Enhancing the Catalytic Activity of Laccase@Copper-Metal-Organic Framework Nanofractal Microspheres: Synergistic Contribution of the Mass Transfer and Electron Transfer Pathway.

Metal-organic frameworks (MOFs) are limited by small pores and buried active sites, and their enzyme-like catalytic activity is still very low. Herein, laccase was employed as the organic component to construct laccase@Cu3(BTC)2 nanofractal microspheres. During the preparation process, laccase adsorbed Cu2+ by electrostatic attractive interaction, then combined with Cu2+ by coordination interaction, and finally induced the in situ growth of H3BTC2 in multiple directions by electrostatic repulsion. Interestingly, electrostatic repulsion was tuned efficiently by adjusting the Cu2+ concentration to obtain laccase@Cu3(BTC)2 nanofractal microspheres (nanosheet microspheres, nanorod microspheres, and nanoneedle microspheres). Laccase@Cu3(BTC)2 nanorod microspheres exhibited the highest catalytic efficiency, which was 14-fold higher than that of smooth microspheres. The mechanism of the improvement of catalytic activity in the degradation of BPA was proposed for the first time. The enhanced catalytic activity depended on the adsorption effect of the nanorod framework and dual cycle synergistic catalysis of Cu+/Cu2+ active sites, which accelerated substrate diffusion and electron transfer. The catalytic mechanism of enzyme@MOF nanofractal microspheres not only deepens our understanding of enzyme and MOF synergistic catalysis but also provides new insights into the design of catalysts.

TLR3 activation enhances abscopal effect of radiotherapy in HCC by promoting tumor ferroptosis.

Radiotherapy (RT) has been reported to induce abscopal effect in advanced hepatocellular carcinoma (HCC), but such phenomenon was only observed in sporadic cases. Here, we demonstrated that subcutaneous administration of Toll-like receptor 3 (TLR3) agonist poly(I:C) could strengthen the abscopal effect during RT through activating tumor cell ferroptosis signals in bilateral HCC subcutaneous tumor mouse models, which could be significantly abolished by TLR3 knock-out or ferroptosis inhibitor ferrostatin-1. Moreover, poly(I:C) could promote the presentation of tumor neoantigens by dendritic cells to enhance the recruitment of activated CD8+ T cells into distant tumor tissues for inducing tumor cell ferroptosis during RT treatment. Finally, the safety and feasibility of combining poly(I:C) with RT for treating advanced HCC patients were further verified in a prospective clinical trial. Thus, enhancing TLR3 signaling activation during RT could provide a novel strategy for strengthening abscopal effect to improve the clinical benefits of advanced HCC patients.

Prognosis value of microscopic bile duct invasion in hepatocellular carcinoma: A multicenter study.

OBJECTIVE: To evaluate the prognostic significance of microscopic bile duct invasion (MiBDI) in hepatocellular carcinoma (HCC) following R0 resection. PATIENTS AND METHODS: Patients who underwent R0 resection for HCC at nine medical centers were stratified into five groups: neither bile duct nor vascular invasion (MiBDI-MVI-), microscopic bile duct invasion alone (MiBDI+MVI-), both microscopic bile duct and vascular invasion (MiBDI+MVI+), microscopic vascular invasion alone (MiBDI-MVI+), and macroscopic bile duct invasion (MaBDI). Overall survival (OS) was assessed using Kaplan-Meier analysis, and independent risk factors of OS were determined using Cox proportional hazards models. RESULTS: A total of 377 HCC cases were analyzed. The OS for MiBDI+MVI- was similar to that of MiBDI-MVI- (p > 0.05) but better than MiBDI+MVI+, MiBDI-MVI+, and MaBDI (all p < 0.05). Multivariate analysis indicated that MiBDI was not an independent risk factor for OS, while MVI and MaBDI were. CONCLUSIONS: Overall survival (OS) in patients with MiBDI was superior to those with MVI and MaBDI. Isolated MiBDI did not influence OS in patients with HCC after R0 resection.

Association of hepatitis B virus DNA levels with efficacy and safety outcomes in patients with hepatitis B virus-associated advanced hepatocellular carcinoma receiving tyrosine kinase inhibitor plus anti-PD-1 antibody: a multicenter propensity-matched study.

