TATA-binding protein-associated factor 3 (TAF3), a member of the TAF family, plays a crucial role in safeguarding finely balanced transcriptional programs. Previous research identified TAF3 as a critical prognostic marker in hepatocellular carcinoma (HCC). This study aimed to elucidate TAF3’s functional role and mechanistic underpinnings in liver cancer progression. Through the establishment of stable TAF3-knockdown and overexpression cell lines in human HCC cells (HepG2 and MHCC97H), comprehensive functional analyses revealed that TAF3 knockdown significantly inhibited cancer cell proliferation, migration, and invasion, while its overexpression promoted these malignant phenotypes. Clinically, elevated TAF3 expression correlated with aggressive clinicopathological features and poor prognosis in HCC patients. Mechanistic investigations demonstrated that TAF3 transcriptionally activates sterol regulatory element-binding protein 2 (SREBP2), a master regulator of cholesterol synthesis, leading to increased intracellular cholesterol accumulation. This cholesterol elevation functionally contributed to oncogenic processes, as exogenous cholesterol supplementation reversed the impaired malignancy in TAF3-deficient cells. In vivo validation using a subcutaneous xenograft mouse model confirmed that TAF3 knockdown suppressed tumor growth, an effect effectively counteracted by high-cholesterol dietary intervention. Collectively, these findings establish that TAF3 promotes liver cancer progression through transcriptional activation of SREBP2 and subsequent enhancement of cholesterol biosynthesis. The study identifies a novel TAF3/SREBP2/cholesterol axis as a promising therapeutic target in TAF3-overexpressing hepatocellular carcinomas, providing mechanistic insights into the interplay between transcriptional regulation and metabolic reprogramming in cancer progression.

Organ transplantation is the definitive treatment for end-stage organ failure, yet long-term graft survival remains substantially limited by ischemia-reperfusion injury (IRI), allograft rejection, and chronic graft dysfunction. Current immunosuppressive regimens have not fully exploited the metabolic plasticity of macrophages, which are central orchestrators of both innate and adaptive immune responses in transplanted organs. Macrophages display remarkable functional plasticity, classically defined by pro-inflammatory (M1)/anti-inflammatory (M2) polarization, and this dual capacity renders them uniquely impactful in transplanted organs. Accumulating immunometabolic evidence indicates that this plasticity is governed by dynamic metabolic reprogramming orchestrated by key metabolic nodes: M1 macrophages rely primarily on aerobic glycolysis and secrete proinflammatory cytokines, such as IL-1β, IL-6, and TNF-α, whereas M2 macrophages depend on oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) to sustain anti-inflammatory and tissue-repair programs. For example, pyruvate kinase M2, a key glycolytic enzyme, promotes M1 polarization via glycolytic reprogramming and HIF-1α-dependent inflammatory gene transcription, whereas the carnitine palmitoyltransferase 1A, a rate-limiting enzyme in FAO, supports M2 polarization through FAO-driven OXPHOS. Core metabolic pathways encompass carbohydrate metabolism-glycolysis, the tricarboxylic acid cycle, and the pentose phosphate pathway-alongside FAO and amino acid catabolism. These pathways are dynamically modulated by microenvironmental cues, such as hypoxia, lactate, and succinate, and in turn dictate macrophage phenotypic identity and effector function. In this review, we comprehensively review the molecular mechanisms underpinning macrophage metabolic reprogramming, from early IRI and acute rejection to chronic rejection, fibrosis, and post-transplant tumor recurrence, linking metabolism to alloimmunity and oncological risk. Emerging therapeutic strategies target macrophage metabolism, including metabolic enzyme inhibitors such as 2-deoxyglucose, which attenuates chronic lung allograft dysfunction, cell-based therapies, nanoparticles, and gene editing, for example macrophage-specific MEK1/2 ablation via CRISPR/Cas9, which reprograms glycolysis to OXPHOS and ameliorates cardiac rejection. Harnessing these metabolic nodes may complement current immunosuppression and improve graft survival, warranting future clinical evaluation.

