An aptamer-guided fluorescence polarisation platform for extracellular vesicle liquid biopsy.

The translation of discoveries on extracellular vesicle (EV) based cancer biomarkers to personalised precision oncology requires the development of robust, sensitive and specific assays that are amenable to adoption in the clinical laboratory. Whilst a variety of elegant approaches for EV liquid biopsy have been developed, most of them remain as research prototypes due to the requirement of a high level of microfabrication and/or sophisticated instruments. Hence, this study is set to develop a simple DNA aptamer-enabled and fluorescence polarisation-based homogenous assay that eliminates the need to separate unbound detection ligands from the bound species for EV detection. High specificity is achieved by immobilising EVs with one set of antibodies and subsequently detecting them with a DNA aptamer targeting a distinct EV biomarker. This two-pronged strategy ensures the removal of most, if not all, non-EV substances in the input biofluids, including soluble proteins, protein aggregates or non-vesicular particles, prior to quantifying biomarker-positive EVs. A limit of detection of 5.0 × 106 EVs/mL was achieved with a linear quantification range of 5.0 × 108 to 2.0 × 1010 EVs/mL. Facilitated by a multiple parametric analysis strategy, this aptamer-guided fluorescence polarisation assay was capable of distinguishing EVs from three different types of solid cancer cells based on quantitative differences in the levels of the same sets of biomarkers on EVs. Given the simplicity of the method and its ease of implementation in automated clinical biochemistry analysers, this assay could be exploited for future EV-based continuous and real-time monitoring of the emergence of new macro- or micro-metastasis, cancer progression as well as the response to treatment throughout different stages of cancer management in the clinic.

Regulatory effect of Yinchenhao decoction on bile acid metabolism to improve the inflammatory microenvironment of hepatocellular carcinoma in mice.

Hepatocellular carcinoma (HCC) is a malignant tumor with extremely high mortality. The tumor microenvironment is the "soil" of its occurrence and development, and the inflammatory microenvironment is an important part of the "soil". Bile acid is closely related to the occurrence of HCC. Bile acid metabolism disorder is not only directly involved in the occurrence and development of HCC but also affects the inflammatory microenvironment of HCC. Yinchenhao decoction, a traditional Chinese medicine formula, can regulate bile acid metabolism and may affect the inflammatory microenvironment of HCC. To determine the effect of Yinchenhao decoction on bile acid metabolism in mice with HCC and to explore the possible mechanism by which Yinchenhao decoction improves the inflammatory microenvironment of HCC by regulating bile acid metabolism, we established mice model of orthotopic transplantation of hepatocellular carcinoma. These mice were treated with three doses of Yinchenhao decoction, then liver samples were collected and tested. Yinchenhao decoction can regulate the disorder of bile acid metabolism in liver cancer mice. Besides, it can improve inflammatory reactions, reduce hepatocyte degeneration and necrosis, and even reduce liver weight and the liver index. Taurochenodeoxycholic acid, hyodeoxycholic acid, and taurohyodeoxycholic acid are important molecules in the regulation of the liver inflammatory microenvironment, laying a foundation for the regulation of the liver tumor inflammatory microenvironment based on bile acids. Yinchenhao decoction may improve the inflammatory microenvironment of mice with HCC by ameliorating hepatic bile acid metabolism.

Association of the sarcopenia index with cognitive impairment in a middle-aged to older patients with acute ischemic stroke or transient ischemic attack: A multicenter cohort study.

OBJECTIVES: The sarcopenia (SI) index, defined as the serum creatinine to cystatin C ratio, is considered a predictor of poor muscle health and malnutrition, which is related to major adverse cardiovascular events. However, the effect of the SI index on cognitive function in stroke patients remains unknown. In this study, we aimed to examine the association between the SI and longitudinal cognitive impairment in patients with acute ischemic stroke or transient ischemic attack. RESEARCH DESIGN AND METHODS: Participants who met the inclusion criteria in this national, multicenter, prospective cohort study were enrolled from the Impairment of Cognition and Sleep (ICONS) study of the China National Stroke Registry-3 (CNSR-3). They were categorized into four groups according to the quartile of the SI index. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale. Multivariable-adjusted logistic regression models were performed to evaluate the association between the SI index and post-stroke cognitive impairment (PSCI) at the 3-month follow-up. Moreover, discrimination tests were used to evaluate the incremental predictive value of the SI index beyond the potential risk factors. Furthermore, we performed subgroup analyses to test interactions. RESULTS: Among the enrolled participants, the lower the SI index was, the worse the cognitive performance. At the 3-month follow-up, participants in the lowest SI quartile group exhibited a 42% increase in the risk of cognitive impairment relative to the highest quartile group [OR 0.58 (95% CI 0.37-0.90)]. Moreover, after applying the discrimination test, adding the SI index into the potential risk factors resulted in a slight improvement in predicting the risk of cognitive impairment [NRI 14% (P = 0.01)]. CONCLUSION: This study demonstrated that a lower sarcopenia index was positively associated with a higher prevalence of PSCI. Monitoring the SI index in stroke patients and early identification and treatment of individuals with low SI level may be helpful to reduce the risk of cognitive impairment.

