Anti-hepatocellular carcinoma activity of Sorbaria sorbifolia by regulating VEGFR and c-Met/apoptotic pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Sorbaria sorbifolia (SS) is a traditional Chinese medicine (TCM) that has been employed anti-hepatocellular carcinoma (HCC) for over 2000 years; yet, its underlying mechanism is still not fully understood. AIM OF THE STUDY: In this study, we evaluated the anti-HCC effect on the freeze-dried powder of the water extract of SS (FDSS) by inhibiting tumor-induced neovascularization, and promoting apoptosis, and elucidated the underlying mechanisms. MATERIALS AND METHODS: HCC cell lines (HepG2 and Huh7 cells) and HepG2 xenograft tumors in zebrafish were employed as in vivo and in vitro models, respectively, to evaluate the anti- HCC-indued neovascularization and apoptosis. In HCC cell lines, CCK-8 assay, wound-healing assay, transwell assay, cell circle assay, apoptosis assay, transmission electron microscopy, and co-culture assay were performed in vitro; in HepG2 xenograft tumor-zebrafish, tumor growth inhibition assay, hematoxylin and eosin (HE) staining, xenograft tumor-zebrafish apoptosis assay, and HCC-indued neovascularization assay were performed to evaluate the effect of FDSS on biological behavior of tumor, HCC-indued neovascularization, and apoptosis. The expression of VEGFR and c-Met/apoptotic pathway-related proteins was detected by western blotting analysis. Assays for c-Met and VEGFR activation were conducted to assess the impact of FDSS in either agonistic or inhibitory roles on these receptor proteins. RESULTS: The findings from our study revealed that FDSS effectively suppresses the proliferation, migration, and invasion of HepG2 and Huh7 cells, as well as inhibiting tumor growth in the HepG2 xenograft zebrafish model by downregulating the expression of p-Met and p-AKT proteins. FDSS decreased the tumor growth associated with promoting apoptosis, including arresting HepG2 and Huh7 cells cycle at G0/G1phase, increasing apoptotic cell numbers and apoptotic bodies in cancer cells, and increasing the apoptotic fluorescence of xenograft tumor zebrafish by downregulating Bcl-2 proteins and upregulating Bax, caspase-9, and caspase-3 levels. We also found that FDSS can inhibit HCC-induced neovascularization and regulate VEGFR. Using an agonist or inhibitor of c-Met and VEGFR in HepG2 cells, we discovered that FDSS can downregulate c-Met and VEGFR protein expression. CONCLUSION: FDSS exerts an anti-HCC effect by inhibiting HCC-indued neovascularization and pro-apoptosis through the inhibition of the action of VEGFR and c-Met/apoptotic pathway.

Parasitoid-induced changes in metabolic rate and feeding activity of the emerald ash borer (Coleoptera: Buprestidae): implications for biological control.

Parasitoid-host interactions form the foundation of biological control strategies against many agriculture and forest insect pests. The emerald ash borer (EAB), Agrilus planipennis (Coleoptera: Buprestidae), is a serious invasive pest of ash (Fraxinus spp.) trees in North America. Tetrastichus planipennisi (Hymenoptera: Eulophidae) is a gregarious, koinobiont endoparasitoid, attacking late (3rd to 4th) instars of EAB larvae, which feed in the live phloem of ash trunks or branches, making serpentine-like galleries filled with larval frass. In the present study, we tested the hypothesis that T. planipennisi regulates the host metabolism and feeding activity to optimize its offspring development and fitness. We first compared the respiration rate of parasitized and unparasitized host larvae at different times after parasitism, and then measured feeding activity of both parasitized and unparasitized host larvae inside their feeding galleries. Although parasitized host larvae increased metabolic rate and feeding activity in the first few days of parasitism, T. planipennisi parasitism induced an overall reduction of the metabolic rate and decrease in feeding activity of parasitized host larvae over their development period. In addition, there was a negative relationship between feeding activity of parasitized hosts and brood sizes of the parasitoid progeny-i.e., the more parasitoid progeny a host larva received, the less feeding activity the host had. These findings suggest that T. planipennisi has limited ability to optimize its offspring development and fitness through regulations of the host metabolism and feeding activity and its parasitism reduces feeding damage of parasitized EAB larvae to infested ash trees.

Association and interactions between mixed exposure to trace elements and the prevalence of kidney stones: a study of NHANES 2017-2018.