BackgroundLong-term immunosuppression following transplantation places recipients at a high risk of malignancy. Hepatocellular carcinoma (HCC) recurrence after transplantation poses significant challenges to long-term survival of recipients. Several studies in transplant oncology have established cancer-transplant models to support the development of therapies for reducing the risk of post-transplant cancer recurrence. However, existing models fail to recapitulate the complex immune status of recipients and the authentic tumor microenvironment after transplantation.MethodsC57BL/6 recipient mice were injected intravenously with luciferase-expressing Hepa1-6 cells 7 days before receiving Balb/c cardiac allografts, followed by post-transplant immunosuppression with tacrolimus. On day 7 post-transplantation, the immune state of recipients was assessed by measuring serum inflammatory cytokines, and allograft rejection was evaluated by hematoxylin-eosin staining. Cancer progression was evaluated using in vivo imaging and measurements of serum alpha-fetoprotein levels, with subsequent histological confirmation.ResultsAllogeneic cardiac transplantation resulted in a significant increase in serum levels of pro-inflammatory cytokines accompanied by a marked reduction in cancer burden. Marked lymphocytic infiltration, hemorrhage, and structural disintegration were observed in the grafts of untreated animals. In contrast, tacrolimus treatment effectively attenuated both the inflammatory cytokine response and acute allograft rejection but, conversely, resulted in a significant increase in tumor burden. Histological analysis confirmed that malignancies were exclusively localized to the lungs, mirroring the most common site of clinical HCC recurrence post-transplantation.ConclusionThis model effectively simulates the elevated risk of cancer recurrence under post-transplant immunosuppression and faithfully recapitulates lung metastasis of HCC mediated by circulating cancer cells—the most common site of clinical recurrence following liver transplantation for HCC. It thus provides a reliable tool for basic research aimed at reducing risk of post-transplant cancer recurrence.

BACKGROUND The early detection of hepatocellular carcinoma (HCC) remains a major clinical challenge due to the limited sensitivity and specificity of current biomarkers. This study sought to develop a diagnostic model based on serum exosomal microRNAs (miRNAs) and to elucidate the functional mechanism of a key miRNA, miR-200b-3p, in HCC pathogenesis. AIM To develop and validate a serum exosomal miRNA-based diagnostic model for HCC. METHODS Serum exosomes were isolated from a discovery cohort (68 HCC, 131 non-HCC) and a validation cohort (66 HCC, 135 non-HCC). Candidate miRNAs were identified via next-generation sequencing and machine learning, and validated by quantitative real-time polymerase chain reaction. A diagnostic model was constructed using logistic regression. The role of miR-200b-3p was examined using in vitro functional assays. RESULTS A diagnostic model incorporating three exosomal miRNAs (miR-200b-3p, miR-215-5p, miR-452-5p) and age was established. It showed strong performance in the training set (area under the curve = 0.863, sensitivity = 86.4%, specificity = 76.5%; all P < 0.001). Mechanistically, miR-200b-3p acted as a tumor suppressor by directly targeting phosphoserine aminotransferase 1. Its overexpression inhibited HCC cell proliferation, migration, and invasion (all P < 0.05), while knockdown promoted these phenotypes (all P < 0.05). CONCLUSION This study establishes and validates a non-invasive exosomal miRNA-based diagnostic model for HCC, reveals that miR-200b-3p directly targets phosphoserine aminotransferase 1, and provides mechanistic support for early detection.

BACKGROUND:Accurate quantification of microRNAs (miRNAs) is essential for early cancer detection, yet remains challenging due to their short length, low abundance, and high sequence similarity. Existing assays often struggle to achieve sufficient sensitivity, specificity, and robustness for reliable clinical deployment. RESULTS:We introduce SPARC, a programmable molecular diagnostic platform that integrates a signal-triggered primer exchange reaction, self-supplied crRNA generation, and a tiered PER-transcription-CRISPR/Cas12a amplification cascade. Using miRNA-21 as a model, SPARC achieves an ultralow detection limit of 1.22 fM and a broad quantitative range from 1 fM to 100 nM. The system exhibits high specificity, strong analytical stability, and modular adaptability to diverse targets, including miRNA-122. Notably, the dual-directional profiling of oncogenic and tumor-suppressive miRNAs enhances diagnostic resolution. When applied to HCC cell lines and clinical tissues, SPARC accurately distinguished malignant from normal samples and showed excellent agreement with qRT-PCR measurements and histopathological assessments. SIGNIFICANCE:This streamlined and self-amplifying cascade system provides a scalable, robust, and clinically compatible platform for ultrasensitive miRNA detection. SPARC holds strong potential for early hepatocellular carcinoma screening, molecular subtyping, and broader precision oncology applications.

Hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) remains a major cause of mortality, with current selection criteria such as the Milan and UCSF standards relying solely on tumor morphology and failing to fully account for biological aggressiveness. Emerging evidence implicates dysregulated lipid metabolism, particularly sterol regulatory element-binding protein 2 (SREBP2), in HCC progression, yet its prognostic role in post-LT recurrence remains unexplored. To address this gap, this study developed and validated a novel SREBP2-integrated nomogram for improved risk stratification in 206 HCC patients undergoing LT (2015-2022), randomly split into development (n = 144) and validation (n = 62) cohorts. SREBP2 levels were quantified via ELISA (sensitivity: 0.1 ng/mL) and then incorporated into a multivariate Cox model alongside tumor number and AFP to predict recurrence-free survival (RFS). The nomogram demonstrated superior discrimination, with C-indices of 0.778 (development) and 0.796 (validation). High SREBP2 levels (≥ 40 ng/mL) independently predicted recurrence (HR = 1.757, p = 0.011), whereas decision curve analysis confirmed greater clinical net benefit across 1-/3-/5-year RFS predictions. As the first study to integrate SREBP2 into LT candidate selection, this biologically informed nomogram significantly enhances recurrence prediction, offering a refined tool for transplant eligibility assessment and adjuvant therapy guidance in HCC management. By combining molecular biomarkers with clinical parameters, this approach addresses a critical unmet need in optimizing post-LT outcomes.

BackgroundLong-term immunosuppression following organ transplantation results in an elevated risk of malignancies in recipients, which constitutes a major factor limiting their long-term survival. Therefore, the development of immunosuppressant with anti-tumor efficacy holds critical significance. Icaritin (ICT), a clinically employed antitumor drug, enhances anti tumor immunity by reshaping the tumor immune microenvironment. Moreover, recent evidence highlights its immunomodulatory role in mitigating multiple autoimmune diseases. However, whether ICT can attenuate the allograft rejection remains poorly characterized.MethodsFully major histocompatibility complex-mismatched heterotopic heart transplantation was conducted from BALB/c mice to C57BL/6J mice. The rejection of the allografts was assessed via H&E staining and immunohistochemistry. Single-cell RNA sequencing (scRNA-seq) and flow cytometry were carried out on recipient splenocytes. In vitro, isolated naïve CD4+ T cells were cultured in Th1-polarizing conditioned medium with various treatments, and flow cytometry and quantitative PCR (qPCR) were employed to delineate the role of the Proviral integration site for Moloney murine leukemia virus (PIM1) during Th1 cell differentiation. Molecular docking, molecular dynamics simulations, and cellular thermal shift assay were employed to demonstrate the binding capacity between ICT and CCAAT/enhancer-binding protein β (CEBPB). A tumor-bearing murine heterotopic heart transplantation model was employed to demonstrate the dual efficacy of ICT in immunosuppression and antitumor.ResultsICT markedly attenuated acute cardiac allograft rejection and enhanced graft survival. scRNA-seq and flow cytometric analyses revealed a significant reduction in the proportion of splenic Th1 cells in ICT-treated recipient mice. In vitro, ICT suppressed CD4+ T-cell activation, proliferation, and Th1 cell differentiation in a dose-dependent manner. By binding to the transcription factor CEBPB, ICT inhibits PIM1 expression, and thereby suppresses the activation, proliferation, and Th1 differentiation of CD4+ T cells. In the tumor-bearing murine heart transplantation model, ICT potentiated the immunosuppressive efficacy of tacrolimus while reducing the tumor burden.ConclusionsWhile exerting antitumor effects, ICT attenuates allograft rejection by targeting the CEBPB/PIM1 axis, thereby suppressing CD4+ T-cell activation, proliferation, and Th1 differentiation.