The M2 Macrophages Derived Migrasomes From the Surface of Titania Nanotubes Array as a New Concept for Enhancing Osteogenesis.

As newly discovered substrate anchored extracellular vesicles, migrasomes (Migs) may bring a new opportunity for manipulating target cells bioactivities. In this study, the M2 macrophages derived Migs are obtained by titania nanotubes surface (NTs). Due to the benefits of nanostructuring, the NTs surface is not only able to induce RAW264.7 for M2 polarization but also to generate more Migs formation, which can be internalized by following seeded mesenchymal stem cells (MSCs). Then, the NTs surface induced Migs are collected by density-gradient centrifugation for MSCs treatment. As indicated by immunofluorescence staining, alkaline phosphatase activity, and alizarin red staining, the osteogenic differentiation capacity of MSCs is significantly enhanced by Migs treatment, in line with the dosage. By RNA-sequence analysis, the enhancement of osteogenic differentiation is correlated with PI3K-AKT pathway activation that may originate from the M2 polarization state of donor cells. Finally, the Migs are coated onto Ti surface for therapeutic application. Both the in vitro and in vivo analysis reveal that the Migs coated Ti implant shows significant enhancement of osteogenesis. In conclusion, this study suggests that the nanosurface may be a favorable platform for Migs production, which may bring a new concept for tissue regeneration.

The clinical characteristics, gene mutations and outcomes of myelodysplastic syndromes with diabetes mellitus.

PURPOSE: Diabetes mellitus (DM) is the second most common comorbidity in myelodysplastic syndromes (MDS). The purpose of the study was to investigate the clinical characteristics of MDS patients with DM. METHODS: A retrospective analysis was performed on the clinical data of 890 MDS patients with or without DM. Clinical data, including genetic changes, overall survival (OS), leukemia-free survival (LFS) and infection, were analyzed. RESULTS: Among 890 patients, 184 (20.7%) had DM. TET2 and SF3B1 mutations occurred more frequently in the DM group than those in the non-DM group (p = 0.0092 and p = 0.0004, respectively). Besides, DM was an independent risk factor for infection (HR 2.135 CI 1.451-3.110, p = 0.000) in MDS. Compared to non-DM patients, MDS patients with DM had poor OS and LFS (p = 0.0002 and p = 0.0017, respectively), especially in the lower-risk group. While in multivariate analysis, DM did not retain its prognostic significance and the prognostic significance of infection was maintained (HR 2.488 CI 1.749-3.538, p = 0.000). CONCLUSIONS: MDS patients with DM have an inferior prognosis which may due to higher infection incidence, with TET2 and SF3B1 mutations being more frequent in those cases.

Guanylate binding protein 4 shapes an inflamed tumor microenvironment and identifies immuno-hot tumors.

PURPOSE: Guanylate binding protein 4 (GBP4) is induced by interferons and various cytokines and has been recognized as functionally relevant in numerous types of human cancers. While the role of GBP4 in cancer has been preliminarily summarized, its correlation with antitumor immunity remains unclear and requires further research. METHODS: First, a comprehensive pan-cancer analysis was conducted, focusing on GBP4's expression patterns and immunological functions. Subsequently, we explored the correlations between GBP4 and immunological features within the tumor microenvironment (TME) in non-small cell lung cancer (NSCLC) patients. Additionally, we examined the relationships between GBP4 and emerging immunobiomarkers, such as N6-methyladenosine (m6A) genes. Moreover, we assessed the utility of GBP4 in predicting the clinical characteristics and treatment responses of patients with NSCLC. RESULTS: Pan-cancer analysis revealed that GBP4 plays a positive role in most cancer types via the majority of immunomodulators. Furthermore, GBP4 demonstrated positive associations with immunomodulatory factors, tumor-infiltrating immune cells (TIICs) and inhibitory immune checkpoints. Remarkably, the expression of GBP4 was found to be a predictor of significantly enhanced responsiveness to anti-EGFR therapy and immunotherapy. CONCLUSIONS: GBP4 expression profiles offer a promising avenue for identifying highly immunogenic tumors across a wide spectrum of cancers. GBP4 holds potential as a robust pan-cancer biomarker for assessing the immunological characteristics of tumors, with particular relevance to its ability to predict therapeutic responses, notably in the context of anti-EGFR therapy and immunotherapy.

