Risk of HCC decreases in HBV-related patients with cirrhosis acquired recompensation: A retrospective study based on Baveno VII criteria.

BACKGROUND: Antiviral therapy improves the clinical outcomes of patients with HBV-related cirrhosis. In this study, we aimed to evaluate the incidence rate of HCC in patients with HBV-related recompensated, compensated, or decompensated cirrhosis based on the latest Baveno VII criteria. METHODS: In this two-center retrospective study, HBV-related patients with cirrhosis were enrolled and treated with first-line nucleos(t)ide analogues therapy for at least 12 months. Participants were classified into 3 groups: (1) compensated group, (2) decompensated group, or (3) recompensated group according to Baveno VII criteria. Multivariate regression models and propensity score matching were used to identify the predictors of HCC. RESULTS: Of the 404 patients recruited, during a median follow-up of 44.5 months (interquartile range 26.8, 57.0 months), 233 (57.7%), 100 (24.8%), and 71(17.6%) patients had compensated, recompensated, and decompensated cirrhosis. In total, 38 developed HCC. The cumulative incidence of HCC development at 2, 4, and 6 years was 1.3%, 5.4%, and 20.0% in the compensated group, 1.2%, 5.2%, and 24.5% in the recompensated group, and 2.1%, 23.6%, and 41.8% in the decompensated group, respectively. In the multivariate Cox regression model, compared with the recompensated group, the decompensated group had a significant increased risk for the development of HCC (aHR 2.55; 95% CI: 1.240-5.240; p = 0.027), while the compensated group had similar HCC risk for the development of HCC (aHR 1.41; 95% CI: 0.540-3.730; p = 0.835). Propensity score-matching analysis between the recompensated and compensated groups (84 pairs) and propensity score-matching analysis between the recompensated and decompensated groups (62 pairs) showed similar results. CONCLUSIONS: Achieving recompensation reduced the risk of HCC in patients with HBV-related decompensated cirrhosis, while the risk remained comparable to that of compensated cirrhosis.

Research on quality evaluation of innovation and entrepreneurship education for college students based on random forest algorithm and logistic regression model.

The quality evaluation of innovation and entrepreneurship (I&E) in the education sector is achieving worldwide attention as empowering nations with high quality talents is quintessential for economic progress. China, a pioneer in the world market in almost all sectors have transformed its educational policies and incorporated entrepreneurial skills as a part of their education models to further catalyst the country's economic progress. This research focuses on building a novel hybrid Machine Learning (ML) model by integrating two powerful algorithms namely Random Forest (RF) and Logistic Regression (LR) to assess the intensity of the I&E in education from the data acquired from 25 leading Higher Educational Institution's (HEI) in different provinces. The major contributions to the work are, (1) construction of quality index for each topic of interest using individual RF, (2) ranking the indicators based on the quality index to assess the strength and weaknesses, (3) and finally use the LR algorithm study the quality of each indicator. The efficacy of the proposed hybrid model is validated using the benchmark classification metrics to assess its learning and prediction performance in evaluating the quality of I&E education. The result of the research portrays that the universities have now started to integrate entrepreneurship skills as a part of the curriculum, which is evident from the better ranking of the topic curriculum development which is followed by the enrichment of skills. This comprehensive research will help the institutions to identify the potential areas of growth to boost the economic development and improve the skill set necessary for I&E education among college students.

Multivalent SnO2 quantum dot-decorated Ti3C2 MXene for highly sensitive electrochemical detection of Sudan I in food.

Quantum dots functionalization has been proven to be a simple modification strategy for improving the electroanalytical performance of two-dimensional electrode materials by increasing the specific surface area and active reaction sites. Herein, a new electrochemical sensing platform was fabricated by SnO2 quantum dot-functionalized Ti3C2 MXene (Ti3C2-SnO2QDs) for the highly sensitive detection of Sudan I in food. Ti3C2-SnO2QDs were prepared via in situ synthesis, which can control the nucleation and growth of SnO2QDs, resulting in the well-dispersed SnO2QDs with 2-3 nm size on the intersheet surface of MXene. Moreover, the formation of Ti3C2-SnO2QDs can effectively restrict the aggregation of Ti3C2 and improve the stability of SnO2QDs in aquatic environment. The prepared nanocomposite can be used as an improved modified material to further increase the electrocatalytic performance and electrochemical signal of Sudan I on the surface of a glassy carbon electrode. Under optimized conditions, the proposed analytical method displayed a linear dependence for Sudan I concentration ranging from 0.008 to 10 µM with a detection limit of 0.27 nM (S/N = 3) by electrochemical cyclic voltammetry. This sensor with excellent selectivity, reproducibility and accuracy was quantitatively validated in commercial ketchup and chili powder. This Ti3C2-SnO2QDs-based Sudan I sensor is expected to expand the application of MXene nanocomposites in electrochemical analysis and is envisioned as a promising candidate for monitoring illegal food additives in real food samples.