ABSTRACT Objective Capecitabine (CAP) is an orally administered prodrug of fluorouracil, predominantly utilized in the treatment of solid tumors. Triggering tumor ferroptosis is an important mechanism for the treatment of hepatocellular carcinoma (HCC). However, the potential of CAP to induce ferroptosis in HCC, along with the underlying mechanisms, remains unknown. Methods In this study, a subcutaneous HCC model was constructed using the syngeneic Hepa1‐6 cell line in C57BL/6 mice, followed by treatment with metronomic CAP (mCAP). The anti‐tumor effects of mCAP were evaluated by monitoring tumor volume, performing pathological staining, and evaluating tumor oxidative stress levels. In vitro, various thymidylate synthase (TYMS) inhibitors were used to treat both mouse and human HCC cell lines. Furthermore, TYMS‐overexpressing plasmids were transfected into mouse and human HCC cell lines to directly investigate their impact on intracellular oxidative stress. Intracellular oxidative stress and ferroptosis‐related markers were detected using flow cytometry, transmission electron microscopy, and Western blotting. Results 5‐FU, an active metabolite of CAP, as well as TYMS‐specific inhibitors, suppressed the proliferation of Hepa1‐6 and HepG2 cells. These treatments promoted p67phox expression, activated nicotinamide adenine dinucleotide phosphate hydrogen oxidase (NOX), induced reactive oxygen species production, and increased ferrous ion accumulation. Electron microscopy revealed mitochondrial alterations characteristic of ferroptosis. Raltitrexed, another TYMS inhibitor, also induced ferroptosis in hepatocellular carcinoma cells. In vivo, the anti‐tumor effect of mCAP was antagonized by co‐treatment with an NOX inhibitor. Conclusion CAP targets TYMS to induce ferroptosis by activating NOX, thereby inhibiting HCC progression.

Abstract Background Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) poses a considerable challenge for the long-term treatment of non-small cell lung cancer (NSCLC). This study aims to identify a novel biomarker associated with osimertinib resistance and explore its role in EGFR-TKI resistance in lung adenocarcinoma (LUAD). Methods Comprehensive bioinformatics analysis were done using transcriptomic data from the TCGA and GEO databases to identify genes associated with osimertinib tolerance. Candidate genes were further screened against a histone modification-related gene set from MSigDB, leading to the identification of TLE1. The hub gene, TLE1, was further evaluated through survival analysis, GSEA and CIBERSORT analyses. Loss-of-function experiments performed in vitro were utilized to assess the impact of TLE1 on osimertinib resistance in LUAD. Results TLE1 was of particularly noteworthy, exhibiting elevated expression in LUAD, especially in stage IV patients, and was associated with poor prognosis. GSEA results showed that mTOR, VEGF and HIF-1 signaling pathways were notably activated in the high TLE1 expression group. CIBERSORT analysis markedly elevated levels of regulatory T cells (Tregs) in the TLE1 high expression group. Additionally, epithelial-mesenchymal transition (EMT) scores were significantly elevated in osimertinib tolerant groups and exhibited a positive correlation with TLE1 expression. Furthermore, TLE1 expression was significantly higher in osimertinib-resistant PC9 cells compared to parental PC9 cells. Downregulation of TLE1 enhanced the sensitivity of osimertinib-resistant PC9 cells to osimertinib. Conclusions TLE1 was identified as a critical gene associated with osimertinib tolerance, influencing LUAD progression, potentially serving as a novel therapeutic target. Clinical trial number Not applicable.

Capecitabine (CAP) is widely used in cancer treatment for its oral convenience and tumor targeting. However, its effectiveness in hepatocellular carcinoma (HCC) is suboptimal, possibly due to metabolic enzyme expression differences. This study aims to analyze these enzymes’ expression differences and explore their correlation with clinical pathological factors, to inform personalized CAP treatment. This retrospective study used Immunohistochemistry (IHC) to analyze tumor and non-tumorous samples from HCC patients for CAP metabolic enzyme expression. PRM protein quantification was performed on 10

Extracellular vesicles (EVs) are heterogeneous vesicles released by donor cells that can be taken up by recipient cells, thus inducing cellular phenotype changes. Since their discovery decades ago, roles of EVs in modulating initiation, growth, survival and metastasis of cancer have been revealed. Recent studies from multifaceted perspectives have further detailed the contribution of EVs to cancer drug resistance; however, the role of EV uptake in conferring drug resistance seems to be overlooked. In this comprehensive review, we update the EV subtypes and approaches for determining EV uptake. The biological basis of EV uptake is systematically summarized. Moreover, we focus on the diverse uptake mechanisms by which EVs carry out the intracellular delivery of functional molecules and drug resistance signaling. Furthermore, we highlight how EV uptake confers drug resistance and identify potential strategies for targeting EV uptake to overcome drug resistance. Finally, we discuss the research gap on the role of EV uptake in promoting drug resistance. This updated knowledge provides a new avenue to overcome cancer drug resistance by targeting EV uptake.