Association between CT-based adipose variables, preoperative blood biochemical indicators and pathological T stage of clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is corelated with tumor-associated material (TAM), coagulation system and adipocyte tissue, but the relationships between them have been inconsistent. Our study aimed to explore the cut-off intervals of variables that are non-linearly related to ccRCC pathological T stage for providing clues to understand these discrepancies, and to effectively preoperative risk stratification. Methods: This retrospective analysis included 218 ccRCC patients with a clear pathological T stage between January 1st, 2014, and November 30th, 2021. The patients were categorized into two cohorts based on their pathological T stage: low T stage (T1 and T2) and high T stage (T3 and T4). Abdominal and perirenal fat variables were measured based on preoperative CT images. Blood biochemical indexes from the last time before surgery were also collected. The generalized sum model was used to identify cut-off intervals for nonlinear variables. Results: In specific intervals, fibrinogen levels (FIB) (2.63-4.06 g/L) and platelet (PLT) counts (>200.34 × 109/L) were significantly positively correlated with T stage, while PLT counts (<200.34 × 109/L) were significantly negatively correlated with T stage. Additionally, tumor-associated material exhibited varying degrees of positive correlation with T stage at different cut-off intervals (cut-off value: 90.556 U/mL). Conclusion: Preoperative PLT, FIB and TAM are nonlinearly related to pathological T stage. This study is the first to provide specific cut-off intervals for preoperative variables that are nonlinearly related to ccRCC T stage. These intervals can aid in the risk stratification of ccRCC patients before surgery, allowing for developing a more personalized treatment planning.

Lentinan has a beneficial effect on cognitive deficits induced by chronic Toxoplasma gondii infection in mice.

BACKGROUND: Toxoplasma gondii (T. gondii) is increasingly considered a risk factor for neurodegenerative diseases. However, there is only limited information on the development of drugs for T. gondii infection. Lentinan from Lentinula edodes is a bioactive ingredient with the potential to enhance anti-infective immunity. The present study aimed to investigate the neuroprotective effect of lentinan on T. gondii-associated cognitive deficits in mice. METHODS: A chronic T. gondii infection mouse model was established by administering 10 cysts of T. gondii by gavage. Lentinan was intraperitoneally administered 2 weeks before infection. Behavioral tests, RNA sequencing, immunofluorescence, transmission electron microscopy and Golgi-Cox staining were performed to assess the effect of lentinan on cognitive deficits and neuropathology in vivo. In vitro, the direct and indirect effects of lentinan on the proliferation of T. gondii tachyzoites were evaluated in the absence and presence of BV-2 cells, respectively. RESULTS: Lentinan prevented T. gondii-induced cognitive deficits and altered the transcriptome profile of genes related to neuroinflammation, microglial activation, synaptic function, neural development and cognitive behavior in the hippocampus of infected mice. Moreover, lentinan reduced the infection-induced accumulation of microglia and downregulated the mRNA expression of proinflammatory cytokines. In addition, the neurite and synaptic ultrastructural damage in the hippocampal CA1 region due to infection was ameliorated by lentinan administration. Lentinan decreased the cyst burden in the brains of infected mice, which was correlated with behavioral performance. In line with this finding, lentinan could significantly inhibit the proliferation of T. gondii tachyzoites in the microglial cell line BV2, although lentinan had no direct inhibitory effect on parasite growth. CONCLUSIONS: Lentinan prevents cognitive deficits via the improvement of neurite impairment and synaptic loss induced by T. gondii infection, which may be associated with decreased cyst burden in the brain. Overall, our findings indicate that lentinan can ameliorate T. gondii-related neurodegenerative diseases.

