Luteolin (LUT) belongs to a kind of flavonoid, which has protective effects on myocardial ischemia/reperfusion (I/R) injury. Sirt3 is located in mitochondria and interacts with Foxo3a to protect mitochondrial function against stress. Mitophagy is an important form of mitochondrial quality control. However, whether LUT regulates mitophagy to alleviate myocardial I/R injury via the Sirt3/Foxo3a pathway is rarely reported. In this study, 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP) is used to inhibit the Sirt3/Foxo3a pathway. Male adult rats are divided into four groups: Sham group, I/R group, I/R+LUT group, and I/R+LUT+3-TYP group. The I/R rats model is established by ligating the left anterior descending coronary artery for 30 min, then releasing the ligature for 24 h. Indexes of left ventricular function, myocardial damage, oxidative stress, and mitophagy are detected. It is found that LUT treatment activated Sirt3/Foxo3a pathway, improves left ventricular function, decreases myocardial infarction size, inhibits myocardial apoptosis and oxidative stress, and initiates mitophagy in I/R rats. Moreover, these protective effects of LUT are weakened when Sirt3 is inhibited. Together, LUT regulates mitophagy to alleviate myocardial I/R injury via the Sirt3/Foxo3a pathway.

BACKGROUND:Immunotherapy has emerged as a promising neoadjuvant strategy for hepatocellular carcinoma (HCC), with growing evidence supporting its role in tumor downstaging and enabling radical resection. Liver transplantation remains a curative option for HCC, and the integration of neoadjuvant immunotherapy prior to transplantation holds potential to improve staging outcomes and reduce postoperative recurrence. However, this approach necessitates careful evaluation of transplant-related immunological risks, particularly the risk of allograft rejection. RECENT FINDINGS:Recent clinical trials have provided key data on the efficacy and safety of pre-transplant immunotherapy. These studies highlight the importance of patient selection and risk management strategies to optimize treatment outcomes. Novel immunotherapeutic approaches are being explored, with a focus on identifying patients most likely to benefit from neoadjuvant therapy prior to liver transplantation. CONCLUSION:This review synthesizes emerging trends in the use of neoadjuvant immunotherapy for HCC patients undergoing liver transplantation. While immunotherapy shows promise in enhancing staging success and reducing recurrence, careful consideration of immunological risks and patient-specific factors is essential. Future research should continue to evaluate the long-term benefits and safety of this approach, as well as refine strategies for patient selection and risk mitigation. The integration of immunotherapy into pre-transplant care may represent a transformative advancement in the treatment of HCC, provided these challenges are addressed.

Oridonin, a bioactive diterpenoid derived from Rabdosia rubescens, has emerged as a promising anti-tumor agent with multifaceted roles in promoting tumor cell death and immune modulation. Recent evidence developments highlight its dual capacity to activate ferroptosis, a form of regulated, iron-dependent cell death, and the cGASSTING pathway. As a fundamental component of host defense, this critical DNA-sensing axis stimulates innate immunity. This review explores the mechanistic interconnection between these two processes, focusing on how Oridonin-induced oxidative stress and DNA damage drive immunogenic ferroptosis and lead to cytosolic DNA accumulation, which in turn triggers STING-mediated interferon responses. Such dual activation remodels the tumor immune microenvironment, enhances dendritic cell activation, and facilitates T cell-mediated tumor clearance. We further discuss the therapeutic potential of Oridonin in combination with ferroptosis inducers, immune checkpoint inhibitors, and STING agonists. Simultaneously, the use of carriers such as liposomes, micelles, and polymer nanoparticles can significantly improve the water solubility of Oridonin, prolong the circulation half-life, and achieve tumor-targeted enrichment through the enhanced permeability and retention (EPR) effect. Nanocarriers offer the ability to co-deliver Oridonin along with synergistic drugs, such as STING agonists and ferroptosis inducers, to ensure synchronized spatiotemporal release and enhance anti-tumor response. Nanocarriers are combined with imaging agents or biomarkers to achieve real-time monitoring of therapeutic response and dose optimization. However, we need to verify the long-term stability, safety, dose effectiveness, and individualized application potential of nanoformulations through large-scale clinical analyses. Nanotechnology has significantly improved the efficacy and safety of Oridonin through multi-dimensional strategies, providing crucial technical support for its clinical application in immunotherapy of solid tumors. A deeper understanding of these synergistic mechanisms provides essential insights into the development of nextgeneration cancer immunotherapies that leverage Oridonin's unique pharmacological characteristics.