Big Data-Driven Vocational Undergraduate Talent Training and Social Needs Adaptability Analysis and Collaborative Path Mining.

Aiming at the problem of mismatch between talent cultivation and social demand in the process of undergraduate education, this paper proposes a big data-driven method of adaptability analysis and collaborative path mining between vocational undergraduate talent cultivation and social demand. Starting from the big data-driven vocational undergraduate talent training and social needs, this paper points out the problems existing in the current social needs and puts forward the basic framework of vocational undergraduate talent training mode. Secondly, the clustering model of talent training and social demand is analyzed, and the clustering mining method is proposed. Finally, the big data-driven personnel training and social adaptation mining analysis, in their own ability and social needs adaptability analysis, the basic adaptation accounted for a higher proportion. Professional competence has a higher trust value in cluster analysis. Today's social employment situation is becoming more and more severe, and how to enhance the quality of profession undergraduate students has become one of the theoretical and practical issues worthy of attention in China's colleges at this stage. The talent training model of colleges and universities is closely in route with the demands of society, and the problem of student hire is prominent. Therefore, this paper proposes a student employability training program that combines the elements of student employability through social needs research.

Animal naming test for the assessment of minimal hepatic encephalopathy in Asian cirrhotic populations.

BACKGROUND AND AIM: To evaluate the diagnostic performance of simplified animal naming test (S-ANT1) for minimal hepatic encephalopathy (MHE) in patients with cirrhosis from a Chinese tertiary centre and to optimize the application strategy of S-ANT1 in clinical practice. METHODS: The Animal Naming Test 1 (ANT1) was performed in all included cirrhotic patients and healthy volunteers. S-ANT1 was calculated to adjust for age and education. Psychometric Hepatic Encephalopathy Score (PHES) was also performed in patients with cirrhosis. RESULTS: 88 cirrhotic patients and 34 healthy control subjects were included. Cirrhotic patients were characterized with lower S-ANT1 scores (P =  0.001). In patients with cirrhosis, score of S-ANT1 was correlated with PHES score, age, school education period, and blood ammonia (all P values <0.05). With ≤20 animals as the cut-off value, S-ANT1 could distinguish MHE and no MHE with a sensitivity of 77.5% and a specificity of 58.3%. A three-step screening strategy, with 90% as a threshold for sensitivity and specificity and two cut-off values "≤12 animals" and ">23 animals", was then formulated to rule out patients with high possibility of MHE and with high possibility of no MHE. The remaining "ruled-in" patients should be further evaluated for MHE using PHES. CONCLUSIONS: S-ANT1 is an important screening tool for MHE in cirrhotic patients. The three-step screening strategy based on S-ANT1 and PHES is conducive to the identification of MHE in clinical practice.

Photo-initiated enhanced antibacterial therapy using a non-covalent functionalized graphene oxide nanoplatform.

This study describes a novel antibacterial phototherapeutic platform for highly efficient healing of bacteria-infected wounds. It is based on the photodynamic and physical actions of a zinc tetraaminophthalocyanine-modified graphene oxide nanocomposite produced via non-covalent functionalization. The nanocomposite is positively charged and can easily capture negatively charged bacteria via electrostatic interactions. The antibacterial action is two-fold: (1) reactive oxygen species are produced by the phthalocyanine photosensitizer after short-term exposure to 680 nm light and (2) the graphene oxide can physically cut bacterial cell membranes. These enhanced activities can kill Gram-positive and Gram-negative bacteria at very low dosages. An ultrastructural examination indicates that this nanocomposite causes enormous damage to bacterial morphology and leakage of intracellular substances that lead to bacterial death. A rat wound model is used to demonstrate that the proposed phototherapeutic platform has low cytotoxicity and can promote rapid healing in bacteria-infected wounds. These results suggest that the integration of different antibacterial methods into a single nanotherapeutic platform is a promising strategy for anti-infective treatment.