BACKGROUND:Emergency abdominal surgery involves complex, diverse conditions with high patient variability, posing recovery challenges. While Enhanced Recovery After Surgery (ERAS) programs benefit elective surgery and show promise in emergencies, current research is disease-specific, limiting broad assessment. This study evaluates ERAS safety/effectiveness across multiple emergency abdominal conditions and identifies recovery risk factors. METHODS:This single-blind trial randomized 305 emergency abdominal surgery patients to ERAS (n = 151) or conventional care (n = 154). ERAS patients underwent perioperative enhanced recovery programs, while controls received conventional management. The primary outcome was time to postoperative recovery criteria. Secondary outcomes included first postoperative flatus/semi-liquid diet tolerance time, complication rates, maximum pain scores (days 1-5), 30-day readmissions, and satisfaction. Data were analyzed via t-tests, Mann-Whitney U, Fisher's exact tests, and multivariate regression (p < 0.05 significance). RESULTS:ERAS reduced median recovery time (141 h [IQR: 114-179] vs. 163 h [IQR: 131-204], p < 0.001), accelerated gastrointestinal recovery (first flatus: 1.10 vs. 1.30 days; semi-liquid tolerance: 3.60 vs. 4.10 days, both p < 0.05), and improved satisfaction (95 vs. 91, p < 0.001). No differences in complications (11.9% vs. 15.6%, p = 0.353) or 30-day readmissions (2.0% vs. 2.6%, p > 0.999). Shock index and APACHE II were common risk factors; ERAS-specific risks included SOFA (OR = 1.31, 1.03-1.71, p = 0.034), preoperative hemoglobin (OR = 0.95, 0.89-1.00, p = 0.046), preparation time (OR = 0.33, 0.14-0.68, p = 0.005), and blood transfusion (OR = 0.01, 0.00-0.23, p = 0.003). CONCLUSION:ERAS enhances postoperative recovery and satisfaction in emergency abdominal surgery without increasing complications/readmissions. Identified risk factors support personalized protocols, advancing ERAS implementation.

We report the 1-year results from one patient as the preliminary analysis of a first-in-human phase I clinical trial (ChiCTR2300072200) assessing the feasibility of autologous transplantation of chemically induced pluripotent stem-cell-derived islets (CiPSC islets) beneath the abdominal anterior rectus sheath for type 1 diabetes treatment. The patient achieved sustained insulin independence starting 75 days post-transplantation. The patient’s time-in-target glycemic range increased from a baseline value of 43.18% to 96.21% by month 4 post-transplantation, accompanied by a decrease in glycated hemoglobin, an indicator of long-term systemic glucose levels at a non-diabetic level. Thereafter, the patient presented a state of stable glycemic control, with time-in-target glycemic range at >98% and glycated hemoglobin at around 5%. At 1 year, the clinical data met all study endpoints with no indication of transplant-related abnormalities. Promising results from this patient suggest that further clinical studies assessing CiPSC-islet transplantation in type 1 diabetes are warranted.