Gastrointestinal (GI) malignancies, including gastric, colorectal, pancreatic, esophageal, and hepatocellular carcinomas, pose a substantial global health risk due to their high morbidity and death rates. Traditional interventions, including surgery, chemotherapy, and radiation therapy, have limited efficacy and frequently lead to adverse effects, thereby highlighting the need for novel therapeutic approaches. Chitosan, a biocompatible and biodegradable polysaccharide derived from chitin, has emerged as a promising agent in cancer therapy due to its unique properties, including mucoadhesion and pH responsiveness. Chitosan-based nanoparticles (NPs) designed for targeted drug delivery to cancer cells can facilitate prolonged drug release, overcome multidrug resistance, enhance therapeutic efficacy, and minimize systemic toxicity. Chitosan compounds have been shown to inhibit the growth and metastasis of gastric tumors while augmenting immune responses. Furthermore, chitosan-based nanocarriers can enhance the bioavailability of chemotherapeutic drugs and promote apoptosis in colorectal cancer cells, and have been used to boost targeted drug delivery and improve diagnostic sensitivity in pancreatic and esophageal malignancies. Likewise, chitosan-based systems have demonstrated therapeutic potential in hepatocellular carcinoma by enhancing drug accumulation in tumor tissues and promoting apoptosis. In this review, we have summarized the latest research on the application of chitosan and its derivatives in the treatment of gastrointestinal malignancies, with particular emphasis on the different delivery platforms like NPs, micelles, and hydrogels. In addition, the potential for developing advanced chitosan-based theragnostic systems for personalized therapy has also been highlighted.

Cancer continues to be a predominant cause of death globally, with tumor recurrence, metastasis, and medication resistance presenting substantial obstacles to traditional treatments, such as surgery, chemotherapy, and radiation. Phototherapy, which includes photothermal therapy (PTT) and photodynamic treatment (PDT), has emerged as a viable option owing to its noninvasive characteristics, low systemic toxicity, and remote controllability. Nonetheless, the effectiveness of these treatments is frequently constrained by suboptimal tumor cell uptake, hypoxia, and insufficient photosensitizer delivery. Recent breakthroughs in nanotechnology have resulted in the creation of carbohydrate polymer-based nanoparticles that optimize the distribution and targeting of photosensitizers, thereby enhancing the therapeutic efficacy of photothermal therapy (PTT) and photodynamic therapy (PDT). This study examined the incorporation of carbohydrate polymers, including chitosan, hyaluronic acid, gelatin, gum, agarose, and starch, with phototherapy for oncological treatment. These polymers, which are known for their biocompatibility, biodegradability, and modifiability, were integrated with inorganic nanoparticles to produce hybrid materials with improved photothermal and photodynamic properties. This paper delineates several ways, such as employing chitosan-gold nanorods for integrated gene therapy and photothermal treatment, utilizing hyaluronic acid-based nanoparticles for targeted drug delivery, and implementing gelatin-stabilized gold nanorods to enhance photothermal efficiency. The discussion includes a combination of phototherapy with chemotherapy, gene therapy, and immunotherapy, highlighting the potential synergistic benefits in cancer treatment. This study closes with prospective advancements in the creation of multifunctional nanoplatforms aimed at enhancing the efficacy and personalization of cancer treatments.