Background: The association between exposure to trace elements mixture and the prevalence of kidney stones and the interactions between elements are unclear. The aim of this study was to explore the association between exposure to trace elements mixture and the prevalence of kidney stones and the interactions between the elements. Methods: A total of 1,244 participants (139 kidney stone formers and 1,105 non-stone former participants) in NHANES 2017-2018 were included. The exposure to trace elements was evaluated by measuring their concentration in urine samples. Three methods, Logistic regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR), were used for analysis. Results: According to the results from qgcomp and BKMR, a negative association was found between exposure to the 13 trace elements and the prevalence of kidney stones [OR = 0.50 (0.32, 0.78)]. Subgroup analysis revealed that Co, As, and iodine in the whole population, Co, As, and Ni in males, and Cs, iodine, and Sb in females, were most strongly associated with kidney stones. Kidney stone was found to be positively correlated with Co and negatively correlated with the other elements. Besides, there were significant interactions between Ni and Pb in the whole population, Co and iodine in males, and Pb and iodine in females. Conclusion: There was a negative association between exposure to the mixture of 13 trace elements and the prevalence of kidney stones.

Exploring the factors influencing the use of health services by people with diabetes in Northwest China: an example from Gansu Province.

BACKGROUND: Diabetes is associated with high morbidity, mortality and quality-of-life impairment in patients. In China, the number of people suffering from diabetes ranks first in the world. Gansu Province is located in northwest China and is an economically underdeveloped region of China. By analyzing the level of health service utilization of people with diabetes in Gansu Province, the degree of equity in health service utilization and its influencing factors were studied to provide scientific data to support the promotion of health equity for people with diabetes and the introduction of relevant policies by relevant authorities. METHODS: A sample of 282 people with diabetes who were 15 years old and above was chosen by multi-stage stratified sampling method. A structured questionnaire survey was conducted via face-to-face interviews. Random forest and logistic regression analysis were used to demonstrate the effects of the explanatory variables on health seeking behaviors from predisposing, enabling and need variables. The concentration index was used to indicate the equity of health service utilization across households of different economic levels. RESULTS: The outpatient rate for the diabetic population surveyed was 92.91%, with 99.87% of urban patients, higher than the 90.39% of rural patients. The average number of hospital days per person was 3.18 days, with 5.03 days per person in urban areas, which was higher than the 2.51 days per person in rural areas. The study showed that the factors most likely to influence patients to seek outpatient services were frequency of taking diabetic medication, whether or not they were contracted to a household doctor, and living environment; the top three factors most likely to influence patients with diabetes to seek inpatient services were number of non-communicable chronic disease, self-assessment of health status, medical insurance. The concentration index for outpatient service utilization and inpatient service utilization were - 0.241 and 0.107, respectively, indicating that outpatient services were concentrated on patients at lower income levels and patients at higher income levels tended to favor inpatient services. CONCLUSION: This study found that the low level of health care resources available to people with diabetes, whose health status is suboptimal, makes it difficult to meet their health needs. Patients' health conditions, comorbidities of people with diabetes, and the level of protection were still important factors that hindered the use of health services. It is necessary to promote the rational use of health services by diabetic patients and further improve the corresponding policies to achieve the goal of chronic disease prevention and control in "Health China 2030".

Factors influencing catastrophic health expenditure of households with people with diabetes in Northwest China-an example from Gansu Province.

BACKGROUND: Diabetes is a chronic non-communicable disease that causes a substantial economic burden on diabetic suffers and their households. The aim of this study was to explore the prevalence, equity, and determinants of catastrophic health expenditure (CHE) among households with people with diabetes in Northwest China. METHODS: A total of 3,000 households were included in the 6th Health services survey in Gansu Province, China of which 270 households with people with diabetes. The equity of CHE was evaluated by concentration curve and concentration index (CI). We adopted the Pareto chart to analyze the main economic intervals of the occurrence of CHE. Finally, we combined the decision tree and logistic model and analyzed the determinants of the occurrence of CHE. RESULTS: The incidence of CHE at 15%, 25% and 40% were 75.19%, 58.89% and 35.19%, respectively. CHE tended to occur in households with a lower economic level, with the phenomenon being more pronounced at Z = 40%. The Pareto chart showed that households in the group with an annual per capita income of 0-740 USD (0-5,000 Chinese Yuan) were most likely to experience CHE. Both decision tree and logistic models suggested that economic level, comorbidities, and small household size were potential risk factors. In addition, the decision tree model also suggested the interaction between the influencing factor of health checks in the past 12 months and the number of chronic diseases. CONCLUSIONS: In summary, Households with people with diabetes were more likely to incur CHE. It is essential to focus on low- and middle-income households with people with diabetes, strengthen the management of patients with diabetes, and provide timely health interventions to reduce the occurrence of chronic comorbidity and the risk of CHE in households.