ROBO1 deficiency impairs HSPC homeostasis and erythropoiesis via CDC42 and predicts poor prognosis in MDS.

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic neoplasms originating from hematopoietic stem progenitor cells (HSPCs). We previously identified frequent roundabout guidance receptor 1 (ROBO1) mutations in patients with MDS, while the exact role of ROBO1 in hematopoiesis remains poorly delineated. Here, we report that ROBO1 deficiency confers MDS-like disease with anemia and multilineage dysplasia in mice and predicts poor prognosis in patients with MDS. More specifically, Robo1 deficiency impairs HSPC homeostasis and disrupts HSPC pool, especially the reduction of megakaryocyte erythroid progenitors, which causes a blockage in the early stages of erythropoiesis in mice. Mechanistically, transcriptional profiling indicates that Cdc42, a member of the Rho-guanosine triphosphatase family, acts as a downstream target gene for Robo1 in HSPCs. Overexpression of Cdc42 partially restores the self-renewal and erythropoiesis of HSPCs in Robo1-deficient mice. Collectively, our result implicates the essential role of ROBO1 in maintaining HSPC homeostasis and erythropoiesis via CDC42.

Prediction of Fuhrman nuclear grade for clear cell renal carcinoma by a multi-information fusion model that incorporates CT-based features of tumor and serum tumor associated material.

PURPOSE: Prediction of Fuhrman nuclear grade is crucial for making informed herapeutic decisions in clear cell renal cell carcinoma (ccRCC). The current study aimed to develop a multi-information fusion model utilizing computed tomography (CT)-based features of tumors and preoperative biochemical parameters to predict the Fuhrman nuclear grade of ccRCC in a non-invasive manner. METHODS: 218 ccRCC patients confirmed by histopathology were retrospectively analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent predictors and establish a model for predicting the Fuhrman grade in ccRCC. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration, the 10-fold cross-validation method, bootstrapping, the Hosmer-Lemeshow test, and decision curve analysis (DCA). RESULTS: R.E.N.A.L. Nephrometry Score (RNS) and serum tumor associated material (TAM) were identified as independent predictors for Fuhrman grade of ccRCC through multivariate logistic regression. The areas under the ROC curve (AUC) for the multi-information fusion model composed of the above two factors was 0.810, higher than that of the RNS (AUC 0.694) or TAM (AUC 0.764) alone. The calibration curve and Hosmer-Lemeshow test showed the integrated model had a good fitting degree. The 10-fold cross-validation method (AUC 0.806) and bootstrap test (AUC 0.811) showed the good stability of the model. DCA demonstrated that the model had superior clinical utility. CONCLUSION: A multi-information fusion model based on CT features of tumor and routine biochemical indicators, can predict the Fuhrman grade of ccRCC using a non-invasive approach. This model holds promise for assisting clinicians in devising personalized management strategies.

H19/Mir-130b-3p/Cyp4a14 potentiate the effect of praziquantel on liver in the treatment of Schistosoma japonicum infection.

BACKGROUND: Schistosomiasis is a prevalent infectious disease caused by the parasitic trematodes of the genus Schistosoma. Praziquantel (PZQ), a safe and affordable drug, is the recommended oral treatment for schistosomiasis. The main pathologic manifestation of schistosomiasis is liver injury. However, the role and interactions of various RNA molecules in the effect of PZQ on the liver after S. japonicum infection have not been elucidated. RESULTS: In this study, C57BL/6 mice were randomly divided into the control group, infection group, and PZQ treatment group. Total RNA was extracted from the livers of the mice. High-throughput whole transcriptome sequencing was performed to detect the RNA expression profiles in the three groups. A co-expression gene-interaction network was established based on the significant differentially expressed genes in the PZQ treatment group; messenger RNA (mRNA) Cyp4a14 was identified as a critical hub gene. Furthermore, competitive endogenous RNA networks were constructed by predicting the specific binding relations between mRNA and long noncoding (lnc) RNA and between lncRNA and microRNA (miRNA) of Cyp4a14, suggesting the involvement of the H19/miR-130b-3p/Cyp4a14 regulatory axis. Dual luciferase reporter assay result proved the specific binding of miR-130b-3p with Cyp4a14 3'UTR. CONCLUSIONS: Our findings indicate the involvement of the H19/miR-130b-3p/Cyp4a14 axis in the effect of PZQ on the liver after S. japonicum infection. Moreover, the expression of mRNA Cyp4a14 could be regulated by the bonding of miR-130b-3p with 3'UTR of Cyp4a14. The findings of this study could provide a novel perspective to understand the host response to PZQ against S. japonicum in the future.