Alcohol-associated liver disease (ALD) remains a predominant cause of chronic hepatic pathology, and effective therapeutic strategies are needed. Krüppel-like factor 15 (KLF15) is a member of the KLF family of zinc-finger transcription factors and is ubiquitously expressed in metabolically active tissues, with a particularly high abundance in the liver. KLF15 has been implicated in various hepatic disorders. In this study, we investigated the pathophysiological role of KLF15 in ALD. We established a National Institute on Alcohol Abuse and Alcoholism (NIAAA) model in mice by feeding them an ethanol Lieber–DeCarli liquid diet containing 5

Hypoxic microenvironment is a hallmark feature of hepatocellular carcinoma (HCC) and contributes to cancer progression. RHPN1-AS1, a long noncoding RNA (lncRNA), plays an important role in multiple cancers. However, its expression and oncogenic function under hypoxic conditions have not yet been determined. In this study, we investigated the expression changes of RHPN1-AS1 in HCC cells upon hypoxia. The effects of RHPN1-AS1 knockdown and overexpression on hypoxic HCC cells were explored. The protein partner involved in RHPN1-AS1 action in hypoxic HCC cells was characterized. We found that exposure to hypoxia led to an increase in the RHPN1-AS1 level in HCC cells, which was blocked by depletion of HIF-1α. Chromatin immunoprecipitation assay revealed the enrichment of HIF-1α at the promoter of RHPN1-AS1 in hypoxic HCC cells. Knockdown of RHPN1-AS1 suppressed HCC cell proliferation, colony formation, and invasion under hypoxia, whereas overexpression of RHPN1-AS1 promoted the proliferation and invasion of hypoxic HCC cells. Mechanistically, RHPN1-AS1 interacted with and stabilized RPS15A protein in hypoxic HCC cells. Elevated expression of RPS15A protein enhanced the proliferation and invasion of hypoxic HCC cells through activation of β-catenin signaling. Silencing of RPS15A attenuated RHPN1-AS1-induced aggressiveness and β-catenin activation in hypoxic HCC cells. In vivo tumorigenic studies confirmed that RPS15A depletion significantly reduced the growth of RHPN1-AS1-overexpressing HCC xenograft tumors. RHPN1-AS1 serves as a hypoxia-responsive lncRNA and interacts with the RPS15A protein partner to activate the β-catenin pathway, consequently enhancing HCC progression under hypoxia.

Background: The in-depth understanding of the fine anatomy of the liver has promoted the development of modern liver surgery. With the rapid popularity of laparoscopic hepatectomy, the membrane structure of the liver and its ability to dissect the intrahepatic and extrahepatic vascular system more conveniently and accurately has been gradually emphasized. Objective: Exploring the value of extrahepatic sheath dissection of the hepatic pedicle in minimally invasive anatomical hepatectomy with cystic plate approach. This study aims to assess the benefits of integrating the cystic plate approach with real-time guided laparoscopic anatomical hepatectomy, in comparison with conventional laparoscopic anatomical hepatectomy. Materials and methods: Based on the theory of cystic plate and hepatic portal plate, the authors have pioneered the fluorescence real-time guided cystic plate approach in hepatectomy. The article focuses on the anatomical knowledge and technical difficulties of anatomical hepatectomy with fluoroscopic laparoscopic cystic plate approach and explores the safety and practicality of the cystic plate approach in laparoscopic anatomical hepatectomy. Additionally, a retrospective cohort study was also conducted to compare the operation time, intraoperative blood loss, and postoperative complications between the cystic plate approach and the conventional approach during fluoroscopic laparoscopic hepatectomy. Results: A total of 38 patients who met the inclusion criteria underwent laparoscopic hepatectomy between January 2019 and November 2022. No significant disadvantages were found in terms of operation time and intraoperative blood loss during the surgeries. Furthermore, the postoperative indications, including liver function indexes on the first postoperative day, WBC, and the postoperative hospital stay, were also not affected, thus proving the safety of the cystic approach. Importantly, through the cystic plate approach, the target liver pedicle was fully freed, and then the segments to be resected were precisely marked by positive or negative staining, followed by hepatectomy under real-time fluoroscopic guidance. This approach is extremely advantageous in anatomical liver segment resections, especially in right posterior lobe or hemi-hepatectomy, without increasing intraoperative bleeding or postoperative complication rates. Conclusion: This technique allows for easy and safe freeing of the target liver pedicle using membrane structures, and also allows for precise anatomical hepatectomy in combination with real-time fluoroscopic laparoscopic navigation.

