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Abstract Chemokine (C-X3-C motif) Receptor 1 (CX3CR1) primarily mediates the chemotaxis and adhesion of immune cells. However, its role in hepatitis C virus (HCV)-induced early-stage liver cirrhosis remains unexplored. GSE15654 was downloaded from the GEO database. The Cox regression model, CIBERSORT, and LASSO technique were utilized to identify CX3CR1-associated immune infiltration genes (IIGs). Surgical resection samples were collected for verification, including 3 healthy controls (HC), 4 individuals with HCV-induced hepatic cirrhosis, and 3 with HCV-induced liver failure. High CX3CR1 expression correlated with worse prognosis in early-stage cirrhosis. CX3CR1-associated IIGs, namely ACTIN4, CD1E, TMCO1, and WSF1, were identified, showing specific expression in the livers of individuals with post-hepatic cirrhosis and liver failure compared to HC. LOC400499 and MTHFD2 were elevated in individuals with liver failure in comparison to those with hepatocirrhosis. Notably, high infiltration of plasma cells and low infiltration of monocytes were predictive of poor prognosis in early-stage cirrhosis. The combined risk model predicted that high expression of CX3CR1-associated IIGs and increased infiltration of plasma cells were associated with unfavorable prognosis in individuals with HCV-induced early-stage liver cirrhosis. The developed combined risk model effectively predicted the prognosis of these individuals.

Abstract Background Epilepsy is a major global health challenge, affecting approximately 50 million people across the globe and resulting in significant economic impacts on individuals and society. Oxidative stress is implicated in the pathogenesis of epilepsy, highlighting the potential of antioxidant-rich dietary patterns in offering preventive and protective benefits by mitigating oxidative stress. The Composite Dietary Antioxidant Index (CDAI) provides a measure for assessing dietary antioxidant intake, yet its link to epilepsy remains unexplored. Methods Our analysis utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 2013 to 2018, including 20,180 screened participants. Weighted logistic regression models were employed to examine the association between the CDAI and epilepsy prevalence. Non-linear associations were explored through restricted cubic splines (RCS), and the relationships between individual antioxidant components within the CDAI and epilepsy were also assessed. Results After adjusting for potential confounders, a negative association between the CDAI and epilepsy was suggested (OR = 0.991; p = 0.087, 95% CI [0.819,1.014]). Stratification of CDAI into quartiles revealed a significantly reduced risk of epilepsy in higher CDAI quartiles (Q3 and Q4) compared to the lowest quartile (Q1) (Q3: OR = 0.419; p = 0.030, 95% CI [0.192, 0.914]; Q4: OR = 0.421; p = 0.004, 95% CI [0.239, 0.742]), with a significant trend observed across quartiles (p for trend = 0.013). RCS analysis suggested a nonlinear association between CDAI levels and epilepsy (non-linear p = 0.049), which, however, was not statistically significant after full adjustment (non-linear p = 0.103). Additionally, significant negative correlations with epilepsy were observed for vitamin A and zinc (Vitamin A: OR = 0.999; p = 0.012, 95% CI [0.998, 1.000]; Zinc: OR = 0.931; p = 0.042, 95% CI [0.869, 0.997]). Conclusions Our research indicates a correlation where higher CDAI levels correspond to a reduced risk of epilepsy. Therefore, embracing a diet rich in antioxidants could be beneficial in preventing epilepsy. This finding holds considerable potential for shaping future strategies in both epilepsy prevention and treatment.

Accurately identifying user needs in terms of assist timing and magnitude presents challenges for wearable power‐assist limb devices. Traditional approaches to gait perception—such as estimating joint angles and walking conditions—often rely on electronic sensors and neural networks, which can compromise wearability and impose high computational demands. Physical reservoir computing (PRC), which utilizes the inherent nonlinearity of physical systems for data processing, offers a promising alternative. This study proposes a novel self‐estimated physical reservoir computing (SEPRC) model that improves traditional PRC models for gait perception using a wearable pneumatic physical reservoir. A core feature of the new model is the self‐estimation structure, wherein the outputs of the physical reservoir are mutually estimated. Experimental evaluations indicate that the SEPRC model outperforms traditional PRC in clustering time‐series reservoir output sequences with the same dimensionality. This enhanced clustering performance is subsequently leveraged in gait perception by incorporating Takagi–Sugeno fuzzy logic for joint angle estimation and a softmax activation function for walking condition recognition. The newly proposed time‐sequence processing approach facilitates the traditional PRC model to achieve higher accuracy in gait perception and greater robustness against the user's walking pattern variations while preserving PRC's hardware simplicity.

Abstract Background The high recurrence rate after liver resection emphasizes the urgent need for neoadjuvant therapy in hepatocellular carcinoma (HCC) to enhance the overall prognosis for patients. Immune checkpoint inhibitors, camrelizumab combined with an anti-angiogenic tyrosine kinase inhibitor (TKI) apatinib, have emerged as a first-line treatment option for patients with unresectable HCC, yet its neoadjuvant application in combination with transarterial chemoembolization (TACE) in HCC remains unexplored. Therefore, this study aims to investigate the efficacy and safety of sequential TACE, camrelizumab, and apatinib as a neoadjuvant therapy for single, huge HCC. Methods This multi-center, open-label randomized phase 3 trial will be conducted at 7 tertiary hospitals. Patients with single huge (≥ 10 cm in diameter), resectable HCC will be randomly assigned in a 1:1 ratio to arm of surgery alone or arm of neoadjuvant therapy followed by surgery. In the neoadjuvant therapy group, patients will receive TACE within 1 week after randomization, followed by camrelizumab (200 mg q2w, 4 cycles), along with apatinib (250 mg qd, 2 months). Patients will receive liver resection after neoadjuvant therapy unless the disease is assessed as progressive. The primary outcome is recurrence-free survival (RFS) at 1 year. The planned sample size of 60 patients will be calculated to permit the accumulation of sufficient RFS events in 1 year to achieve 80% power for the RFS primary endpoint. Discussion Synergistic effects provided by multimodality therapy of locoregional treatment, TKI, and anti-programmed cell death 1 inhibitor significantly improved overall survival for patients with unresectable HCC. Our trial will investigate the efficacy and safety of the triple combination of TACE, camrelizumab, and apatinib as a neoadjuvant strategy for huge, resectable HCC. Trial registration www.chitr.org.cn ChiCTR2300078086. Registered on November 28, 2023. Start recruitment: 1st January 2024. Expected completion of recruitment: 15th June 2025.