BACKGROUND: The efficacy and safety of tyrosine kinase inhibitors (TKIs) combined with anti-PD-1 antibodies (α-PD-1) in advanced hepatocellular carcinoma (HCC) with high hepatitis B virus (HBV) DNA levels (>500 IU/mL) remain unclear. METHODS: We retrospectively assessed patients from seven medical institutions diagnosed with HBV-related HCC, undergoing treatment with TKIs and α-PD-1 in conjunction with antiviral therapies. Based on HBV-DNA levels, patients were categorized into either high (HHBV-DNA, >500 IU/mL) or low HBV-DNA (LHBV-DNA, ≤500 IU/mL) cohorts Propensity score matching (PSM) was used to minimize baseline imbalance between groups. RESULTS: 149 patients were included, with 66 patients exhibiting HBV-DNA > 500 IU/mL and 83 patients presenting HBV-DNA ≤ 500 IU/mL. Compared with the LHBV-DNA cohort, the HHBV-DNA cohort had a greater incidence of serum HBeAg positivity, tumor diameter ≥ 10 cm, and vascular invasion. Following PSM, 57 individuals were enrolled in each group. Oncological outcomes were comparable between HHBV-DNA and LHBV-DNA cohorts before and after PSM. Before PSM, the median PFS and OS were 6.1 months and 17.5 months in the HHBV-DNA cohort and 6.7 months and 19.3 months in the LHBV-DNA cohort (all P > 0.05). After PSM, the median PFS and OS were 6.0 months and 19.5 months in the HHBV-DNA cohort and 6.0 months and 17.1 months in the LHBV-DNA cohort, respectively (all P > 0.05). Safety profiles were equivalent across cohorts with no fatal incidents reported. Seven patients (4.7 %) had HBV reactivation. 1 (0.7 %) from HHBV-DNA and 6 (4.0 %) from LHBV-DNA (P = 0.134). Only one patient developed HBV-related hepatitis. CONCLUSIONS: The effectiveness and safety of TKIs plus α-PD-1 in advanced HCC with HBV-DNA > 500 IU/mL were not compromised in the context of concomitant antiviral therapy.

Development and validation a radiomics nomogram for predicting thymidylate synthase status in hepatocellular carcinoma based on Gd-DTPA contrast enhanced MRI.

OBJECTIVES: The purpose of this study was to develop and validate a radiomics nomogram for predicting thymidylate synthase (TYMS) status in hepatocellular carcinoma (HCC) by using Gd-DTPA contrast enhanced MRI. METHODS: We retrospectively enrolled 147 consecutive patients with surgically confirmed HCC and randomly allocated to training and validation set (7:3). The TYMS status was immunohistochemical determined and classified into low TYMS (positive cells ≤ 25%) and high TYMS (positive cells > 25%) groups. Radiomics features were extracted from the arterial phases and portal venous phase of Gd-DTPA contrast enhanced MRI. Least absolute shrinkage and selection operator (LASSO) were applied for generating the Rad score. Clinical data and MRI findings were assessed to build a clinical model. Rad score combined with clinical features was used to construct radiomics nomogram. RESULTS: A total of 2260 features were extracted and reduced to 7 features as the most important discriminators to build the Rad score. InAFP was identified as the only independent clinical factors for TYMS status. The radiomics nomogram showed good discrimination in training (AUC, 0.759; 95% CI 0.665-0.838) and validation set (AUC, 0.739; 95% CI 0.585-0.860), and showed better discrimination capability (P < 0.05) compared with clinical model in training (AUC, 0.656; 95% CI 0.555-0.746) and validation set (AUC, 0.622; 95% CI 0.463-0.764). CONCLUSIONS: The radiomics nomogram shows favorable predictive efficacy for TYMS status in HCC, which might be helpful for the personalized treatment of HCC.

Prognostic significance of three-tiered pathological classification for microvascular invasion in patients with combined hepatocellular-cholangiocarcinoma following hepatic resection.