Liver diseases, characterized by metabolic disorder, have become a global public health problem with high morbidity and mortality. Krüppel-like factor 15 (KLF15) is a zinc-finger transcription factor mainly enriched in liver. Increasing evidence suggests that hepatic KLF15 is activated rapidly during fasting, and contributes to the regulation of gluconeogenesis, lipid, amino acid catabolism, bile acids, endobiotic and xenobiotic metabolism. This review summarizes the latest advances of KLF15 in metabolic reprogramming, and explore the function of KLF15 in acute liver injury, hepatitis B virus, and autoimmune hepatitis. which aims to evaluate the potential of KLF15 as a therapeutic target and prognostic biomarker for liver diseases.

Homologous repair deficiency (HRD) impedes double-strand break repair, which is a common driver of carcinogenesis. Positive HRD status can be used as theranostic markers of response to platinum- and PARP inhibitor-based chemotherapies. Here, we aimed to fully investigate the therapeutic and prognostic potential of HRD in pancreatic adenocarcinoma (PAAD) and identify effective biomarkers related to HRD using comprehensive bioinformatics analysis. The HRD score was defined as the unweighted sum of the LOH, TAI, and LST scores, and it was obtained based on the previous literature. To characterize PAAD immune infiltration subtypes, the "ConsensusClusterPlus" package in R was used to conduct unsupervised clustering. A WGCNA was conducted to elucidate the gene coexpression modules and hub genes in the HRD-related gene module of PAAD. The functional enrichment study was performed using Metascape. LASSO analysis was performed using the "glmnet" package in R, while the random forest algorithm was realized using the "randomForest" package in R. The prognostic variables were evaluated using univariate Cox analysis. The prognostic risk model was built using the LASSO approach. ROC curve and KM survival analyses were performed to assess the prognostic potential of the risk model. The half-maximal inhibitory concentration (IC50) of the PARP inhibitors was estimated using the "pRRophetic" package in R and the Genomics of Drug Sensitivity in Cancer database. The "rms" package in R was used to create the nomogram. A high HRD score indicated a poor prognosis and an advanced clinical process in PAAD patients. PAAD tumors with high HRD levels revealed significant T helper lymphocyte depletion, upregulated levels of cancer stem cells, and increased sensitivity to rucaparib, Olaparib, and veliparib. Using WGCNA, 11 coexpression modules were obtained. The red module and 122 hub genes were identified as the most correlated with HRD in PAAD. Functional enrichment analysis revealed that the 122 hub genes were mainly concentrated in cell cycle pathways. One novel HRD-related gene signature consisting of CKS1B, HJURP, and TPX2 were screened via LASSO analysis and a random forest algorithm, and they were validated using independent validation sets. No direct association between HRD and CKS1B, HJURP, or TPX2 has not been reported in the literature so far. Thus, these findings indicated that CKS1B, HJURP, and TPX2 have potential as diagnostic and prognostic biomarkers for PAAD. We constructed a novel HRD-related prognostic model that provides new insights into PAAD prognosis and immunotherapy. Based on bioinformatics analysis, we comprehensively explored the therapeutic and prognostic potential of HRD in PAAD. One novel HRD-related gene signature consisting of CKS1B, HJURP, and TPX2 were identified through the combination of WGCNA, LASSO analysis and a random forest algorithm. A novel HRD-related risk model that can predict clinical prognosis and immunotherapeutic response in PAAD patients was constructed.

To evaluate the effectiveness and safety of transarterial chemoembolization (TACE) combined with immune and targeted therapy in unresectable hepatocellular carcinoma (HCC). Prospective analysis of 23 patients with intermediate or advanced primary HCC treated at the Department of Hepatic Surgery, The First Affiliated Hospital of the University of Science and Technology of China from July 2019, including 11 cases treated with TACE alone and 12 cases treated with TACE combined with targeted therapy. The basal indexes of patients in the two groups were compared, and the response during treatment was observed; regular follow-up was performed to assess the efficacy of tumor treatment. Compared with TACE treatment alone, the objective response rate (ORR) was significantly higher in the TACE combined with targeted treatment group (50.0

