Background: Time-restricted feeding, also known as intermittent fasting, can confer various beneficial effects, especially protecting against obesity, and related metabolic disorders, but little is known about the underlying mechanisms. Therefore, the present study aims to investigate the effects of time-restricted feeding on the circadian rhythm of gut microbiota and hepatic metabolism.Methods: Eight-week-old male Kunming mice received either a normal diet ad libitum, a high-fat diet ad libitum, or a high-fat diet restricted to an 8-h temporal window per day for an experimental period of 8 weeks. Weight gain and calorie intake were measured weekly. Serum metabolites, hepatic sections and lipid metabolites, gut microbiota, and the hepatic expression of Per1, Cry1, Bmal1, SIRT1, SREBP, and PPARα were measured at the end of the experimental period. The composition of gut microbiota and the expression of hepatic genes were compared between four timepoints.Results: Mice that received a time-restricted high-fat diet had less weight gain, milder liver steatosis, and lower hepatic levels of triglycerides than mice that received a high-fat diet ad libitum (p < 0.05). The numbers of Bacteroidetes and Firmicutes differed between mice that received a time-restricted high-fat diet and mice that received a high-fat diet ad libitum (p < 0.05). Mice fed a time-restricted high-fat diet showed distinct circadian rhythms of hepatic expression of SIRT1, SREBP, and PPARα compared with mice fed a normal diet ad libitum, as well as the circadian rhythm of the abundance of Bacteroidetes and Firmicutes.Conclusions: Time-restricted feeding is associated with better metabolic conditions, perhaps owing to alterations in gut microbiota and the circadian pattern of molecules related to hepatic lipid metabolism, which were first to report.

Radiofrequency ablation (RFA) is recommended as a first-line therapy for small hepatocellular carcinoma (HCC). Tumor location is a potential factor influencing the procedure of RFA. To compare oncologic outcomes of RFA for different tumor locations, this retrospective study enrolled 194 patients with small HCC who had undertaken RFA. The HCC nodules were classified as peri-hepatic-vein (pHV) or non-pHV, peri-portal-vein (pPV) or non-pPV, and subcapsular or non-subcapsular HCC. The regional recurrence-free survival (rRFS), overall survival (OS), recurrence-free survival (recurrence in any location, RFS) and distant recurrence-free survival (dRFS) were compared. Operation failures were recorded in five pPV HCC patients, which was more frequent than in non-pPV HCC patients (p = 0.041). The 1-, 3-, and 5-year rRFS was 68.7%, 53.7%, and 53.7% for pHV patients and 85.1%, 76.1%, and 71.9% for non-pHV patients, respectively (p = 0.012). After propensity score matching, the 1-, 3-, and 5-year rRFS was still worse than that of non-pHV patients (p = 0.013). The OS, RFS, and dRFS were not significantly different between groups. Conclusions: A pHV location was a risk factor for the regional recurrence after RFA in small HCC patients. The tumor location may not influence OS, RFS, and dRFS. Additionally, a pPV location was a potential high-risk factor for incomplete ablation.

Introduction: To investigate the prognostic significance of liver tumor markers, the hemoglobin, albumin, lymphocyte, and platelet (HALP) score; neutrophil-to-lymphocyte ratio (NLR); and platelet-to-lymphocyte ratio (PLR), for predicting the specific site of recurrence or metastasis after surgery in patients with intrahepatic cholangiocarcinoma (ICC). Methods: In total, 162 patients with pathologically proven ICC who underwent curative surgery at Sun Yat-sen University Cancer Center between April 2016 and April 2020 were analyzed. Clinicopathological characteristics were collected retrospectively. The Kaplan–Meier method was used to analyze the overall survival (OS) and recurrence-free survival (RFS). Significant clinical factors were examined by univariate analysis and multivariate analysis and analyzed by receiver operating characteristic (ROC) curve analysis. Results: The cutoff values for the HALP score, NLR, and PLR were determined to be 43.63, 3.73, and 76.51, respectively, using the surv_cutpoint function of survminer using RFS as the target variable. In multivariate analysis, vascular invasion, pathology nerve tract invasion, and carbohydrate antigen 19-9 (CA19-9) levels were independent prognostic factors of OS, whereas the tumor number, pathology microvascular invasion, pathology differentiation, CA19-9 levels, and NLR were independent prognostic factors of RFS. For the whole recurrence analysis, the carcinoembryonic antigen (CEA) index exhibited the largest ROC curve area of all (AUC = 0.590), and the alpha-fetoprotein (AFP) index exhibited the smallest ROC curve area (AUC = 0.530). The HALP score exhibited the largest ROC curve area of all in predicting intrahepatic recurrence (AUC = 0.588), the NLR showed the best predictive value in predicting lymph node metastasis (AUC = 0.703), and the AUC of the CA19-9 index was the largest of all variables in predicting distant metastasis (AUC = 0.619). Conclusions: Our study showed that CA19-9, CEA, HALP score, and NLR are easily accessible, reliable, cost-effective indexes for predicting the specific site of recurrence or metastasis after surgery in ICC patients. Patients with high HALP scores and NLR have a higher risk of intrahepatic and lymph node metastasis recurrence.