Abstract Posttransplantation complications pose a major challenge to the long‐term survival and quality of life of organ transplant recipients. These complications encompass immune‐mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation. Here, we provide a comprehensive overview of the clinical features, risk factors, and molecular mechanisms of major posttransplantation complications. We systematically summarize the current understanding of the immunological basis of allograft rejection and graft‐versus‐host disease, the metabolic dysregulation associated with immunosuppressive agents, and the role of oncogenic viruses in posttransplantation malignancies. Furthermore, we discuss potential prevention and intervention strategies based on these mechanistic insights, highlighting the importance of optimizing immunosuppressive regimens, enhancing infection prophylaxis, and implementing targeted therapies. We also emphasize the need for future research to develop individualized complication control strategies under the guidance of precision medicine, ultimately improving the prognosis and quality of life of transplant recipients.

Nocardia farcinica is an aerobic gram-positive bacterium that is pathogenic to humans. It usually causes local and adjacent tissues’ diseases at the entry of infection (most commonly occur in the lungs, skin, or central nervous system), which can also spread to other organs through the bloodstream such as joints, kidneys, and liver. However, these infections are often seen as opportunistic that occur in immunocompromised patients. Here, we report for the first time two immunocompetent patients lacking evidence of local infections, with multiple lymph node enlargements and fever as main clinical manifestations, finally diagnosed as nocardiosis by Metagenomic Next-Generation Sequencing testing (mNGS) from formalin-fixed and paraffin-embedded (FFPE) lymph node tissue, after all the other standard tests were negative. Both patients recovered after receiving anti-nocardia therapies. These two cases indicates that in healthy population, there may be more potential nocardia infections than we expected. Multiple lymph node enlargements and fever suggest a possibility of nocardiosis, especially in patients with fever of unknown origin (FUO). mNGS detection from FFPE lymph node tissue is an accurate, reliable and traceable method for diagnosis of nocardiosis.

Abstract Rheumatoid arthritis (RA) is a persistent autoimmune condition characterized by synovitis and joint damage. Recent findings suggest a potential link to abnormal lactate metabolism. This study aims to identify lactate metabolism-related genes (LMRGs) in RA and investigate their correlation with the molecular mechanisms of RA immunity. Data on the gene expression profiles of RA synovial tissue samples were acquired from the gene expression omnibus (GEO) database. The RA database was acquired by obtaining the common LMRDEGs, and selecting the gene collection through an SVM model. Conducting the functional enrichment analysis, followed by immuno-infiltration analysis and protein–protein interaction networks. The results revealed that as possible markers associated with lactate metabolism in RA, KCNN4 and SLC25A4 may be involved in regulating macrophage function in the immune response to RA, whereas GATA2 is involved in the immune mechanism of DC cells. In conclusion, this study utilized bioinformatics analysis and machine learning to identify biomarkers associated with lactate metabolism in RA and examined their relationship with immune cell infiltration. These findings offer novel perspectives on potential diagnostic and therapeutic targets for RA.

Summary: Background: The FDA's alerts regarding the T-cell lymphoma risk post CAR-T therapy has garnered global attention, yet a comprehensive profile of second primary malignancies (SPMs) following CAR-T treatment is lacking. Methods: We extracted adverse event reports of hematological malignancies (HMs) patients with clearly definable SPMs from the FAERS and VigiBase databases (2017–2023). Disproportionality analysis using reporting odds ratio (ROR) and adjusted ROR was performed to assess associations between SPMs and CAR-T therapy. Time-to-onset analysis explored factors affecting SPM manifestation. Findings: SPMs post CAR T-cell therapy include HMs and solid tumors. T-cell lymphoma and myelodysplastic syndromes were consistently identified as positive signals across the overall and subgroup analyses. Hematological SPMs showed earlier onset with increasing annual incidence post CAR-T therapy, whereas solid tumors exhibit delayed manifestation. SPMs in CAR-T recipients had significantly earlier onset than non-recipients. Furthermore, age-specific characteristics reveal earlier SPM manifestations in pediatric, adolescent, and young adult populations compared to older populations post CAR-T therapy. Interpretation: The current SPM profile highlights the necessity of long-term safety monitoring for all CAR-T recipients given the observed yearly increase of SPMs. Customizing long-term SPM screening across different age groups may enhance early detection and intervention strategies, ultimately improving patient outcomes in the follow-up of CAR-T recipients. Funding: This work was supported by grants from the Natural Science Foundation of Guangdong Province (2018A030313846 and 2021A1515012593), the Science and Technology Planning Project of Guangdong Province (2019A030317020), the National Natural Science Foundation of China (81802257, 81871859, 81772457, 82172750, 82172811, and 82260546), the Guangdong Basic and Applied Basic Research Foundation (Guangdong–Guangzhou Joint Funds) (2022A1515111212), and the Science and Technology Program of Guangzhou (2023A04J1257).

The mechanical environment of vascular endothelial cells (ECs) encompasses a wide range of curvatures due to variations in blood vessel diameters. Integrins, key mediators of cell-matrix interactions, establish connections between the extracellular matrix and the actin cytoskeleton, influencing diverse cellular behaviors. In this study, we explored the impact of spatial confinement on human umbilical vein ECs (HUVECs) cultured within three-dimensional hydrogel microgrooves of varying curvatures and the underlying role of integrins in mediating cellular responses. Employing maskless lithography, we successfully fabricated precise and wall curvatures-controlled hydrogel microgrooves, conferring spatial constraints on the cells. Our investigations revealed substantial alterations in HUVEC behavior within the hydrogel microgrooves with varying sidewall curvatures, marked by reduced cell size, enhanced orientation, and increased apoptosis. Interestingly, microgroove curvature emerged as a crucial factor influencing cell orientation and apoptosis, with rectangular microgrooves eliciting distinct changes in cell orientation, while ring-form microgrooves exhibited higher apoptosis rates. The side-wall effect in the 20 μm region near the microgroove wall had the greatest influence on cell orientation and apoptosis. HUVECs within the microgrooves exhibited elevated integrin expression, and inhibition of αV-integrin by cilengitide significantly curtailed cell apoptosis without affecting proliferation. Additionally, integrin-mediated cell traction force closely correlated with the spatial confinement effect. Cilengitide not only reduced integrin and focal adhesion expression but also attenuated cell traction force and cytoskeletal actin filament alignment. Overall, our findings elucidate the spatial confinement of ECs in hydrogel microgrooves and underscores the pivotal role of integrins, particularly αV-integrin, in mediating cell traction force and apoptosis within this microenvironment.