Chronic glomerulonephritis (CGN) is one of the leading causes of end-stage renal disease (ESRD). A growing body of literature emphasizes the important role of long non-coding RNAs (lncRNAs) in the development and progression of the disease. However, the function of NONRATG001910.2 in the development of CGN was not well understood. This research aimed to investigate the effect of NONRATG001910.2 on CGN and revealed its potential molecular mechanisms. In this work, the expression of NONRATG001910.2 was detected by quantitative real-time polymerase chain reaction (qRT-RCR) in cell lines. We found that NONRATG001910.2 was significantly up-regulated in lipopolysaccharide (LPS) induced cells. High NONRATG001910.2 levels were associated with the development of CGN. In addition, NONRATG001910.2 knockdown inhibited cell proliferation and cell cycle. At the same time, we found that up-regulation of microRNA-339-3p (miR-339-3p) abrogated the biological roles of NONRATG001910.2 up-regulation. Moreover, the knockdown of CTNNB1 can upregulate miR-339-3p expression, thereby inhibiting cell proliferation. In conclusion, these results demonstrated that NONRATG001910.2 in LPS-stimulated rat mesangial cell line HBZY-1 (HBZY-1) by targeting miR-339-3p, which subsequently promotes the expression of CTNNB1, and suggested that NONRATG001910.2 may be a potential biomarker.

With the development of genomics, the update of modern imaging technology and the advent of artificial intelligence and big data, the surgical treatment of gastric cancer has gradually stepped into precision medicine. Precision surgery treatment of gastric cancer is based on accurate molecular typing and staging using modern molecular diagnostic technology and imaging, and the formulation of precise and individualized surgical treatment plans, with the concept of minimally invasive and accelerated rehabilitation surgery running through it. For intermediate-stage gastric cancer, we have adopted a comprehensive treatment approach including traditional radiotherapy and chemotherapy, targeted therapy and immunotherapy. Utilize artificial intelligence and big data technology to improve the standardization and interconnectivity of specialty data and realize the transformation of evidence-based medicine. Promoting the standardization, standardization and individualization of gastric cancer surgical treatment, providing patients with precise diagnosis and treatment, and further improving patients? prognosis are the opportunities and challenges in the development of gastric cancer surgery.

The global incidence of liver cancer continues to grow. Liver cancer, especially hepatocellular carcinoma, has high recurrence and mortality rates. Here, we review the past decade's diagnostic, therapeutic, and management strategies for hepatocellular carcinoma, and summarize new patient management approaches, including enhanced recovery after surgery, targeted therapy, and immunotherapy. We compare traditional and innovative management methods, which comprise developments in precision medicine, and consider their limitations. Ongoing innovation and technological advances enable surgeons to gain deeper understandings of the multidimensionality of hepatocellular carcinoma, thereby promoting the continuous development of precision therapy.

In the past 20 years, the concept of surgery has undergone profound changes. Surgical practice has shifted from emphasizing the complete elimination of lesions to achieving optimal rehabilitation in patients. Collaborative optimization of surgery consists of three core elements, removal of lesions, organ protection and injury close monitoring, and controlled surgical intervention. As a result, the traditional surgical paradigm has quietly transformed into a modern precision surgical paradigm. In this review, we summarized the latest breakthroughs and applications of precision medicine in liver surgery. In addition, we also outlined the progresses that have been made in precision liver surgery, the opportunities and challenges that may encountered in the future.

Acute myeloid leukaemia (AML) remains a therapeutic challenge and improvements in chemotherapy are needed. 4‐Amino‐2‐trifluoromethyl‐phenyl retinate (ATPR), a novel all‐trans retinoic acid (ATRA) derivative designed and synthesized by our team, has been proven to show superior anticancer effect compared with ATRA on various cancers. However, its potential effect on AML remains largely unknown. Lactate dehydrogenase B (LDHB) is the key glycolytic enzyme that catalyses the interconversion between pyruvate and lactate. Currently, little is known about the role of LDHB in AML. In this study, we found that ATPR showed antileukaemic effects with RARα dependent in AML cells. LDHB was aberrantly overexpressed in human AML peripheral blood mononuclear cell (PBMC) and AML cell lines. A lentiviral vector expressing LDHB‐targeting shRNA was constructed to generate a stable AML cells with low expression of LDHB. The effect of LDHB knockdown on differentiation and cycle arrest of AML cells was assessed in vitro and vivo, including involvement of Raf/MEK/ERK signalling. Finally, these data suggested that ATPR showed antileukaemic effects by RARα/LDHB/ ERK‐glycolysis signalling axis. Further studies should focus on the underlying leukaemia‐promoting mechanisms and investigate LDHB as a therapeutic target.