Objectives Previous studies elucidated that capecitabine (CAP) works as an anti-tumor agent with putative immunosuppressive effects. However, the intricate mechanisms underpinning these effects remain to be elucidated. In this study, we aimed to unravel the molecular pathways by which CAP exerts its immunosuppressive effects to reduce allograft rejection. Methods Hearts were transplanted from male BALB/c donors to male C57BL/6 recipients and treated with CAP for seven days. The rejection of these heart transplants was assessed using a range of techniques, including H&E staining, immunohistochemistry, RNA sequencing, LS-MS/MS, and flow cytometry. In vitro, naïve CD4+ T cells were isolated and cultured under Th1 condition medium with varying treatments, flow cytometry, LS-MS/MS were employed to delineate the role of thymidine synthase (TYMS) during Th1 differentiation. Results CAP treatment significantly mitigated acute allograft rejection and enhanced graft survival by reducing graft damage, T cell infiltration, and levels of circulating pro-inflammatory cytokines. Additionally, it curtailed CD4+ T cell proliferation and the presence of Th1 cells in the spleen. RNA-seq showed that TYMS, the target of CAP, was robustly increased post-transplantation in splenocytes. In vitro, TYMS and its metabolic product dTMP were differentially expressed in Th0 and Th1, and were required after activation of CD4+ T cell and Th1 differentiation. TYMS-specific inhibitor, raltitrexed, and the metabolite of capecitabine, 5-fluorouracil, could inhibit the proliferation and differentiation of Th1. Finally, the combined use of CAP and the commonly used immunosuppressant rapamycin can induce long-term survival of allograft. Conclusion CAP undergoes metabolism conversion to interfere pyrimidine metabolism, which targets TYMS-mediated differentiation of Th1, thereby playing a significant role in mitigating acute cardiac allograft rejection in murine models.

At present, although there are tumor markers for hepatocellular carcinoma (HCC), markers with better predictive efficiency are needed. SAA4 gene expression in liver tumor and paracancerous tissues was analyzed using The Cancer Genome Atlas database. The differentially expressed genes (DEGs) were analyzed and visualized by heatmap and volcano plot. Survival analysis was performed based on SAA4 expression. SAA4 expression was compared in patients grouped based on clinicopathological features, and gene set enrichment analysis (GSEA) was conducted. Immunohistochemical staining was used to verify the SAA4 protein staining intensity from The Human Protein Atlas database and our center’s samples. The diagnostic value of SAA4 for HCC was evaluated by receiver operating characteristic curves. SAA4 was expressed at low levels in HCC tissues, and low SAA4 expression was associated with a poor prognosis in HCC. In addition, SAA4 expression decreased with HCC progression. There were 188 upregulated DEGs and 1551 downregulated DEGs between the high and low SAA4 expression groups. Complement and coagulation cascades, fatty acid metabolism, and ECM receptor interaction were significantly enriched in the GSEA. SAA4 had good predictive efficacy for HCC and even early HCC and was superior to AFP. In general, low SAA4 expression was associated with advanced HCC stage and a poor prognosis. In addition, SAA4 may be helpful for the diagnosis of early HCC and may become a novel tumor marker with good predictive power for HCC.

目的 研究胆道闭锁患儿肝外门静脉管壁增厚的病理形态学特征,同时探讨肝外门静脉管壁增厚程度的临床意义及危险因素.方法 分析2022年6月至2022年12月天津市第一中心医院儿童器官移植科60例行肝移植治疗的胆道闭锁患儿的临床病理资料,观察胆道闭锁患儿肝外门静脉管壁增厚的病理形态学改变.根据肝外门静脉总管壁厚度的中位数,将胆道闭锁患儿分为门静脉轻度增厚组及门静脉重度增厚组.比较两组间Kasai术后自体肝生存时间.单因素和多因素Logistic回归分析肝外门静脉管壁增厚程度的影响因素.结果 胆道闭锁患儿肝外门静脉管壁出现不同程度增厚,以血管内皮细胞下间质水肿、纤维和成纤维细胞增生及少量炎细胞浸润为主要病理学改变.肝外门静脉管壁内膜厚度为110(30～640)μm,总管壁厚度为373(160～1320)μm,门静脉内膜厚度/门静脉总管壁厚度的比值0.341(0.105～0.636).对胆道闭锁进行分组,总管壁厚度≤373 μm定义为门静脉轻度增厚组,总管壁厚度＞373 μm定义为门静脉重度增厚组.门静脉重度增厚组自体肝生存时间显著低于门静脉轻度增厚组,差异有统计学意义(P＜0.05).单因素分析结果显示:Kasai手术史和胆管炎病史是影响胆道闭锁肝外门静脉管壁增厚程度的相关因素(P＜0.05).多因素分析结果显示:胆管炎病史是影响胆道闭锁肝外门静脉管壁增厚程度的独立危险因素(优势比=4.000,95%可信区间=1.272～12.578,P＜0.05).结论 胆道闭锁患儿肝外门静脉管壁增厚以血管内皮细胞下间质水肿、纤维和成纤维细胞增生及少量炎细胞浸润为主要特征.胆道闭锁肝外门静脉管壁增厚程度可能影响Kasai术后自体肝生存时间.预防并治疗胆管炎,有助于减轻门静脉管壁增厚的程度.