Background: As a fatal disease, cytokine storm has garnered research attention in recent years. Nonetheless, as the body of related studies expands, a thorough and impartial evaluation of the current status of research on cytokine storms remains absent. Consequently, this study aimed to thoroughly explore the research landscape and evolution of cytokine storm utilizing bibliometric and knowledge graph approaches. Methods: Research articles and reviews centered on cytokine storms were retrieved from the Web of Science Core Collection database. For bibliometric analysis, tools such as Excel 365, CiteSpace, VOSviewer, and the Bibliometrix R package were utilized. Results: This bibliometric analysis encompassed 6647 articles published between 2004 and 2022. The quantity of pertinent articles and citation frequency exhibited a yearly upward trend, with a sharp increase starting in 2020. Network analysis of collaborations reveals that the United States holds a dominant position in this area, boasting the largest publication count and leading institutions. Frontiers in Immunology ranks as the leading journal for the largest publication count in this area. Stephan A. Grupp, a prominent researcher in this area, has authored the largest publication count and has the second-highest citation frequency. Research trends and keyword evaluations show that the connection between cytokine storm and COVID-19, as well as cytokine storm treatment, are hot topics in research. Furthermore, research on cytokine storm and COVID-19 sits at the forefront in this area. Conclusion: This study employed bibliometric analysis to create a visual representation of cytokine storm research, revealing current trends and burgeoning topics in this area for the first time. It will provide valuable insights, helping scholars pinpoint critical research areas and potential collaborators.

Abstract Background Liver fibrosis contributes to significant morbidity and mortality in Western nations, primarily attributed to chronic hepatitis C virus (HCV) infection. Hypoxia and immune status have been reported to be significantly correlated with the progression of liver fibrosis. The current research aimed to investigate the gene signature related to the hypoxia-immune-related microenvironment and identify potential targets for liver fibrosis. Method Sequencing data obtained from GEO were employed to assess the hypoxia and immune status of the discovery set utilizing UMAP and ESTIMATE methods. The prognostic genes were screened utilizing the LASSO model. The infiltration level of 22 types of immune cells was quantified utilizing CIBERSORT, and a prognosis-predictive model was established based on the selected genes. The model was also verified using qRT-PCR with surgical resection samples and liver failure samples RNA-sequencing data. Results Elevated hypoxia and immune status were linked to an unfavorable prognosis in HCV-induced early-stage liver fibrosis. Increased plasma and resting NK cell infiltration were identified as a risk factor for liver fibrosis progression. Additionally, CYP1A2, CBS, GSTZ1, FOXA1, WDR72 and UHMK1 were determined as hypoxia-immune-related protective genes. The combined model effectively predicted patient prognosis. Furthermore, the preliminary validation of clinical samples supported most of the conclusions drawn from this study. Conclusion The prognosis-predictive model developed using six hypoxia-immune-related genes effectively predicts the prognosis and progression of liver fibrosis. The current study opens new avenues for the future prediction and treatment of liver fibrosis.

Abstract The Uncanny Valley hypothesis implies that people perceive a subjective border between human and robot faces. The robot–human border refers to the level of human-like features that distinguishes humans from robots. However, whether people’s perceived anthropomorphism and robot–human borders are consistent across different robot occupations remains to be explored. This study examined the robot–human border by analyzing the human photo proportion represented by the point of subjective equality in three image classification tasks. Stimulus images were generated by morphing a robot face photo and one each of four human photos in systematically changed proportions. Participants classified these morphed images in three different robot occupational conditions to explore the effect of changing robot jobs on the robot–human border. The results indicated that robot occupation and participant age and gender influenced people’s perceived anthropomorphism of robots. These can be explained by the implicit link between robot job and appearance, especially in a stereotyped context. The study suggests that giving an expected appearance to a robot may reproduce and strengthen a stereotype that associates a certain appearance with a certain job.

Abstract Background Disrupted sleep is believed to contribute to short- and long-term neurodevelopmental problems in very preterm infants (VPIs). This study presents a protocol for an evaluator-blinded, randomized crossover trial. It aims to assess the sleep efficiency of hospitalized VPIs by providing multisensory stimulation bundles. Furthermore, it aims to observe the intervention impacts on sleep during hospitalization of the VPIs and their sleep and neurodevelopmental outcomes during the first year of post-discharge follow-up. Methods The study will be conducted in the neonatology department of a tertiary pediatric teaching hospital. All the eligible VPIs will undergo two types of care in random order: “standard care” (2 weeks) and “standard care plus multisensory stimulation bundles,” each lasting 2 weeks. A generated list of random numbers will be used for case sequence allocation. Sleep outcomes will be evaluated using the Actiwatch-2 Actigraph. Moreover, the amplitude-integrated electroencephalography and the Griffiths Mental Development Scales will be used to measure the neurodevelopmental outcomes during hospitalization and in the first year of follow-up of the VPIs. Discussion The intervention protocol of this study differs from that of other traditional interventions by producing precise and consistent supportive stimulations, similar to maternal tactile, auditory, posture, and visual effects for hospitalized VPIs. This protocol could be an effective measure to facilitate sleep and early neurodevelopment of VPIs. The expected outcomes will help confirm the implementation and generalization of the multisensory stimulation bundles’ care protocol in neonatology departments. We expect that the study will positively impact hospitalized VPIs, especially in their sleep and early neurodevelopmental outcomes. It will also provide a new perspective regarding parent and infant interaction strategies, particularly for newborn intensive care units that limit visits because of the global spread of COVID-19. Trial registration Chinese Clinical Trial Registry ChiCTR 2200059099. Registered on 25 April 2022, https://www.chictr.org.cn/showproj.html?proj=166980 ; the Hospital Research Ethics Committee (approval number: SCMCIRB-K2021086-1, Version 01), approved on 21 January 2022.