Association of mechanical power during one-lung ventilation and post-operative pulmonary complications among patients undergoing lobectomy: a protocol for a prospective cohort study.

The association of intra-operative mechanical power (MP) with post-operative pulmonary complications (PPCs) has been described before, but it is uncertain whether the potential inherent bias can limit the use of this parameter, particularly in the context of one-lung ventilation. This single-center study aims to investigate the effect of MP during one-lung ventilation (OLV), and the risks of PPCs in patients undergoing thoracoscopic lobectomy. This prospective observational study is being conducted in an academic tertiary hospital in mainland China. Participants diagnosed with lung cancer, and aged 50 to 80 years are eligible. Video-assisted thoracoscopic surgery (VATS) lobectomy is performed for all patients. The primary outcome is the occurrence of PPCs over 5 consecutive days after the surgery, or until discharge from the hospital. Secondary outcomes include the composite conditions of PPCs, in-hospital stay, systematic inflammation tested by blood samples, and changes in aeration compartments in the ventilated lung as assessed by CT scans. We aim to evaluate the association of mean MP and the temporal patterns in the trend of MP during OLV with the occurrence of PPCs. A total of 120 patients will be enrolled in this study. The study protocol has received approval from the Ethics Committee of the affiliated hospital of Southwest Medical University, China (Reference number: KY2022162). The findings will be made available to the funder and researchers via scientific conferences and peer-reviewed publications. This controlled trial was approved by the Ethics Committee of Southwest Medical University(ChiCTR2200062173), and registered in the Chinese Clinical Trial Register website ( http://www.chictr.org.cn/edit.aspx?pid=172533&htm=4 , ChiCTR2200062173). A written consent was obtained from each patient.

The phosphotransferase system gene ptsH affects persister formation in Klebsiella pneumoniae by regulating cyclic adenosine monophosphate levels.

Klebsiella pneumoniae is one of the most common opportunistic pathogens causing hospital- and community-acquired infections. Antibiotic resistance in K. pneumoniae has emerged as a major clinical and public health threat. Persisters are specific antibiotic-tolerant bacterial cells. Studies on the mechanism underlying their formation mechanism and growth status are scarce. Therefore, it is urgent to explore the key genes and signalling pathways involved in the formation and recovery process of K. pneumoniae persisters to enhance the understanding and develop relevant treatment strategies. In this study, we treated K. pneumoniae with a lethal concentration of levofloxacin. It resulted in a distinct plateau of surviving levofloxacin-tolerant persisters. Subsequently, we obtained bacterial samples at five different time points during the formation and recovery of K. pneumoniae persisters to perform transcriptome analysis. ptsH gene was observed to be upregulated during the formation of persisters, and down-regulated during the recovery of the persisters. Further, we used CRISPR-Cas9 to construct ΔptsH, the ptsH-knockout K. pneumoniae strain, and to investigate the effect of ptsH on the persister formation. We observed that ptsH can promote the formation of persisters, reduce accumulation of reactive oxygen species, and enhance antioxidant capacity by reducing cyclic adenosine monophosphate (cAMP) levels. To the best of our knowledge, this is the first study to report that ptsH plays a vital role in forming K. pneumoniae persisters. This study provided important insights to further explore the mechanism underlying the formation of K. pneumoniae persisters and provided a potential target for treating infection with K. pneumoniae persisters.

Enhanced cadmium phytoextraction efficiency of ryegrass (Lolium perenne L.) by porous media immobilized Enterobacter sp. TY-1.