Multivalent and synergistic chitosan oligosaccharide-Ag nanocomposites for therapy of bacterial infection.

Chitosan oligosaccharide functionalized silver nanoparticles with synergistic bacterial activity were constructed as a multivalent inhibitor of bacteria. Placing the chitosan oligosaccharide on silver nanoparticles can dramatically enhance the adsorption to the bacterial membrane via multivalent binding. The multicomponent nanostructures can cooperate synergistically against gram-positive and gram-negative bacteria. The antibacterial activity was increased via orthogonal array design to optimize the synthesis condition. The synergistic bacterial activity was confirmed by fractional inhibitory concentration and zone of inhibition test. Through studies of antimicrobial action mechanism, it was found that the nanocomposites interacted with the bacteria by binding to Mg2+ ions of the bacterial surface. Then, the nanocomposites disrupted bacterial membrane by increasing the permeability of the outer membrane, resulting in leakage of cytoplasm. This strategy of chitosan oligosaccharide modification can increase the antibacterial activity of silver nanoparticles and accelerate wound healing at the same time. The nanomaterial without cytotoxicity has promising applications in bacteria-infected wound healing therapy.

Entecavir and Low Genetic Barrier Antiviral Agents for Hepatocellular Carcinoma in Hepatitis B Viral Cirrhosis: Propensity Score Matching.

OBJECTIVE: To compare the reduction of hepatocellular carcinoma (HCC) risk between long-term treatment of entecavir and low genetic barrier antiviral agents in hepatitis B virus (HBV)-related cirrhotic patients. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Department of Infectious Diseases and Hepatology, the Second Hospital of Shandong University, Jinan, China, from October 2008 to October 2016. METHODOLOGY: HBV-related cirrhotic patients with antiviral treatment for at least 12 months were consecutively included. Propensity score matching analysis was performed to improve comparability of the data from both entecavir group and the control group. Log-rank test was used to compare influence of various nucleos(t)ide analogs (NAs) for incidence of HCC. Independent risk factors were estimated by multivariable Cox proportional hazards models. RESULTS: The total cohort included 207 HBV-related cirrhotic patients, of which 83 patients were treated with entecavir initially. The present study found no statistical difference for the incidence of HCC between entecavir group and the control group in the total cohort (p=0.525). However, the difference became statistically significant (p=0.014) after propensity score matching. Number needed to treat (NNT) were 8 patients, 6 patients and 3 patients at years 2, 3 and 4, respectively. Multivariable Cox regression in propensity score matching cohort revealed older age (HR: 1.066, p=0.041), NAs of low generic barrier (HR: 6.944, p=0.016), NAs resistance (HR: 3.648, p=0.041), and lower platelet counts (<80x10 9/L) (HR: 6.718, p=0.009) as independent risk factors for HCC incidence. CONCLUSION: Entecavir is more efficient in reducing the incident HCC risk for HBV-related cirrhotic patients in comparison to low genetic barrier NAs.

Serum Macroelement and Microelement Concentrations in Patients with Polycystic Ovary Syndrome: a Cross-Sectional Study.

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine diseases. However, its pathogenesis is unclear. We aim to explore the potential relationships between serum macroelements/microelements and PCOS. A total of 1137 women were involved in the current study. PCOS was defined according to ESHRE/ASRM, and complete blood samples were collected. Serum macroelements (calcium and magnesium) and microelements (copper, zinc, and iron) were assayed through atomic absorption spectrophotometry. PCOS patients had significantly higher copper concentrations than patients without PCOS (P < 0.001). By contrast, PCOS patients had lower serum calcium levels than patients without PCOS (P < 0.001). No significant differences were observed in the levels of serum zinc, magnesium, and iron between PCOS and non-PCOS patients. PCOS patients with acne had higher magnesium levels than those without acne (P = 0.020), and PCOS patients with hirsutism had lower magnesium levels than those without hirsutism (P = 0.037). High serum copper and low calcium levels may be correlated with PCOS. Magnesium concentrations are correlated with acne and hirsutism in PCOS patients. These results provide clues to explore the mechanism of PCOS and guidance for element treatments in PCOS patients.

Genistein inhibits hepatocellular carcinoma cell migration by reversing the epithelial-mesenchymal transition: partial mediation by the transcription factor NFAT1.