BACKGROUND AND OBJECTIVES: Previous studies have reported that the microvascular invasion three-tiered grading (MiVI-TTG) scheme is a better prognostic predictor than the two-tiered microvascular invasion (MiVI) grading scheme in hepatocellular carcinoma. This study aims to explore the prognostic significance of MiVI-TTG in patients undergoing liver resection for combined hepatocellular-cholangiocarcinoma (cHCC) and to explore the risk factors for MiVI in cHCC. METHODS: This research included 208 patients graded as M0, M1, or M2 using the MiVI-TTG scheme. Predictive performance was assessed by Cox regression analysis, Kaplan-Meier curve with Log rank test, Harrell's c-index, and time-dependent areas under the receiver operating characteristic curve (tdAUC). The clinical utility of the two schemes was evaluated by decision cure analysis (DCA). The risk factors for MiVI were evaluated using logistic regression analysis. RESULTS: Among 208 cHCC patients, the proportions of M0, M1 and M2 were 38.9%, 36.5%, and 24.5%, respectively. Patients with severe MiVI status had worse recurrence-free survival and overall survival (OS) based on Kaplan-Meier analysis. M1, M2, and MiVI-positive were independent risk factors for early recurrence, while M2 and MiVI-positive were associated with overall survival (OS). MiVI-TTG had a larger c-index, tdAUC, and net benefit rate than the two-tiered MiVI grading scheme for predicting recurrence free survival and OS. AFP≥400 ng/ml was the independent risk factor for MiVI, and satellite nodules were independent risk factors for M2. CONCLUSIONS: MiVI-TTG has a greater prognostic value than the two-tiered MiVI grading scheme in patients undergoing hepatic resection for cHCC.

Sanghuangporus vaninii fruit body polysaccharide alleviates hyperglycemia and hyperlipidemia via modulating intestinal microflora in type 2 diabetic mice.

The disease of type 2 diabetes mellitus (T2DM) is principally induced by insufficient insulin secretion and insulin resistance. In the current study, Sanghuangporus vaninii fruit body polysaccharide (SVP) was prepared and structurally characterized. It was shown that the yield of SVP was 1.91%, and SVP mainly contains small molecular weight polysaccharides. Afterward, the hypoglycemic and hypolipidemic effects and the potential mechanism of SVP in T2DM mice were investigated. The results exhibited oral SVP could reverse the body weight loss, high levels of blood glucose, insulin resistance, hyperlipidemia, and inflammation in T2DM mice. Oral SVP increased fecal short-chain fatty acids (SCFAs) concentrations of T2DM mice. Additionally, 16S rRNA sequencing analysis illustrated that SVP can modulate the structure and function of intestinal microflora in T2DM mice, indicating as decreasing the levels of Firmicutes/Bacteroidetes, Flavonifractor, Odoribacter, and increasing the levels of Weissella, Alloprevotella, and Dubosiella. Additionally, the levels of predicted metabolic functions of Citrate cycle, GABAergic synapse, Insulin signaling pathway were increased, and those of Purine metabolism, Taurine and hypotaurine metabolism, and Starch and sucrose metabolism were decreased in intestinal microflora after SVP treatment. These findings demonstrate that SVP could potentially play hypoglycemic and hypolipidemic effects by regulating gut microflora and be a promising nutraceutical for ameliorating T2DM.

A simplified model for prophylactic transarterial chemoembolization after resection for patients with hepatocellular carcinoma.

BACKGROUND: Prophylactic transarterial chemoembolization (p-TACE) is frequently conducted for patients with hepatocellular carcinoma (HCC) in China, but the question of who could benefit from it remains controversial. Hence, we wanted to establish a nomogram model to identify patients eligible for p-TACE. METHODS: Data from HCC patients receiving R0 resection with or without p-TACE between January 2013 and December 2014 were identified, using primary liver cancer big data, to establish a nomogram model to predict overall survival (OS). Based on the model, Patients receiving R0 resection between January 2015 and December 2015 were divided into three subgroups, and survival curves were constructed using the Kaplan-Meier method and analyzed by the log-rank test among patients in each subgroup. RESULTS: A nomogram integrating the neutrophil to lymphocyte ratio, AFP, tumor diameter, and microvascular invasion was developed to predict the OS of patients with HCC receiving R0 resection, and significant differences were observed in the median OS of the subgroups of low-risk (≤20), intermediate-risk (20~120), and high-risk (>120) identified by the current model. This model showed good calibration and discriminatory power in the validation cohort and the external cohort (c-index of 0.669 and 0.676, respectively). In the external cohort, the Kaplan-Meier curves showed that p-TACE could only significantly prolong the median OS of high-risk patients (25.6 vs. 33.7 months, P<0.05), but no differences were observed in any subgroups stratified by the current staging systems (all P>0.05). CONCLUSION: This readily available nomogram model could help guide decisions about p-TACE, but it needs further validation.