Abstract. Background:. Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear. Methods:. We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted. Results:. Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS−) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS− hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS− patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways. Conclusions:. GS− HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.

In dynamic complex environments, it is inevitable for UAVs to be damaged due to their confrontational nature. The challenge to minimize the adverse effects of the damage and reallocate the mission is vital for achieving the operational goal. This paper proposes a distributed Multi-UAV mission reallocation method in the case of UAV damage based on the improved consensus-based bundle algorithm (CBBA). Firstly, a dynamic optimization model for Multi-UAV mission reallocation is established based on an improved resource update model. Secondly, a distributed damage inspection method based on the heartbeat hold mechanism is proposed for real-time monitoring of UAV conditions, which could enable the rapid response to UAV damage events. Furthermore, the CBBA is improved by introducing a timeliness parameter to adjust the bidding strategy and optimizing the mission selection strategy based on the time-order priority insertion principle to generate mission reallocation plans quickly. Through numerical examples, the results show that the proposed method can effectively reallocate Multi-UAV missions under damage events and has superior performance compared with original the CBBA, the particle swarm optimization (PSO) algorithm, and the performance impact (PI) algorithm. The proposed method has a faster solving speed, while the obtained solution has higher mission reallocation effectiveness.

Abstract Aims This study aimed to evaluate the clinical significance of the preoperative aminotransferase to albumin ratio (AAR) in patients with hepatocellular carcinoma (HCC) after hepatectomy. Methods From five hospitals, a total of 991 patients with HCC admitted between December 2014 and December 2019 were included as the primary cohort and 883 patients with HCC admitted between December 2010 and December 2014 were included as the validation cohort. The X-tile software was conducted to identify the optimal cut-off value of AAR. Results In the primary cohort, the optimal cut-off value of the AAR was defined as 0.7 and 1.6, respectively. Compared to patients with AAR 0.7–1.6, those with AAR > 1.6 showed significantly worse overall survival (OS) and RFS, whereas those with AAR 1.6 had more aggressive tumour characteristics, such as larger tumour size, higher incidence of microvascular invasion, and severe histologic activity, and higher AFP level than patients with AAR

BackgroundMelanoma is a skin tumor with a high mortality rate, and early diagnosis and effective treatment are the key to reduce its mortality rate. Therefore, more and more attention has been paid for biomarker identification for early diagnosis, prognosis prediction and prognosis evaluation of melanoma. However, there is still a lack of a report that comprehensively and objectively evaluates the research status of melanoma biomarkers. Therefore, this study aims to intuitively analyze the research status and trend of melanoma biomarkers through the methods of bibliometrics and knowledge graph.ObjectiveThis study uses bibliometrics to analyze research in biomarkers in melanoma, summarize the field’s history and current status of research, and predict future research directions.MethodArticles and Reviews related to melanoma biomarkers were retrieved by using Web of Science core collection subject search. Bibliometric analysis was performed in Excel 365, CiteSpace, VOSviewer and Bibliometrix (R-Tool of R-Studio).ResultA total of 5584 documents from 2004 to 2022 were included in the bibliometric analysis. The results show that the number of publications and the frequency of citations in this field are increasing year by year, and the frequency of citations has increased rapidly after 2018. The United States is the most productive and influential country in this field, with the largest number of publications and institutions with high citation frequency. Caroline Robert, F. Stephen Hodi, Suzanne L. Topalian and others are authoritative authors in this field, and The New England Journal of Medicine, Journal of Clinical Oncology and Clinical Cancer Research are the most authoritative journals in this field. Biomarkers related to the diagnosis, treatment and prognosis of melanoma are hot topics and cutting-edge hotspots in this field.ConclusionFor the first time, this study used the bibliometric method to visualize the research in the field of melanoma biomarkers, revealing the trends and frontiers of melanoma biomarkers research, which provides a useful reference for scholars to find key research issues and partners.

PurposeTo explore the safety and efficacy of lenvatinib in combination with trans-arterial chemoembolization (TACE) and programmed death receptor 1 (PD-1) antibody in the treatment of unresectable recurrent hepatocellular carcinoma (urHCC).Patients and methodsThe clinical data of 16 patients with unresectable recurrent hepatocellular carcinoma admitted to the Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, and received the conversion therapy of lenvatinib + TACE + PD-1 antibody between January 2019 and January 2022 were retrospectively analyzed.ResultsThere were 25% (4/16) patients suffering from grade 3 adverse events and no patients suffering from grade 4 or higher adverse events. After 4 months of treatment of 16 patients, according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), two, five, three, and six cases were in complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), respectively, and the objective response rate (ORR) was 43.8% (7/16). The 1-year overall survival (OS) rate and 1-year progression-free survival (PFS) rate were 86.2% and 46.9%, respectively. In our subgroup analysis, the ORR of patients with multiple lesions reached up to 60%, which was higher than that of patients with single lesions.ConclusionsLenvatinib in combination with TACE and PD-1 antibody is safe and effective in the treatment of unresectable recurrent hepatocellular carcinoma.

Pharmacological inhibition of the prolyl isomerase PIN1, highly expressed in cancer cells and cancer associated fibroblasts (CAF), has been proposed for cancer therapy. Here the authors report the design of a DNA-barcoded micellular system functionalized with antibodies targeting CAFs and a T cell recruiting aptamer to deliver the PIN1 inhibitor AG17724, showing antitumor response in preclinical models of pancreatic cancer.

Abstract Background Previous studies have reported the surgical resection (SR) and radiofrequency ablation (RFA) could achieve comparable recurrence-to-death survival (RTDS). However, the impact of primary tumor burden on RTDS of patients with recurrent hepatocellular carcinoma (HCC) following SR or RFA has not been clarified. Methods From January 2009 to March 2015, 171 patients who underwent initial hepatectomy and second curative treatments in West China Hospital were retrospectively analyzed. Survival analysis was performed by the Kaplan–Meier method. Risk factors were identified using the Cox proportional hazard model. Results At initial hepatectomy, 96 patients (56.1%) were diagnosed with HCC within the Milan criteria (MC), and 75 patients (43.9%) were HCC beyond the MC. The clinicopathological features and re-treatment methods of recurrent HCC were similar between patients with primary HCC within or beyond the MC. Patients with primary HCC within the MC had longer recurrence time (31.4 ± 24.2 months vs. 20.2 ± 16 months, P 400 ng/mL at the time of recurrence were associated with RTDS. Conclusions The primary tumor burden had no impact on RTDS, but had an impact on recurrence time. The recurrence time had an impact on RTDS and might be a good index to reflect the biology of recurrent HCC.