Associations of urinary and blood cadmium concentrations with all-cause mortality in US adults with chronic kidney disease: a prospective cohort study.

Epidemiological evidence for the relationship between cadmium exposure and mortality in specific chronic kidney disease (CKD) populations remains scarce. We aimed to explore the relationships between cadmium concentrations in urine and blood and all-cause mortality among CKD patients in the USA. This cohort study was composed of 1825 CKD participants from the National Health and Nutrition Examination Survey (NHANES) (1999-2014) who were followed up to December 31, 2015. All-cause mortality was ascertained by matching the National Death Index (NDI) records. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality in relation to urinary and blood cadmium concentrations by Cox regression models. During an average follow-up period of 82 months, 576 CKD participants died. Compared with the lowest quartiles, HRs (95% CIs) for all-cause mortality associated with the fourth weighted quartiles of urinary and blood cadmium concentrations were 1.75 (1.28 to 2.39) and 1.59 (1.17 to 2.15), respectively. Furthermore, the HRs (95% CIs) for all-cause mortality per ln-transformed IQR increment in cadmium concentrations in urine (1.15 µg/g UCr) and blood (0.95 µg/L) were 1.40 (1.21 to 1.63) and 1.22 (1.07 to 1.40), respectively. Linear concentration-response relationships between urinary and blood cadmium concentrations and all-cause mortality were also found. Our findings suggested that increased cadmium concentrations in both urine and blood significantly contributed to enhanced mortality risk in CKD patients, thus highlighting that efforts to reduce cadmium exposure may reduce mortality risk in high-risk populations with CKD.

[Influencing factors for natural populations of Lycorma delicatula in different habitats]. / ä¸åŒæ –å¢ƒæ¡ä»¶ä¸‹æ–‘è¡£èœ¡è‰è‡ªç„¶ç§ç¾¤çš„å½±å“å› å­.

To explore the differences between growth and population dynamics of natural Lycorma delicatula in the plantations and semi-natural forests, the susceptible stages and major suppression factors were determined to provide basis for the prediction and controlling the pest. The development duration and life table of L. delicatula in different habitats were established by using tracking method. The index of exclusion effect for lethal factors and the K-value in each development stage were calculated. The population trends were analyzed through the survival curve and key drivers of population change. The results showed that the development duration of L. delicatula in the plantation habitat and semi-natural habitat was significantly different, with thelatter being 25.7 d longer than the former. There were significant differences in the development duration of 1st-3rd-instars nymphs and pre-oviposition period of adults between these two habitats, but no significant difference in the 4th-instar nymphs. The total mortality rate in the plantation habitat and semi-natural habitat was 83.6% and 98.6%, respectively. The index of population trend in the plantation habitat was significantly higher than that in the semi-natural habitat. The population of L. delicatula increased sharply in the plantation habitat, but showed a decline trend in the semi-natural habitat. All of the survival curves of L. delicatula were Deevey-Ⅲ type, and the EIPCs of the "parasitic natural enemies" in egg stage were the highest in both habitats as 1.3 and 1.6, and the total K values were 0.2 and 0.3, respectively. The regression slopes of K-value of natural enemies were the highest (both 0.6). These findings revealed that the semi-natural habitat played an important role in the natural regulation of L. delicatula.

[Evaluation of Air Pollution Characteristics and Air Quality Improvement Effect in Beijing and Chengdu].

In recent years, China's air quality has been improving, and the concentration of atmospheric particulate matter has decreased significantly. In this study, the pollution characteristics and trends of two typical representative cities (Beijing and Chengdu) were analyzed. The geographical locations, pollution emissions, and meteorological diffusion conditions of the two cities were compared, to evaluate the relative contribution of meteorological conditions and pollution reduction regulations in decreasing fine particulate matter (PM2.5) concentrations. The results showed that the number of heavily polluted days and pollution episodes in Beijing and Chengdu decreased significantly from 2013 to 2018, and the concentration of SO2 and PM2.5 decreased substantially. Compared to 2013, SO2 concentration in Beijing and Chengdu has decreased by 77.8% and 70.9%, whereas PM2.5 concentration has decreased by 42.7% and 48.5%, respectively. The largest reduction appeared in winter, when PM2.5 decreased at an annual rate of 13.5 µg ·m-3 for Beijing and 14.1 µg ·m-3 for Chengdu. During the study period, the wind speed in Chengdu was less than that in Beijing, temperature was approximately 3℃ higher, and static wind in winter was more frequent. A significantly lower mixed-layer height, atmospheric capacity index, and ventilation coefficient in Chengdu resulted in more unfavorable atmospheric diffusion conditions. The static and stable weather index and the environmental meteorological index (EMI) also showed that the atmospheric diffusion conditions were better in Beijing than in Chengdu. The EMI of the two cities showed a decreasing trend during the study period, and the decline in EMI in Chengdu was the most significant in 2018, indicating an evident improvement in meteorological conditions. In 2018, emission reductions are estimated to have contributed 33.5% and 24% to the decrease in PM2.5 in Beijing and Chengdu, respectively, and meteorological conditions contributed 7.2% and 11.1% to the reduction in these two cities. In winter, emission reductions respectively contributed 31.7% and 32.5% to reduction in Beijing and Chengdu, while meteorological conditions made a larger contribution.