Comparative transcriptomics discloses the regulatory impact of carbon/nitrogen fermentation on the biosynthesis of Monascus kaoliang pigments.

Carbon and nitrogen play a fundamental role in the production of Monascus pigments. However, their effects on pigment biosynthesis remain undetermined. In this study, we found that Monascus kaoliang produces pigments via liquid fermentation using glycerol and peptone as suitable carbon and nitrogen sources, respectively. Comparative transcriptomic profiling was performed using RNA sequencing. It indicated that the differentially expressed genes (DEGs) of carbon were enriched using amino acids and carbohydrates via the transport and metabolism pathways, respectively. DEGs of nitrogen were enriched only using general functional prediction pathways. These data provide a comprehensive interpretation of the linkage between primary and secondary metabolisms in M. kaoliang. Moreover, they provide insights into the effects of various substances involved in secondary metabolism.

Postoperative Adjuvant Transarterial Chemoembolization Plus Tyrosine Kinase Inhibitor for Hepatocellular Carcinoma: a Multicentre Retrospective Study.

Purpose: This study aimed to assess the efficacy and safety of adjuvant transarterial chemoembolization (TACE) plus tyrosine kinase inhibitor (TKI) treatment in patients with hepatocellular carcinoma (HCC) with a high risk of early recurrence after curative resection. Patients and Methods: Patients from multiple centres were divided into postoperative adjuvant TACE with (n=57) or without (n=142) TKI administration groups. The disease-free survival (DFS) curve was depicted by the Kaplan-Meier method, and the difference between the two groups was tested using the log rank test. Univariate and multivariate Cox analyses were performed to identify independent risk factors for DFS. Additionally, three propensity score analyses were performed to minimise the potential confounding factors to facilitate a more reliable conclusion. Adverse events (AEs) were assessed according to the Common Terminology Criteria for Adverse Events, version 4.0. Results: The 1-and 2-year DFS rates of the TACE plus TKI treatment group were 45.5% and 34.9%, respectively, which were significantly better than those of the TACE alone group (26.8% and 18.3%, respectively). Multivariate analysis identified adjuvant TACE plus TKI treatment as an independent prognostic factor for DFS (hazard ratio: 0.611, 95% confidence interval: 0.408-0.915, P=0.017). Further analysis based on the various propensity score methods yielded similar results. Subgroup analysis showed that patients with tumour diameter ≥5 cm, tumour number <3, absence of hepatic vein tumour thrombus and bile duct tumour thrombus, ruptured tumours, and stage IIIB could benefit more from TACE plus TKI treatment (all P<0.05). Some patients (33.33%) experienced grade ≥3 AEs in the TACE plus TKI group. Conclusion: TACE plus TKI treatment can reduce the incidence of early recurrence with tolerable adverse events in HCC patients at high risk of recurrence after hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment.

Redefining Hepatocellular Carcinoma Staging Systems Based on the Bile Duct Invasion Status: A Multicenter Study.