Abstract. Background:. Hepatectomy for hepatocellular carcinoma (HCC) beyond the Milan criteria is shown to be beneficial. However, a high rate of post-operative HCC recurrence hinders the long-term survival of the patients. This study aimed to investigate and compare the impacts of tenofovir (TDF) and entecavir (ETV) on the recurrence of hepatitis B viral (HBV)-related HCC beyond the Milan criteria. Methods:. Data pertaining to 1532 patients who underwent hepatectomy and received antiviral therapy between January 2014 and January 2019 were collected from five centers. Recurrence-free survival (RFS) analysis was performed using the Kaplan–Meier method. Cox proportional hazards regression analysis was performed to determine prognostic factors for HCC recurrence. Results:. The analysis incorporates 595 HBV-related HCC patients. The overall 5-year RFS was 21.3%. Among them, 533 and 62 patients received ETV and TDF treatment, respectively. The 1-, 3-, and 5-year RFS rates were 46.3%, 27.4%, and 19.6%, respectively, in the ETV group compared with 65.1%, 41.8%, and 37.2%, respectively, in the TDF group (P

Atherosclerosis is an inflammatory disease initiated by endothelial activation, in which lipoprotein, cholesterol, extracellular matrix, and various types of immune and non-immune cells are accumulated and formed into plaques on the arterial wall suffering from disturbed flow, characterized by low and oscillating shear stress. Foam cells are a major cellular component in atherosclerotic plaques, which play an indispensable role in the occurrence, development and rupture of atherosclerotic plaques. It was previously believed that foam cells were derived from macrophages or smooth muscle cells, but recent studies have suggested that there are other sources of foam cells. Many studies have found that the distribution of atherosclerotic plaques is not random but distributed at the bend and bifurcation of the arterial tree. The development and rupture of atherosclerotic plaque are affected by mechanical stress. In this review, we reviewed the advances in foam cell formation in atherosclerosis and the regulation of atherosclerotic plaque and lipid metabolism by mechanical forces. These findings provide new clues for investigating the mechanisms of atherosclerotic plaque formation and progression.

Abstract Background Antiviral therapy should reduce the recurrence of hepatitis B virus‐related hepatocellular carcinoma (HBV‐related HCC) after surgical resection. However, there is little research on whether various antiviral drugs have different prognostic effects in patients with HBV‐related HCC after curative liver resection. The present study compared the effects of nucleotide analog (NtA) and nucleoside analog (NsA) antiviral therapies after surgical resection on the prognosis of HBV‐related HCC. Methods A total of 1303 patients with HBV‐related HCC who received curative hepatectomy at five institutes between April 2014 and April 2019 were retrospectively enrolled and analyzed. Propensity matching analysis was used to compare the outcomes of HCC patients given NsA versus NtA therapy. Subgroup analysis of patients treated with entecavir (ETV) and tenofovir disoproxil fumarate (TDF) was also performed. Results Among 1303 patients, 759 (58.2%) patients developed recurrence, and 460 (35.3%) patients died. Multivariable analyses revealed that NtA therapy significantly decreased the risk of HCC recurrence (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.51–0.80; p

BackgroundNeutrophil extracellular traps (NETs) are specialized structures formed by neutrophils that were initially found to be important in killing pathogenic bacteria during infection. With the development of related research, the relationship between NETs and diseases such as sepsis, cancer, and systemic lupus erythematosus has received close attention. However, there is a lack of reports that comprehensively and objectively present the current status of NETs-related studies. Therefore, this study aims to visually analyze the current status and trends of NETs-related research by means of bibliometrics and knowledge mapping.MethodsNETs-related articles and reviews were retrieved using the Web of Science core collection subject search, and bibliometric analysis was performed in Excel 365, CiteSpace, VOSviewer, and Bibliometrix (R-Tool of R-Studio).ResultsA total of 4866 publications from 2004 to 2022 were included in the bibliometric analysis. The number of publications shows an increasing trend from year to year. Collaborative network analysis shows that the United States and Germany are the most influential countries in this field, with the highest number of publications and citations. The journal with the most publications is Frontiers in Immunology. Brinkmann Volker is an authoritative author in this field, and his publication “Neutrophil extracellular traps kill bacteria” is the most frequently cited. The literature and keyword analysis shows that the relationship between NETs and diseases (hematological diseases, sepsis, cancer, etc.) and cell death (apoptosis, necroptosis, pyroptosis, etc.) is a popular research topic. Currently, NETs and SARS-CoV-2-related studies are at the forefront of the field.ConclusionThis study is the first to visualize the research in NETs-related fields using bibliometric methods, revealing the trends and frontiers of NETs research. This study will provide valuable references for scholars to find research focus questions and partners.

BackgroundIntestinal ischemia/reperfusion (I/R) injury is a common tissue-organ damage occurring in surgical practice. This study aims to comprehensively review the collaboration and impact of countries, institutions, authors, subject areas, journals, keywords, and critical literature on intestinal I/R injury from a bibliometric perspective, and to assess the evolution of clustering of knowledge structures and identify hot trends and emerging topics.MethodsArticles and reviews related to intestinal I/R were retrieved through subject search from Web of Science Core Collection. Bibliometric analyses were conducted on Excel 365, CiteSpace, VOSviewer, and Bibliometrix (R-Tool of R-Studio).ResultsA total of 1069 articles and reviews were included from 2004 to 2022. The number of articles on intestinal I/R injury gradually plateaued, but the number of citations increased. These publications were mainly from 985 institutions in 46 countries, led by China and the United States. Liu Kx published the most papers, while Chiu Cj had the largest number of co-citations. Analysis of the journals with the most outputs showed that most journals focused on surgical sciences, cell biology, and immunology. Macroscopic sketch and microscopic characterization of the entire knowledge domain were achieved through co-citation analysis. The roles of cell death, exosomes, intestinal flora, and anesthetics in intestinal I/R injury are the current and developing research focuses. The keywords “dexmedetomidine”, “proliferation”, and “ferroptosis” may also become new trends and focus of future research.ConclusionThis study comprehensively reviews the research on intestinal I/R injury using bibliometric and visualization methods, and will help scholars better understand the dynamic evolution of intestinal I/R injury and provide directions for future research.