人肝类器官由于具有与靶器官类似的结构与功能,且可在体外稳定的长期培养、扩增与冻存,因而在多个领域发挥着越来越重要的作用.基于类器官技术的肝类器官生物样本库也应运而生.为了全面概述肝类器官生物样本库的构建情况,本文首先综述了常见的肝类器官构建技术,进一步阐述了肝类器官生物样本库建设需考虑的关键要素,最后展望了其未来的发展方向,以期推动我国肝类器官生物样本库的建设与发展.

Liver transplantation is one of the most effective treatments for hepatocellular carcinoma (HCC). The balance between inhibiting immune rejection and preventing tumor recurrence after liver transplantation is the key to determining the long-term prognosis of patients with HCC after liver transplantation. In our previous study, we found that capecitabine (CAP), an effective drug for the treatment of HCC, could exert an immunosuppressive effect after liver transplantation by inducing T cell ferroptosis. Recent studies have shown that ferroptosis is highly associated with autophagy. In this study, we confirmed that the autophagy inducer rapamycin (RAPA) combined with metronomic capecitabine (mCAP) inhibits glutathione peroxidase 4 (GPX4) and promotes ferroptosis in CD4+ T cells to exert immunosuppressive effects after rat liver transplantation. Compared with RAPA or mCAP alone, the combination of RAPA and mCAP could adequately reduce liver injury in rats with acute rejection after transplantation. The CD4+ T cell counts in peripheral blood, spleen, and transplanted liver of recipient rats significantly decreased, and the oxidative stress level and ferrous ion concentration of CD4+ T cells significantly increased in the combination group. In vitro, the combination of drugs significantly promoted autophagy, decreased GPX4 protein expression, and induced ferroptosis in CD4+ T cells. In conclusion, the autophagy inducer RAPA improved the mCAP-induced ferroptosis in CD4+ T cells. Our results support the concept of ferroptosis as an autophagy-dependent cell death and suggest that the combination of ferroptosis inducers and autophagy inducers is a new research direction for improving immunosuppressive regimens after liver transplantation.

DnDSAs in pediatric liver transplant recipients are associated with liver transplant rejection and fibrosis. The level of dnDSAs in low risk group should not be disregarded. Routine detection of dnDSAs has clinical utility for noninvasive risk stratification in this population.

BACKGROUND:This study aimed to explore whether serum CXCL8 concentration can be used as a noninvasive marker of subclinical rejection (SCR) after pediatric liver transplantation (pLT).METHODS:Firstly, RNA sequencing (RNA-seq) was performed on 22 protocol liver biopsy samples. Secondly, several experimental methods were used to verify the RNA-seq results. Finally, the clinical data and serum samples of 520 LT patients in the Department of Pediatric Transplantation of Tianjin First Central Hospital from January 2018 to December 2019 were collected.RESULTS:RNA-seq results indicated that CXCL8 was significantly increased in the SCR group. The results of the 3 experimental methods were consistent with RNA-seq results. According to the 1:2 propensity score matching, 138 patients were divided into the SCR (n = 46) and non-SCR (n = 92) groups. Serological test results indicated that there was no difference in preoperative CXCL8 concentration between the SCR and non-SCR groups ( P  > 0.05). However, during protocol biopsy, CXCL8 in the SCR group was significantly higher than in the non-SCR group ( P  < 0.001). In diagnosing SCR, receiver operating characteristic curve analysis showed that the area under the curve of CXCL8 was 0.966 (95% confidence interval, 0.938-0.995), sensitivity was 95%, and specificity was 94.6%. In differentiating nonborderline from borderline rejection, the area under the curve of CXCL8 was 0.853 (95% confidence interval, 0.718-0.988), sensitivity was 86.7%, and specificity was 94.6%.CONCLUSIONS:This study demonstrates that serum CXCL8 concentration has high accuracy for the diagnosis and disease stratification of SCR after pLT.