BACKGROUND AND AIMS: The prognostic value of bile duct invasion (BDI) remains controversial. We aimed to investigate the prognostic value of BDI and the stage of BDI in different staging systems. METHODS: Patients with hepatocellular carcinoma (HCC) from nine hepatobiliary medical centers who underwent R0 resection were included. Overall survival (OS) was assessed using the Kaplan-Meier method and tested using the log-rank test. The prognostic effect of BDI was analyzed using univariate and multivariate Cox proportional hazard regression analyses. The predictive performance of these models was evaluated using the concordance index and time-dependent receiver operating characteristic curve (tdAUC). RESULTS: Of 1021 patients with HCC, 177 had BDI. OS was worse in the HCC with BDI group than in the HCC without BDI group (p<0.001); multivariate analysis identified BDI as an independent risk factor for OS. After adjustment for interference of confounding factors using the Cox proportional hazard regression model, HCC with BDI and without macrovascular invasion was classified as Barcelona Clinic Liver Cancer (BCLC) B, eighth edition American Joint Committee on Cancer (AJCC) IIIA, and China Liver Cancer (CNLC) IIb, respectively, whereas HCC with BDI and macrovascular was classified as BCLC C, AJCC IIIB, and CNLC IIIA, respectively. C-indexes and tdAUCs of the adjusted staging systems were superior to those of the corresponding current staging systems. CONCLUSION: We constructed adjusted staging systems with the BDI status, improved their predictive performance and facilitate clinical use.

Prognostic and Predictive Value of Transcription Factors Panel for Digestive System Carcinoma.

PURPOSE: Digestive system carcinoma is one of the most devastating diseases worldwide. Lack of valid clinicopathological parameters as prognostic factors needs more accurate and effective biomarkers for high-confidence prognosis that guide decision-making for optimal treatment of digestive system carcinoma. The aim of the present study was to establish a novel model to improve prognosis prediction of digestive system carcinoma, with a particular interest in transcription factors (TFs). MATERIALS AND METHODS: A TF-related prognosis model of digestive system carcinoma with data from TCGA database successively were processed by univariate and multivariate Cox regression analyses. Then, for evaluating the prognostic prediction value of the model, ROC curve and survival analysis were performed by external data from GEO database. Furthermore, we verified the expression of TFs expression by qPCR in digestive system carcinoma tissue. Finally, we constructed a TF clinical characteristics nomogram to furtherly predict digestive system carcinoma patient survival probability with TCGA database. RESULTS: By Cox regression analysis, a panel of 17 TFs (NFIC, YBX2, ZBTB47, ZNF367, CREB3L3, HEYL, FOXD1, TIGD1, SNAI1, HSF4, CENPA, ETS2, FOXM1, ETV4, MYBL2, FOXQ1, ZNF589) was identified to present with powerful predictive performance for overall survival of digestive system carcinoma patients based on TCGA database. A nomogram that integrates TFs was established, allowing efficient prediction of survival probabilities and displaying higher clinical utility. CONCLUSION: The 17-TF panel is an independent prognostic factor for digestive system carcinoma, and 17 TFs based nomogram might provide implication an effective approach for digestive system carcinoma patient management and treatment.

Exploring the clinical value of preoperative serum gamma-glutamyl transferase levels in the management of patients with hepatocellular carcinoma receiving postoperative adjuvant transarterial chemoembolization.

BACKGROUND: Preoperative serum gamma-glutamyl transferase (γ-GT) levels is significantly related to the prognosis of hepatocellular carcinoma (HCC), but its clinical value in the management of postoperative adjuvant transarterial chemoembolization (PA-TACE) has rarely been explored. This study aimed to investigate whether γ-GT levels could be taken as a biomarker to guide the management of PA-TACE in resectable HCC. METHODS: HCC patients receiving radical resection were identified through the primary liver cancer big data (PLCBD) from December 2012 to December 2015. Prognostic factors of overall survival (OS) and disease-free survival (DFS) were identified by univariate and multivariate cox analyses, and subgroup analysis was conducted between PA-TACE group and non-TACE stratified by γ-GT levels before and after 1:1 propensity score matching (PSM). RESULTS: γ-GT level was found to be an independent risk factor of OS and DFS in 1847 HCC patients receiving radical resection (both P < 0.05), and patients with elevated γ-GT(> 54.0 U/L) have a shortened median OS and DFS, compared with those with normal γ-GT (both P < 0.001). In the subgroup of patients with normal γ-GT, there were no significant differences between groups of PA-TACE and non-TACE in terms of median OS and DFS before and after PSM (all P > 0.05), and PA-TACE was not a significant prognostic factor of both OS and DFS before and after PSM (all P > 0.05). In the subgroup of patients with elevated γ-GT, significant differences were found between groups of PA-TACE and non-TACE in terms of median OS and DFS before and after PSM (all P < 0.05), and PA-TACE was an independent prognostic factor of both OS and DFS (all P < 0.05). CONCLUSION: Currently, we concluded that patients with more advanced HCC also have more elevated γ-GT, and these patients with elevated γ-GT would be benefited more from PA-TACE after radical resection.