Extracellular vesicles (EVs) are vesicles with a lipid bilayer membrane on the outside, which are widely found in various body fluids and contain biological macromolecules such as DNA, RNA, lipids and proteins on the inside. EVs were once thought to be vesicles for the removal of waste materials, but are now known to be involved in a variety of pathophysiological processes in many diseases. This study examines the advantage of EVs and the challenges associated with their application. A more rational use of the advantageous properties of EVs such as composition specificity, specific targeting, circulatory stability, active penetration of biological barriers, high efficient drug delivery vehicles and anticancer vaccines, oxidative phosphorylation activity and enzymatic activity, and the resolution of shortcomings such as isolation and purification methods, storage conditions and pharmacokinetics and biodistribution patterns during drug delivery will facilitate the clinical application of EVs.

Abstract Background Breast cancer lung metastasis occurs in more than 60% of all patients with breast cancer, and most of those afflicted by it eventually die of recurrence. The tumor microenvironment plays vital roles in metastasis. Modulating the tumor microenvironment via multiple pathways could efficiently prevent or inhibit lung metastasis. Silibinin and cryptotanshinone are natural plant products that demonstrate anti-metastasis effects and modulate the tumor microenvironment via different pathways. However, they have poor aqueous solubility, membrane permeability, and oral bioavailability. Oral drug administration may help improve the quality of life and compliance of patients with breast cancer, primarily under long-term and/or follow-up therapy. Herein, we developed poly-N-(2-hydroxypropyl) methacrylamide (pHPMA)-coated wheat germ agglutinin-modified lipid-polymer hybrid nanoparticles, co-loaded with silibinin and cryptotanshinone (S/C-pW-LPNs). We assessed their oral bioavailability, and evaluated their anti-metastasis efficacy in a 4T1 breast cancer tumor-bearing nude mouse model. Results An in vitro mucus diffusion study revealed that pHPMA enhanced W-LPN mucus penetration. After oral administration, pHPMA enhanced nanoparticle distribution in rat jejunum and substantially augmented oral bioavailability. S/C-W-LPNs markedly increased 4T1 cell toxicity and inhibited cell invasion and migration. Compared to LPNs loaded with either silibinin or cryptotanshinone alone, S/C-pW-LPNs dramatically slowed tumor progression in 4T1 tumor-bearing nude mice. S/C-pW-LPNs presented with the most robust anti-metastasis activity on smooth lung surfaces and mitigated lung metastasis foci. They also downregulated tumor microenvironment biomarkers such as CD31, TGF-β1, and MMP-9 that promote metastasis. Conclusions Silibinin- and cryptotanshinone-co-loaded pW-LPNs efficiently penetrate intestinal barriers, thereby enhancing the oral bioavailability of the drug loads. These nanoparticles exhibit favorable anti-metastasis effects in breast cancer-bearing nude mice. Hence, S/C-pW-LPNs are promising oral drug nanocarriers that inhibit breast cancer lung metastasis.

Background and AimsWith changes in dietary patterns and modern lifestyles, the prevalence of metabolic syndrome (MetS) in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) patients is increasing. The purpose of our study is to explore the impact of MetS on the prognosis of HBV-associated HCC patients following radical hepatectomy.MethodsData on consecutive HCC patients who underwent radical hepatectomy were prospectively obtained and retrospectively analyzed from seven medical centers in west areas of China. Propensity score matching (PSM) analysis was conducted to balance the heterogeneity between MetS-HBV-HCC group and HBV-HCC group. Surgical outcomes have been contrasted between the two groups.ResultsIn 984 patients, 179 (18.19%) were diagnosed with MetS. Patients in the MetS-HBV-HCC group had higher CCI score (8.7 [0.0, 12.2] vs. 0.0 [0.0, 8.7], p = 0.048) and a higher rate of severe complications (Clavien–Dindo ≥3, 7.82% vs. 4.10%, p = 0.035), to be more precise: postoperative liver failure, hydrothorax, and hyperglycemia. Patients in the MetS-HBV-HCC group tended to have worse 5-year overall survival (OS) rate (61.45% vs. 69.94%, p = 0.027) and recurrence-free survival (RFS) rate (62.57% vs. 53.66%, p = 0.030), consistent with the results of the competing risk models. Last, MetS was identified to be an independent unfavorable prognostic factor in the multivariate analysis.ConclusionThe involvement of MetS increased the risk of postoperative complications and worsens the overall survival and recurrence-free survival time, reminding us to be more prudent to face metabolic disorder among tumor patients.

Abstract Besides its well‐known benefits on human health, calcitriol, the hormonally active form of vitamin D3, has been being evaluated in clinical trials as an anticancer agent. However, currently available results are contradictory and not fundamentally deciphered. To the best of our knowledge, hypercalcemia caused by high‐dose calcitriol administration and its low bioavailability limit its anticancer investigations and translations. Here, we show that the one‐step self‐assembly of calcitriol and amphiphilic cholesterol‐based conjugates leads to the formation of a stable minimalist micellar nanosystem. When administered to mice, this nanosystem demonstrates high calcitriol doses in breast tumor cells, significant tumor growth inhibition and antimetastasis capability, as well as good biocompatibility. We further reveal that the underlying molecular antimetastatic mechanisms involve downregulation of proteins facilitating metastasis and upregulation of paxillin, the key protein of focal adhesion, in primary tumors.