Although studies on immobilized microorganisms have been conducted, their performance remains unclear for enhancing plants to remediate cadmium (Cd)-contaminated soil. In this study, a Cd-resistant strain TY-1 with good plant growth promotion traits was immobilized by biochar (BC) or oyster shell (OS) power to strengthen ryegrass to remediate Cd-contaminated soil. SEM-EDS combined with FTIR showed that TY-1 could tolerate Cd toxicity by surface precipitation, and functional groups such as hydroxyl and carbonyl groups might be involved. In the biocomposite treatments, soil pH increased, and the activity of fertility-related enzymes such as dehydrogenase increased by 109.01%-128.01%. The relative abundance of genus Saccharimonadales decreased from 7.97% to 3.35% in BS-TY and 2.61% in OS-TY, respectively. Thus, a suitable environment for ryegrass growth was created. The fresh weight, dry weight, plant height and Cd accumulation of ryegrass in TY treatment increased by 122.92%, 114.81%, 42.08% and 8.05%, respectively, compared to the control. Cd concentration in ryegrass was further increased in BC-TY and OS-TY by 24.14% and 40.23%, respectively. The improvement in soil microcosm and plant biomass forms an ongoing virtuous cycle, demonstrating that using carrier materials to improve the efficiency of microbial-assisted phytoremediation is realistic and feasible.

Language dysfunction correlates with cognitive impairments in older adults without dementia mediated by amyloid pathology.

Background: Previous studies have explored the application of non-invasive biomarkers of language dysfunction for the early detection of Alzheimer's disease (AD). However, language dysfunction over time may be quite heterogeneous within different diagnostic groups. Method: Patient demographics and clinical data were retrieved from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database for the participants without dementia who had measures of cerebrospinal fluid (CSF) biomarkers and language dysfunction. We analyzed the effect of longitudinal neuropathological and clinical correlates in the pathological process of semantic fluency and confrontation naming. The mediation effects of AD biomarkers were also explored by the mediation analysis. Result: There were 272 subjects without dementia included in this analysis. Higher rates of decline in semantic fluency and confrontation naming were associated with a higher risk of progression to MCI or AD, and a greater decline in cognitive abilities. Moreover, the rate of change in semantic fluency was significantly associated with Aß deposition, while confrontation naming was significantly associated with both amyloidosis and tau burden. Mediation analyses revealed that both confrontation naming and semantic fluency were partially mediated by the Aß aggregation. Conclusion: In conclusion, the changes in language dysfunction may partly stem from the Aß deposition, while confrontation naming can also partly originate from the increase in tau burden. Therefore, this study sheds light on how language dysfunction is partly constitutive of mild cognitive impairment and dementia and therefore is an important clinical predictor.

Evaluation of the up-to-7 criterion for determining the treatment of hepatocellular carcinoma in Barcelona Clinic Liver Cancer stage B: a single-center retrospective cohort study.

Background: At present, there are still disputes on the treatment of surgery for patients with stage B hepatocellular carcinoma (HCC). This study sought to investigate whether the up-to-7 criterion could be used to decide the treatment for HCC in Barcelona Clinic Liver Cancer stage B (BCLC-B). Methods: We analyzed 340 patients with HCC in BCLC-B who treated with hepatectomy or transcatheter arterial chemoembolization (TACE). Of the 285 HCC patients who underwent hepatectomy, 108 met the up-to-7 criterion and 177 exceeded it. All 55 patients in the TACE group met the up-to-7 criterion. We obtained the tumor status of the patients through inpatient medical records, outpatient medical records, and telephone follow-up of the hospital. We compared overall survival (OS) and progression-free survival (PFS) were compared between patients who met the up-to-7 criterion and who underwent either hepatectomy or TACE. OS and recurrence time were also compared between the patients who were treated with hepatectomy and who either met or exceeded the up-to-7 criterion. Across BCLC-B patients, we compared the OS of patients after surgical treatment between subgroups stratified by tumor number and diameter. Results: Patients who met the up-to-7 criterion had significantly higher OS rates after hepatectomy than TACE (P<0.001). However, the 2 groups did not differ in terms of PFS (P=0.758). Among the patients treated by hepatectomy, the OS rates were significantly higher in patients who met the up-to-7 criterion than in those who exceeded it (P=0.001). The recurrence rates did not differ between patients who met or exceeded the criterion (P=0.662). OS was significantly higher in patients with ≤3 tumors than those with >3 tumors (P=0.001). When we stratified patients with ≤3 tumors based in whether they met or exceeded the up-to-8 to up-to-15 criterion, OS was significantly better among those who met the criterion in all cases. Conclusions: Hepatectomy appears to be associated with better survival than TACE in patients with BCLC-B HCC who meet the up-to-7 criterion, but this criterion is not a strict indication for deciding whether to treat patients with BCLC-B surgically. Tumor number strongly affects the prognosis of BCLC-B patients after hepatectomy.