Impact of surgical margin width on long-term outcomes for intrahepatic cholangiocarcinoma: a multicenter study.

BACKGROUND: The objective of this study was to investigate the survival outcomes of surgical margin width in intrahepatic cholangiocarcinoma (ICC). METHODS: Between November 2011 and August 2017, patients who underwent hepatectomy for ICC were collected from 13 major hepatopancreatobiliary centers in China. The survival outcomes for patients who underwent wide margin hepatectomy (WMH) were compared with those who underwent narrow margin hepatectomy (NMH) using the 1:1 propensity score matching (PSM). RESULTS: Among 478 included patients, 195 (40.8%) underwent WMH whereas 283 (59.2%) underwent NMH. PSM yielded 79 matched patients with similar baseline characteristics. Patients underwent WMH had a significant better OS and DFS compared with those underwent NMH (before PSM: median OS 27 vs 17 months, P < 0.05; median DFS 15 vs 8 months, P = 0.001, after PSM: median OS 41 vs 22 months, p < 0.05; median DFS 16 vs 10 months, p < 0.05). However, subgroup analysis based on the AJCC staging system, WMH could only improve the survival outcomes in AJCC I ICC patients (Stage I: OS, DFS, P<0.05). CONCLUSIONS: Surgeons should strive to achieve a wide surgical margin for patients with AJCC I ICC to optimize the long-term outcome.

Radiofrequency ablation versus repeat hepatectomy in the treatment of recurrent hepatocellular carcinoma in subcapsular location: a retrospective cohort study.

BACKGROUND: Repeat hepatectomy and radiofrequency ablation (RFA) are widely used to treat early recurrent hepatocellular carcinoma (RHCC) located in the subcapsular region, but the optimal treatment strategy remains to be controversial. METHODS: A total of 126 RHCC patients in the subcapsular location after initial radical hepatectomy were included in this study between Dec 2014 and Jan 2018. These patients were divided into the RFA group (46 cases) and the repeat hepatectomy group (80 cases). The primary endpoints include repeat recurrence-free survival (rRFS) and overall survival (OS), and the secondary endpoint was complications. The propensity-score matching (PSM) was conducted to minimize the bias. Complications were evaluated using the Clavien-Dindo classification, and severe complications were defined as classification of complications of ≥grade 3. RESULTS: There were no significant differences in the incidence of severe complications were observed between RFA group and repeat hepatectomy group in rRFS and OS both before (1-, 2-, and 3-year rRFS rates were 65.2%, 47.5%, and 33.3% vs 72.5%, 51.2%, and 39.2%, respectively, P = 0.48; 1-, 2-, and 3-year OS rates were 93.5%, 80.2%, and 67.9% vs 93.7%, 75.8%, and 64.2%, respectively, P = 0.92) and after PSM (1-, 2-, and 3-year rRFS rates were 68.6%, 51.0%, and 34.0% vs 71.4%, 42.9%, and 32.3%, respectively, P = 0.78; 1-, 2-, and 3-year OS rates were 94.3%, 82.9%, and 71.4% vs 88.6%, 73.8%, and 59.0%, respectively, P = 0.36). Moreover, no significant differences in the incidence of severe complications were observed between the RFA group and repeat hepatectomy group. CONCLUSION: Both repeat hepatectomy and RFA are shown to be effective and safe for the treatment of RHCC located in the subcapsular region.

An MR-based radiomics model for differentiation between hepatocellular carcinoma and focal nodular hyperplasia in non-cirrhotic liver.

