增强CT和增强MRI是进一步明确分型及鉴别诊断的检查方法。目前尚无相关权威指南或统一标准指导临床实践。笔者基于病例特征和文献报道总结的PLD诊疗流程可供临床医生日常工作参考，但其规范合理性有待进一步商榷。

Abstract:背景与目的 脾动脉瘤（SAA）合并脐静脉开放在临床极为少见，肝硬化门静脉高压是导致SAA与脐静脉开放的原因之一。本文结合国内外文献报道，分析肝硬化门静脉高压引起SAA伴脐静脉开放的临床表现、影像学特点、诊断及治疗措施等，以期提高对该病的诊治水平。方法 回顾性分析1例肝硬化门静脉高压引起SAA并脐静脉开放患者的临床资料，并结合国内外文献，总结此病的临床和影像学特点、诊断及治疗方法。结果 患者为56岁女性，因突发意识障碍12 h入院。计算机断层扫描（CT）门静脉成像提示：所见门静脉主干及其主要分支增粗，宽度为28 mm，侧支循环开放，考虑门静脉高压；腹部CT平扫提示：肝硬化失代偿期，门静脉高压并侧支循环形成，伴脾大及少量腹水。行胃冠状静脉栓塞术+脐静脉栓塞术治疗。而后复查腹部增强CT检查提示：门静脉高压，并发SAA。经皮介入下SAA栓塞治疗，无不良并发症，术后顺利出院。结论 SAA合并脐静脉开放缺乏特异性临床表现，其诊断需综合患者临床表现、腹部CT血管造影及数字减影血管造影检查；一旦确诊，经皮介入微创治疗是有效手段。

Abstract:背景与目的 乳腺肿瘤是妇女常见疾病之一，准确判断乳腺肿瘤的良恶性是精准治疗的前提，本文旨在探讨双层探测器光谱CT多参数定量分析鉴别乳腺肿块良恶性的价值。方法 回顾性分析经病理证实，且行光谱CT双期增强扫描的25例乳腺肿块患者（31个病灶）资料，比较良、恶性组双期40 keV虚拟单能量图（VMI_{40 keV}）CT值及强化增值（?CT）、碘浓度（IC）及标准化碘浓度（NIC）、光谱曲线斜率（K）、有效原子序数（Z_eff）的差异。采用受试者工作特征（ROC）曲线分析比较各参数鉴别乳腺肿块良恶性的诊断效能。结果 乳腺恶性肿瘤动脉期VMI_{40 keV} ?CT及双期VMI_{40 keV} CT值、IC、NIC、K、Z_eff均大于良性肿瘤，差异均有统计学意义（均P<0.05）。动脉期各参数的曲线下面积（AUC）均高于静脉期，其中动脉期VMI_{40 keV} ?CT的AUC最大，AUC为0.899（95% CI=0.737~0.978），阈值为35.75 HU时，其鉴别乳腺肿块良恶性的敏感度、特异度、阳性预测值、阴性预测值分别为100.0%、81.8%、75.0%、100.0%。结论 双层探测器光谱CT多参数定量分析可有效鉴别乳腺肿块的良恶性，动脉期诊断效能高于静脉期，其中VMI_{40 keV} ?CT的诊断能力最佳。