After cerebral infarction, the regeneration of microvascular played an important role in the recovery. Ginsenoside Rg1 (Rg1) had good effects on promoting angiogenesis and neuro-protection in cerebral infarction treatment. However, the blood-brain barrier (BBB) restricted Rg1 to enter into cerebral tissue. Transferrin receptor (TfR) was over-expressed in the BBB. In this study, we fabricated a TfR targeting nano-carrier (PATRC) to penetrate the BBB for treatment of cerebral infarction. A TfR targeted peptide was conjugated with the nano-carrier wrapped hydrophobic Rg1. The nanoscale size (132 ± 12 nm), polydispersity index (PDI =0.29) and the zeta potential (−38mv) were tested with dynamic light scattering optical system. Surface morphology (ellipse, mean diameter 122 ± 26 nm) was detected by transmission electron microscope (TEM). PATRC implement cell targeting ability on rat brain microvascular endothelial cells RBE4 in vitro detected by immunofluorescence and flow cytometry methods. Comparing with Rg1 threated group, the PATRC exhibited more prominent ability on the tube formation ability (p

Abstract Background The aim of the study was to investigate the genetic risk factors of essential tremor (ET) in Chinese Population. Methods A total of 225 ET patients (25 ET patients also had restless legs syndrome (RLS) and were excluded from final analysis) and 229 controls were recruited. The diagnosis of ET was based on the Consensus Statement of the Movement Disorders Society on tremor. Polymerase chain reaction (PCR) and sequencing were used to detect 12 single nucleotide polymorphisms (SNPs) in seven candidate genes for RLS (HMOX1, HMOX2, VDR, IL17A, IL1B, NOS1 and ADH1B). Results We found that one SNP was associated with the risk of ET in Chinese population after adjusting for age and gender: rs1143633 of IL1B (odds ratio [OR] =2.57, p = 0.003, recessive model), and the statistical result remained significant after Bonferroni correction. Then, we performed a query in Genotype-tissue Expression (GTEx), Brain eQTL Almanac (Braineac) databases and Blood expression quantitative trait loci (eQTL) browser. The significant association was only found between genotype at rs1143633 and IL1B expression level of putamen and white matter in Braineac database, which was more prominent with homozygous (GG) carriers. Conclusions Our study firstly reported the association of IL1B polymorphism with the risk of ET in Chinese population. However, the association might only suggest a marker of IL1B SNP associated with ET instead of the casual variant. Further studies are needed to confirm our finding.

The data presented here contain information on cheating behavior from experiments and general self-reported attitudes related to honesty-related social norms and trust, together with individual-level demographic variables. Our sample included 493 university students in five countries, namely, Germany, Vietnam, Taiwan, China, and Japan. The experiment was monetarily incentivized based on the performance on a matrix task. The participants also answered a survey questionnaire. The dataset is valuable for academic researchers in sociology, psychology, and economics who are interested in honesty, norms, and cultural differences.

BackgroundLethal giant larvae (Lgl), scaffolding proteins, regulate the epithelial cell apicobasal polarity in Drosophila. They play important roles in asymmetric cell division, cell migration, and progenitor cells self-renewal as tumor suppressors. One of Lgl mammalian homologues proteins, LLGL2 overexpression has been reported in ER+ breast cancer and promotes tumor proliferation through regulating leucine uptake. Nonetheless, the role of LLGL2 in hepatocellular carcinoma (HCC) is still unknown.MethodsTCGA dataset mining, qRT-PCR, Western blot along with immunohistochemistry assays were employed to explore LLGL2 expression in human HCC samples and cell lines. Moreover, the clinical value of LLGL2 was investigated in 156 HCC patients. Furthermore, the role as well as the molecular mechanism of LLGL2 in the progression of HCC was explored through a series of in vitro and in vivo experiments.ResultsLLGL2 was up-regulated in HCC tissues, which was related with certain clinicopathological features including tumor number, vascular invasion as well as advanced stage. High expression of LLGL2 predicted poor prognosis after hepatectomy. LLGL2 promoted HCC cells proliferation, migration and invasion through PI3K/ATK signaling by promoting calcium ion influx.ConclusionOur study identified that LLGL2 is a tumor promoter in HCC for the first time, which could potentially be utilized as a new biomarker and a therapeutic target for HCC.

Postpancreatectomy haemorrhage (PPH) is a rare and life-threatening complication that can occur after pancreaticoduodenectomy (PD). Recently, radiological intervention has become a first-line approach for the diagnosis and treatment of late PPH in haemodynamically stable patients. Surgical intervention should be performed in haemodynamically unstable patients. We report the case of a 54-year-old man who underwent PD for ampullary carcinoma. On postoperative day (POD) 20, he developed a late PPH in the context of pancreatic fistula that was accompanied by hypotension and tachycardia. Therefore, emergency relaparotomy was performed, but the bleeding site was not detected due to severe adhesions in the surgical field. Thus, urgent angiography was performed immediately, and active bleeding was detected from the distal part of the proper hepatic artery. Coil embolisation of the proper hepatic artery trunk was successfully performed. No intrahepatic abscess or liver failure was subsequently observed, and the patient left our hospital on POD 27. This case shows that radiological intervention is a first choice for the diagnosis and treatment of haemodynamically stable late PPH and that it also might still be a first choice and also be safer and more effective than surgical intervention even with unstable haemodynamics.

Aim: The study aimed to investigate the clinical significance of preoperative alpha-fetoprotein (AFP) and gamma-glutamyl transferase (GGT) (A-G score) on hepatocellular carcinoma (HCC) patients.Methods: A total of 474 solitary HCC patients were included. Survival analysis was evaluated by Kaplan-Meier method. Prognostic factors were analyzed in a multivariate model. The comparison of the predictive value of AFP, GGT, and A-G score was performed by receiver operating characteristic curve (ROC) analysis and decision curve analysis (DCA).Results: Of the 474 patients, 137(28.9%), 241(50.8%), and 96(20.3%) patients were assigned to A-G score 0, 1, and 2, respectively. In multivariate analysis, A-G score, tumor size, microvascular invasion, tumor differentiation, satellite lesion, and state of HBV infection were independently predictive factors for RFS of solitary HCC patients. The A-G score could significantly stratify solitary HCC patients with a distinguished prognosis. The 1-, 3-, and 5-year RFS and OS among patients with A-G score 1 was better than that of patients with A-G score 2 and worse than that of patients with A-G score 0(all p < 0.05). Based on the result from the ROC analysis and DCA analysis, the A-G score appeared to be superior to either AFP or GGT alone in the prediction of prognosis of solitary HCC patients. In the subgroup analysis, the A-G score could accurately predict the prognosis of solitary HCC patients without MVI or with liver cirrhosis.Conclusions: Preoperative A-G score could effectively and simply predict prognosis of solitary HCC patients after hepatectomy, especially for those with non-MVI solitary HCC or those with liver cirrhosis.