PURPOSE: We aimed to develop and validate a radiomics model for differentiating hepatocellular carcinoma (HCC) from focal nodular hyperplasia (FNH) in non-cirrhotic livers using Gd-DTPA contrast-enhanced magnetic resonance imaging (MRI). METHODS: We retrospectively enrolled 149 HCC and 75 FNH patients treated between May 2015 and May 2019 at our center. Patients were randomly allocated to a training (n=156) and validation set (n=68). In total, 2260 radiomics features were extracted from the arterial phase and portal venous phase of Gd-DTPA contrast-enhanced MRI. Using Max-Relevance and Min-Redundancy, random forest, least absolute shrinkage, and selection operator algorithm for dimensionality reduction, multivariable logistic regression was used to build the radiomics model. A clinical model and combined model were also established. The diagnostic performance of the models was compared. RESULTS: Eight radiomics features were chosen for the radiomics model, and four clinical factors (age, sex, HbsAg, and enhancement pattern) were chosen for the clinical model. A combined model was built using the factors from the previous models. The classification accuracy of the combined model differentiated HCC from FNH in both the training and validation sets (0.956 and 0.941, respectively). The area under the receiver operating characteristic curve of the combined model was significantly better than that of the clinical model for both the training (0.984 vs. 0.937, p=0.002) and validation (0.972 vs. 0.903, p=0.032) sets. CONCLUSIONS: The combined model provided a non-invasive quantitative method for differentiating HCC from FNH in non-cirrhotic liver with high accuracy. Our model may assist clinicians in the clinical decision-making process.

Lenvatinib Plus Camrelizumab versus Lenvatinib Monotherapy as Post-Progression Treatment for Advanced Hepatocellular Carcinoma: A Short-Term Prognostic Study.

OBJECTIVE: Compared the outcomes between lenvatinib plus camrelizumab therapy and lenvatinib monotherapy as post-progression treatment for advanced hepatocellular carcinoma (HCC) with progressive disease (PD). PATIENTS AND METHODS: A total of 48 advanced HCC patients were included in this retrospective study between June 2019 and March 2020. The patients were divided into the lenvatinib plus camrelizumab group (n=21) and the lenvatinib group (n=27). Primary endpoints were overall survival (OS) and progression-free survival (PFS), and secondary endpoints were the objective response rate (ORR) and adverse events (AEs). RESULTS: The median follow-up time was 8.4 months. The median OS was not obtained. The median PFS of lenvatinib plus camrelizumab group was significantly longer than that of lenvatinib group (8.0 months vs 4.0 months, p=0.011). Compared with lenvatinib group, lenvatinib plus camrelizumab group had higher ORR (28.57% vs 7.41%) and disease control rate (DCR) (71.43% vs 51.85%). The most common adverse events (AEs) included hand-foot skin reaction, hypertensions and abnormal hepatic function damage. Overall, 23.81% and 25.93% of patients experienced grade ≥3AEs in the lenvatinib plus camrelizumab group and the lenvatinib group, respectively. CONCLUSION: Lenvatinib plus camrelizumab as post-progression treatment is effective and safe for advanced hepatocellular carcinoma with PD.

Extraction of alumina from aluminum dross by a non-hazardous alkaline sintering process: Dissolution kinetics of alumina and silica from calcined materials.

The aluminum dross (AD), which causes numerous problems of its management and disposal to environment is a useful resource to extract alumina. This study explains a novel process to extract highly pure alumina (Al2O3) from AD at a high extraction rate without producing the residues and exhaust gases. An experimental set up was designed to perform the grinding of AD for the decomposition of aluminum nitride (AlN) and the removal of salts. Thereby, the desalted dross was used to detect the optimum alkaline (NaOH) calcination parameters and leaching conditions, as well as the dissolution kinetics of alumina and silica. The leaching residues were used to produce Ettringite mineral with calcium-based compounds (including CaO and CaSO4) to avoid the problems of solid waste disposal from the leaching process. Moreover, to purify the alumina, slightly soluble CaSO4 was added in leaching solution to precipitate silicate and the optimum additive/solution ratio (g/mL) was determined. The aluminum hydroxide (Al(OH)3), precipitated after the carbonization was calcinated at 900.0 °C for 2 h to produce γ-alumina. The morphological and mineralogical characterizations of AD, γ-Al2O3 and the synthesized Ettringite mineral were studied by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and X-ray fluorescence (XRF). It was observed that activation temperature of 1000.0 °C, Na2O/Al2O3 molar ratio of 1.4, leaching temperature of 60.0 °C, leaching time of 40.0 min, and the leaching liquid/solid ratio (mL/g) of 25/1 were the optimal parameter conditions to extract alumina with the extraction rate at 86.7% and purity of more than 98%. The results of leaching kinetics' study showed that the dissolution of alumina and silica were both controlled by layer diffusion process with the apparent activation energy of 11.4010 kJ·mol-1 and 2.0556 kJ·mol-1, respectively.