2019 novel coronavirus pneumonia is a serious life-threatening disease and it has affected many people globally, especially the people who live in China. A high prevalence of hepatobiliary diseases has been observed in 2019-nCoV patients and some may require emergency surgery. In the context of the novel coronavirus pneumonia, new challenges have arisen for surgeons in terms of ways to effectively treat outpatients, safety of medical staffs in performing surgery treatment, and the lack of efficient postoperative management and follow-up procedure. It is hoped that through this article, surgeons will have a better system in hepatobiliary diseases classification, treatment selection, and protective measures to improve the clinical practice in accordance with the guidelines for the diagnosis and treatment of the novel coronavirus pneumonia.

To evaluate the clinical significance of fusion indocyanine green (ICG) fluorescence imaging in precise right hemihepatectomy for the treatment of hepatocellular carcinoma (HCC). 47 patients with HCC who underwent right hemihepatectomy were retrospectively analyzed. 18 of them guided by fusion ICG fluorescence imaging (FIGFI) while 29 patients underwent conventional right hepatectomy without guidance. Compared to the patients with conventional treatment, the intraoperative blood loss of the patients with guided surgery was significantly less, and no transfusion and hepatic occlusion were performed during the operation. Liver function recovery faster in guided group. The incidence of postoperative complications is also lower, and the recurrence rate in one year is significantly reduced. ICG fluorescence range of 18 patients in liver surface was consistent with the ischemic line, and their postoperative liver cross-sections were clearly demarcation. There were no significant differences in the mean operation time, blood loss, postoperative hospital stays, cases of blood transfusion, complication rate, or postoperative peak volume of ALT and TB between positive or negative staining groups. Pathology results of all patients demonstrated HCC and negative margins, and microvascular invasion occurred in 8 cases. The average follow-up time of 18 patients was 16.7 months, and recurrence was found in 5 cases after surgery. FIGFI could guide the anatomical right hepatectomy with real -time increased radical rate, accuracy and safety for the treatment of HCC, and therefore showed a promising prospect.

Ferroptosis, a newly discovered form of non-apoptotic cell death, is induced by an excessive degree of iron-dependent lipid peroxide. ATPR, a novel all-trans retinoic acid (ATRA) derivative, has been extensively developed to show superior anticancer effect than ATRA in acute myeloid leukemia (AML). However, whether ferroptosis exists during ATPR treatment of AML remains unclear. Herein, we found that ferroptosis occurred in an AML xenograft mouse model of ATPR treatment. In vitro, ATPR was verified to induce ferroptosis in a dose-dependent manner by proferroptotic protein marker, lipid peroxidation, and lipid ROS, which could be significantly reversed by ferrostatin-1. Using lysosomal inhibitor chloroquine and iron chelator desferrioxamine, we further revealed that ATPR-induced ferroptosis was regulated by autophagy via iron homeostasis, especially Nrf2. Furthermore, targeting ferroptosis contributes to ATPR-induced AML differentiation. In conclusion, these results indicated that ferroptosis play an important role in ATPR-induced differentiation, and suggested that ATPR would provide a potential therapeutic value for AML treatment.

原发性肝癌作为全球第4位肿瘤相关致死性疾病,一直被列为重要的公共健康问题.世界卫生组织保守估计,至2030年将有100万病人死于原发性肝癌[1].其中肝细胞肝癌(hepatocellular carci-noma, HCC)占原发性肝癌的90％.无论对于早期HCC还是迸展期HCC,尽管目前存在大量治疗方式,但手术根治切除仍是最有效的[2].