To investigate the effects and mechanism of genistein on hepatocellular carcinoma. Cell counting kit-8 assays showed that genistein at 3, 6, and 9 µM had no significant cytotoxic effects on HepG2, SMMC-7721, and Bel-7402 cells. Cell scratch and Transwell assays identified that genistein inhibited migration of three cell lines. In three cell lines, genistein enhanced E-cadherin and α-catenin, but reduced N-cadherin and Vimentin at both mRNA and protein levels in a dose-dependent manner. Simultaneously, treatment with genistein suppressed epithelial-mesenchymal transition (EMT) induced by TGF-ß. In HepG2 cells, genistein reduced mRNA, and protein expressions of nuclear factor of activated T cells 1 (NFAT1), Abca3, Autotaxin, CD154, and Cox-2. Phorbol 12-myristate 13-acetate (PMA) and ionomycin enhanced activity of NFAT1, reduced E-cadherin and α-catenin protein levels, and increased protein levels of N-cadherin and Vimentin. Transwell demonstrated that PMA and ionomycin reversed the migration inhibitory effects of genistein on HepG2 cells. In vivo, genistein inhibited the intrahepatic metastasis by reversing the EMT, which was correlated with reduced NFAT1 . Genistein inhibited hepatocellular carcinoma cell migration by reversing the EMT, which was partly mediated by NFAT1. The fact that EMT can be reversed by genistein may shed light on the possible mechanisms for its role in liver cancer therapy.

Ethyl pyruvate pretreatment attenuates concanavalin a-induced autoimmune hepatitis in mice.

PHARMACOLOGICAL RELEVANCE: Ethyl pyruvate (EP), a potent reactive oxygen species scavenger, has been reported to contribute to the inflammatory process. However, the protective effect of ethyl pyruvate on Concanavalin A (Con A)-induced autoimmune hepatitis have not been explored. Thus, the aims of this study are to investigate both the effects of ethyl pyruvate and its mechanism of protection on Con A-induced autoimmune hepatitis in mice. MATERIALS AND METHODS: Acute autoimmune hepatitis was induced by Con A (20 mg/kg) in Balb/C mice; ethyl pyruvate (40 mg/kg and 80 mg/kg) was administrated 1h prior to the Con A injection. At 3h, 6h and 24h post Con A injection, histological grading, proinflammatory cytokine levels and nuclear factor kappa B (NF-κB) activity were determined. RESULTS: Following Con A challenge, cytokines TNF-α, IL-2, IL-1ß and IL-6 were expressed at 3h and 6h, and the level of HMGB1 significantly increased by 24h. Pretreatment with ethyl pyruvate ameliorated the pathological effects of Con A-induced autoimmune hepatitis and significantly decreased the levels of TNF-α, IL-2, IL-6 and IL-1ß at 3h and 6h and the level of HMGB1 at 6h and 24h post injection. Ethyl pyruvate blocked the degradation of IκB α and IκB ß and decreased the expression of NF-κB at 24h. CONCLUSION: Taken together, these results indicated that ethyl pyruvate protected against Con A-induced autoimmune hepatitis by decreasing both early (TNF-α, IL-2, IL-1ß and IL-6) and late (HMGB1) cytokine expression in mice. The reduction of HMGB1 may correlate with the amelioration of NF-κB activity.

Protective effects of necrostatin-1 against concanavalin A-induced acute hepatic injury in mice.

OBJECTIVE: Necrostatin-1 (Nec-1) inhibits receptor-interacting protein 1 (RIP1) kinase and programmed necrosis. This study was designed to examine the protective effects and mechanisms of Nec-1 in concanavalin A- (ConA-) induced hepatitis in mice. METHODS: C57BL/6 mice were exposed to ConA via tail vein injection and injected intraperitoneally with Nec-1 or vehicle. Levels of serum liver enzymes and histopathology were determined. Levels of inflammatory cytokines with ConA-induced hepatitis were determined with real-time polymerase chain reaction (real-time PCR). The expression of TNF- α , RIP1, and LC3 was detected with immunohistochemical staining. The expression of TNF- α , IFN- γ , IL2, IL6, caspase 3, RIP1, beclin-1, and LC3 protein was assessed by immunofluorescence and western blotting. Autophagosomes were observed with transmission electron microscopy (TEM). RESULTS: Amelioration in liver functions and histopathological changes and the suppression of inflammatory cytokine production were observed in Nec-1-injected mice. Western blotting analysis showed that the expression of TNF- α , IFN- γ , IL2, IL6, and RIP1 was significantly reduced in the Nec-1-injected mice, which was confirmed by immunofluorescence and immunohistochemistry. Autophagosome formation was significantly reduced by Nec-1 treatment, as the expression of beclin-1 and LC3, determined with immunofluorescence and western blotting. CONCLUSION: These results demonstrate that Nec-1 prevents ConA-induced liver injury via RIP1-related and autophagy-related pathways.