Pre- and Postoperative Models for Prediction of Recurrence in Non-B, Non-C Hepatocellular Carcinoma.

BACKGROUND AND AIMS: The incidence of non-B, non-C hepatocellular carcinoma (NBNC-HCC) is increasing. Like in hepatitis B virus (HBC)/HCV-associated HCC, treatment of NBNC-HCC after resection is challenging due to its high recurrence rate. However, few studies on the recurrence of NBNC-HCC have been published in the past decades. Hence, we aimed to investigate the risk factors for recurrence of NBNC-HCC and construct pre- and postoperative prognostic models for predicting recurrence in these patients who underwent curative resection. METHODS: We retrospectively analyzed 608 patients who underwent liver resection for NBNC-HCC. A multivariate Cox proportional hazard regression analysis was conducted to identify the independent risk factors of recurrence, based on which the prediction nomogram models were constructed and validated. The predictive performance of the models was assessed using the concordance index, time-dependent receiver operating characteristic curve, prediction error cure, and calibration curve. To facilitate clinical use, we stratified the patients into three distinct risk groups based on the score of the models. The cutoff scores of the models were determined by a survival tree analysis. RESULTS: Multivariable analysis identified neutrophil-to-lymphocyte ratio, alpha fetoprotein, tumor number, and tumor diameter as independent preoperative risk factors for recurrence. In addition to these variables, microvascular invasion was an independent postoperative risk factor for recurrence. The pre- and postoperative nomograms were constructed based on these variables. The C-index of the pre- and postoperative nomograms was 0.689 and 0.702 in the training cohort, 0.682 and 0.688 in the validation cohort, respectively, which were both higher than those of the conventional Barcelona Clinic Liver Cancer (BCLC) and 8th edition of the American Joint Committee on Cancer (AJCC8th) staging systems. In addition, the pre- and postoperative nomograms could also re-stratify patients with BCLC stage 0/A or AJCC8th stage IA/IB/II into distinct risk groups. CONCLUSIONS: We constructed pre- and postoperative prognostic models for predicting recurrence in patients with NBNC-HCC who underwent curative resection. They can play a supplementary role to the traditional staging system.

Clinical Significance of Alpha-Fetoprotein in Alpha-Fetoprotein Negative Hepatocellular Carcinoma Underwent Curative Resection.

BACKGROUND: The clinical value of alpha-fetoprotein (AFP) in patients with AFP-negative (< 20 ng/ml) hepatocellular carcinoma (HCC) who underwent curative resection remained controversial. AIMS: To investigate clinical relevance and prognostic effect of preoperative serum AFP level in this subgroup. METHODS: A total of 1879 patients with AFP-negative HCC who underwent curative resection were included in the study. Overall survival (OS) and disease-free survival (DFS) rate were displayed by Kaplan-Meier method and compared by log-rank test. Multivariate cox proportional hazard regression analysis was used to identify the independent prognostic factors. The prognostic predictive performance was analyzed by time-dependent areas under receiver operating characteristic curve (AUC). RESULTS: Even in AFP-negative HCC, patients with high preoperative serum AFP level tended to have multiple tumor (P < 0.001), poorer differentiation of tumor cell (P < 0.001), presence of satellite nodules (P < 0.001), and MVI (P = 0.002). Kaplan-Meier analysis showed the adverse impact of AFP level on prognosis, especially for DFS. Multivariate analysis identified AFP as the independent unfavorable factor for OS and DFS (P < 0.001 for both). Time-dependent AUC analysis showed that the combination with AFP could improve the prognostic predictive performance of 8th AJCC and BCLC staging system. CONCLUSIONS: AFP was still the surrogate of aggressive behavior of HCC and independent prognostic factor for patients with AFP-negative HCC underwent curative resection. Even combining with such a low level of AFP could significantly improve the predictive performance of conventional staging system.