Abstract Background The role of histone deacetylases 6 (HDAC6) has been elucidated in various neurodegenerative diseases. However, the effect of HDAC6 on retinal degenerative processes remains unknown. The aim of this study was to elucidate the potential role of HDAC6 in the retinal ischaemia and reperfusion (I/R) injury model. Methods The retinal pathological lesion was evaluated by haematoxylin and eosin (H&E) staining. HDAC expression or activity was detected by immunohistochemistry, Western blotting assays or colorimetric assays. The expression of apoptotic- and autophagic- related proteins were quantified by Western blotting and RT-PCR. The expression of peroxiredoxin 2 (Prx2) was determined by RT-PCR and ELISA. The levels of acetylated α-tubulin and acetylated histone 3 in the retina were assayed by Western blotting. Results We found that I/R-induced reduction of the retinal thickness was ameliorated, and the survival of RGCs was increased by the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) as well as by tubacin (an HDAC6 selective inhibitor). The decreased expression of THY (thymus cell antigen) in the I/R-induced retinas was also reversed by TSA and tubacin. Elevated HDAC6 expression and activity in the retina from I/R injury were significantly inhibited by tubacin, which also attenuated I/R-mediated apoptosis by decreasing TUNEL-positive RGCs and Bax expression and increasing Bcl-2 expression. Additionally, tubacin increased the expression of autophagy-related gene Beclin 1 and microtubule-associated protein 1 light chain 3B (LC3B) and the levels of Prx2. Furthermore, the protective effect of tubacin was associated with acetylated α-tubulin and was independent of acetylated histone 3. Conclusions Our findings suggest that tubacin exhibits neuroprotective effects after I/R retinal injury, and HDAC6 may be a potential therapeutic target for the retinal neurodegenerative disease of glaucoma.

Abstract Background Microvascular invasion (MVI) is well established as a negative prognostic factor for hepatocelluar carcinoma (HCC). However, its prognostic value in different subgroups of Barcelona Clinical Liver Cancer (BCLC) stages remains to be elucidated. Methods Four hundred fifty-eight MVI-negative and 204 MVI-positive patients who underwent hepatectomy were retrospectively analyzed. After propensity score matching (PSM) analysis, 187 pairs of matched patients were generated. Long-term survival was compared by the Kaplan–Meier method. Results Patients with MVI commonly had more advanced tumors. All the patients with MVI had significantly worse survival rate compared to the patients without MVI before and after PSM(p

Aim. The objective of this study was to evaluate short- and long-term survival after surgical treatment between young and older hepatocellular carcinoma (HCC) patients beyond the Milan criteria.Material and methods. One hundred fifty-seven HCC patients (≤ 55 years old) were categorized into group A, and one hundred fifty-eight HCC patients (> 55 years old) were categorized into group B. Postoperative complications and overall survival were retrospectively analyzed.Results. Older HCC patients had a higher rate of delayed extubation after surgery and suffered more complications after surgery, especially major complications. Intraoperative blood transfusion, liver fibrosis/cirrhosis and delayed extubation were risk factors related to postoperative complications. Microvascular invasion (MVI), tumor diameter, postoperative alpha-fetoprotein and the presence of satellites were independent risk factors for long-term survival. Young patients had more advanced tumors. Overall survival rates at 1, 3 and 5-years were 78.1%, 45.1% and 27.4% for young patients, respectively, and 86.5%, 57.5% and 42.4% for older patients, respectively (p = 0.007).Conclusion. The category A group had poorer tumor characteristics and worse prognoses than the category B group.

Background/AimsSolitary hepatocellular carcinoma (HCC) is a subgroup of HCCs. We aimed to establish nomograms for predicting the survival of solitary HCC patients after hepatectomy.Methods : A total of 538 solitary HCC patients were randomly classified into training and validation sets. A Cox model was used to identify predictors of overall survival (OS) in the training set. A nomogram was generated based on these predictors and was validated using the validation set.Results : Tumor size, microvascular invasion, and major vascular invasion were significantly associated with OS in the training set. Nomograms were developed based on these predictors in the multivariate analysis. The C-index was 0.75 for the OS nomogram and 0.72 for the recurrence-free survival nomogram. Compared to the index of conventional staging systems for predicting survival (0.71 for Barcelona Clinic Liver Cancer, 0.66 for the seventh American Joint Committee on Cancer, 0.68 for Cancer of the Liver Italian Program, and 0.70 for Hong Kong Liver Cancer), the index of the OS nomogram was significantly higher. Moreover, the calibration curve fitted well between the predicted and observed survival rate. Similarly, in the validation set, the nomogram discrimination was superior to those of the four staging systems (p

Aim: As high gamma-glutamyltransferase level or low albumin had negative impacts on the prognosis of hepatocellular carcinoma (HCC), the prognostic role of albumin to gamma-glutamyltransferase ratio (AGR) in HCC patients after hepatectomy remains unclear.Methods: Between January 2007 and December 2015, 1143 HCC patients after hepatectomy were reviewed from a prospectively maintained database in West China Hospital. All qualified patients (n = 959) were classified as training set (year 2007–2012, n = 480) and validation set (year 2012–2017, n = 479). A time-dependent receiver operating characteristic (ROC) curve analysis was performed to evaluate the performance.Result: AGR = 0.5 was identified as the best cut-off point to predict recurrence free survival (RFS) and overall survival (OS) in the training set. Low AGR was related to poor tumor characteristics and high systemic inflammation. Based on the multivariate analysis, high AGR was an independent predictor for better RFS and OS with an hazard ratio of 0.696 and 0.673. The high AGR group had better RFS and OS than the low AGR group in the training set as well as the validation set. The AGR-based score (AGR-PLR) could stratify HCC patients into three subgroups with different prognosis in the training and validation set. Patients with score 1 had a worse prognosis than those with AGR-PLR score 0, but better than those with AGR-PLR score 2. The predictive accuracy of the AGR-PLR score appeared superior to that of the AGR or PLR alone.Conclusions: we firstly reported that AGR ≤ 0.5 was an independently prognostic factor in HCC after hepatectomy. The AGR-PLR score could further improve the discriminatory ability of prognosis.