Background: The Y-box-binding proteins (YBX) act as a multifunctional role in tumor progression, metastasis, drug resistance by regulating the transcription and translation process. Nevertheless, their functions in a pan-cancer setting remain unclear.Methods: This study examined the clinical features expression, prognostic value, mutations, along with methylation patterns of three genes from the YBX family (YBX1, YBX2, and YBX3) in 28 different types of cancer. Data used for analysis were obtained from Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. A novel YBXs score was created using the ssGSEA algorithm for the single sample gene set enrichment analysis. Additionally, we explored the YBXs score’s association with the tumor microenvironment (TME), response to various treatments, and drug resistance.Results: Our analysis revealed that YBX family genes contribute to tumor progression and are indicative of prognosis in diverse cancer types. We determined that the YBXs score correlates significantly with numerous malignant pathways in pan-cancer. Moreover, this score is also linked with multiple immune-related characteristics. The YBXs score proved to be an effective predictor for the efficacy of a range of treatments in various cancers, particularly immunotherapy. To summarize, the involvement of YBX family genes is vital in pan-cancer and exhibits a significant association with TME. An elevated YBXs score indicates an immune-activated TME and responsiveness to diverse therapies, highlighting its potential as a biomarker in individuals with tumors. Finally, experimental validations were conducted to explore that YBX2 might be a potential biomarker in liver cancer.Conclusion: The creation of YBXs score in our study offered new insights into further studies. Besides, YBX2 was found as a potential therapeutic target, significantly contributing to the improvement of HCC diagnosis and treatment strategies.

Purpose: Inflammatory response is related to tumor progression and patient survival. We aimed to clarify the prognostic value of the inflammation-based scores in intrahepatic cholangiocarcinoma (ICC) patients receiving anti-PD1 therapy. Patients and Methods: A total of 73 patients who received anti-PD-1 therapy from February 2019 to February 2021 were included in the study. Representative inflammation-based prognostic scores, including C-reactive protein (CRP), the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-CRP ratio (LCR), lymphocyte-to-monocyte ratio (LMR), systemic immune inflammation index (SII), CRP-to-albumin ratio (CAR), prognostic nutritional index (PNI), Glasgow Prognostic Score (GPS), and prognostic index (PI), were assessed for prediction accuracy using Kaplan–Meier survival curves and time-dependent receiver operating characteristic (ROC). All the ten inflammation-based prognostic scores were measured before receiving anti-PD1 therapy. Results: All the ten inflammation-based prognostic scores showed good discriminatory ability in terms of overall survival (OS) (all P < 0.01), the higher the score, the worse the prognosis, while the CRP score was a remarkable independent predictor for OS in multivariate analysis (hazard ratio, 6.032; confidence interval, 2.467– 14.752; P < 0.001). The area under the ROC curve at 6 months, 12 months, 18 months and 24 months consistently demonstrated that the predictive value of the CRP score was superior to other inflammation-based scores. Conclusion: Inflammation-based scores predict the efficacy of anti-PD-1 therapy in patients with ICC and CRP score superior to the other inflammation-based prognostic scores in terms of predictive ability.

INTRODUCTION: The global burden of metabolic diseases is increasing, but estimates of their impact on primary liver cancer are uncertain. We aimed to assess the global burden of primary liver cancer attributable to metabolic risk factors, including high body mass index (BMI) and high fasting plasma glucose (FPG) levels, between 1990 and 2021. METHODS: The total number and age-standardized rates of deaths and disability-adjusted life years (DALYs) from primary liver cancer attributable to each metabolic risk factor were extracted from the Global Burden of Disease Study 1990–2021. The metabolic burden trends of liver cancer across regions and countries by sociodemographic index (SDI) and sex were estimated. The annual percentage changes in age-standardized DALYs rate were also calculated. RESULTS: Globally, in 2021, primary liver cancer attributable to high BMI and/or high FPG was estimated to have caused 59,970 deaths (95% uncertainty interval [UI] 20,567–104,103) and 1,540,437 DALYs (95% UI 540,922–2,677,135). The age-standardized rates of death and DALYs were 0.70 (95% UI 0.24–1.21) and 17.64 (95% UI 6.19–30.65) per 100,000 person-years. A consistent global rise in liver cancer attributable to metabolic risks was observed from 1990 to 2021, with high BMI identified as the major contributing risk factor. The highest burden of deaths and DALYs of liver cancer consistently occurred in high SDI countries, while the fastest growth trends were observed in low-middle SDI countries. The burdens of high levels of BMI and FPG were higher in men than in women. DISCUSSION: Primary liver cancer attributable to high BMI and/or high FPG imposes an increasingly substantial clinical burden on global public health, particularly in high SDI countries. Rapid growth trends are also found in middle SDI countries.