Mechanism of action of salinomycin on growth and migration in pancreatic cancer cell lines.

OBJECTIVES: Pancreatic cancer is one of the most aggressive and lethal cancers worldwide and there are few effective treatments. Recently, salinomycin (Sal) was reported to alter proliferation and apoptosis in various tumors. This prompted us to investigate the effect of Sal on pancreatic cancer cells and to explore the possible molecular mechanism in vitro. METHODS: After treatment with Sal, pancreatic cancer cell viability and apoptosis were analyzed by Hoechst 33342 staining and flow cytometry, respectively. Invasion and metastasis of pancreatic cancer cells were assayed by a Transwell migration assay. Flow cytometry was also used to assessed the fraction of CD133(+) cell subpopulations. The expression of proliferating cell nuclear antigen (PCNA), Bcl-2, E-cadherin, and Wnt/ß-catenin signaling-related proteins were detected by RT-PCR and western blot. RESULTS: Sal inhibited the growth and migration of pancreatic cancer cells in vitro in a dose- and time-dependent manner. We found that the proportion of CD133(+) cell subpopulations decreased after treatment with Sal in pancreatic cancer cell lines at the same time. The percentage of apoptotic cells was increased after Sal treatment. Compared with control groups, Bax and E-cadherin were significantly upregulated, and Bcl-2 and PCNA were significantly downregulated in Sal-treated cells. The expression of Wnt/ß-catenin signaling-related proteins (ß-catenin and p-GSK-3ß) was inhibited. CONCLUSIONS: These results indicate that Sal could influence the cell growth and migration in pancreatic cancer cells in vitro, which may occur by inhibition of Wnt/ß-catenin signaling.

Salinomycin inhibits proliferation and induces apoptosis of human hepatocellular carcinoma cells in vitro and in vivo.

The anti-tumor antibiotic salinomycin (Sal) was recently identified as a selective inhibitor of breast cancer stem cells; however, the effect of Sal on hepatocellular carcinoma (HCC) is not clear. This study aimed to determine the anti-tumor efficacy and mechanism of Sal on HCC. HCC cell lines (HepG2, SMMC-7721, and BEL-7402) were treated with Sal. Cell doubling time was determinated by drawing growth curve, cell viability was evaluated using the Cell Counting Kit 8. The fraction of CD133(+) cell subpopulations was assessed by flow cytometry. We found that Sal inhibits proliferation and decreases PCNA levels as well as the proportion of HCC CD133(+)cell subpopulations in HCC cells. Cell cycle was analyzed using flow cytometry and showed that Sal caused cell cycle arrest of the various HCC cell lines in different phases. Cell apoptosis was evaluated using flow cytometry and Hoechst 33342 staining. Sal induced apoptosis as characterized by an increase in the Bax/Bcl-2 ratio. Several signaling pathways were selected for further mechanistic analyses using real time-PCR and Western blot assays. Compared to control, ß-catenin expression is significantly down-regulated upon Sal addition. The Ca(2+) concentration in HCC cells was examined by flow cytometry and higher Ca(2+) concentrations were observed in Sal treatment groups. The anti-tumor effect of Sal was further verified in vivo using the hepatoma orthotopic tumor model and the data obtained showed that the size of liver tumors in Sal-treated groups decreased compared to controls. Immunohistochemistry and TUNEL staining also demonstrated that Sal inhibits proliferation and induces apoptosis in vivo. Finally, the role of Sal on in vivo Wnt/ß-catenin signaling was evaluated by Western blot and immunohistochemistry. This study demonstrates Sal inhibits proliferation and induces apoptosis of HCC cells in vitro and in vivo and one potential mechanism is inhibition of Wnt/ß-catenin signaling via increased intracellular Ca(2+) levels.