HLA-E-restricted HIV-1-specific CD8+ T cell responses in natural infection.

CD8+ T cell responses restricted by MHC-E, a nonclassical MHC molecule, have been associated with protection in an SIV/rhesus macaque model. The biological relevance of HLA-E-restricted CD8+ T cell responses in HIV infection, however, remains unknown. In this study, CD8+ T cells responding to HIV-1 Gag peptides presented by HLA-E were analyzed. Using in vitro assays, we observed HLA-E-restricted T cell responses to what we believe to be a newly identified subdominant Gag-KL9 as well as a well-described immunodominant Gag-KF11 epitope in T cell lines derived from chronically HIV-infected patients and also primed from healthy donors. Blocking of the HLA-E/KF11 binding by the B7 signal peptide resulted in decreased CD8+ T cell responses. KF11 presented via HLA-E in HIV-infected cells was recognized by antigen-specific CD8+ T cells. Importantly, bulk CD8+ T cells obtained from HIV-infected individuals recognized infected cells via HLA-E presentation. Ex vivo analyses at the epitope level showed a higher responder frequency of HLA-E-restricted responses to KF11 compared with KL9. Taken together, our findings of HLA-E-restricted HIV-specific immune responses offer intriguing and possibly paradigm-shifting insights into factors that contribute to the immunodominance of CD8+ T cell responses in HIV infection.

Relationship between carotid intraplaque neovascularization and haemoglobin A1c in diabetic patients.

INTRODUCTION: We aimed to evaluate the characteristics of carotid artery plaques and the relationship between intraplaque neovascularization (IPN) and hemoglobin A1c (HbA1c) in patients of <60 years old with diabetes mellitus (DM) by comparison with diabetes ≥60 years of age. METHODS: One-hundred-and-one patients with DM were studied into two groups: those <60 and those ≥60 years of age. All the patients underwent standard carotid ultrasonography and contrast-enhanced ultrasonography, which we used to evaluate IPN. RESULTS: Diabetic complications were present in 41 of 50 patients (82 %) in the <60-year-old group, of whom 17 (34 %) had diabetes-related vascular complications. Of the 47 plaques in the <60-year-old group, six (13 %) had IPN Grade 0, 16 (34 %) had IPN Grade 1, and 25 (53 %) had IPN Grade 2. The AUC and RAUC of the plaque in the <60-year-old group were significantly higher than those of the ≥60-year-old group (P = 0.012 and 0.031, respectively). There were also differences in the AUC, RAUC and semi-quantitative grades between patients with and without diabetic macrovasculopathy and diabetic peripheral artery disease (all P < 0.05). The AUC, RAUC and semi-quantitative grading of IPN positively correlated with blood glucose and HbA1c (P < 0.05). CONCLUSION: IPN is more common in DM patients who are younger, and have higher blood glucose and HbA1c concentrations, and these plaques are more vulnerable.

Carotid Intraplaque Neovascularization Predicts Ischemic Stroke Recurrence in Patients with Carotid Atherosclerosis.

INTRODUCTION: This study aimed to examine whether intraplaque neovascularization (IPN) of carotid plaques, as characterized by contrast-enhanced ultrasound (CEUS), is associated with ischemic stroke recurrence in patients with carotid atherosclerosis. METHODS: We conducted a prospective study of consecutive patients with a recent stroke and at least one atherosclerotic plaque in the carotid artery on the side consistent with symptoms. All patients underwent CEUS after their first admission. IPN was graded on the basis of the presence and location of microbubbles within each plaque. RESULTS: We eventually included 155 patients, all of whom underwent IPN analysis. After a follow-up of 24 months, we recorded 25 (16.1%) stroke recurrences in the whole population. All the recurrences occurred in patients presenting IPN. There was significant difference in the IPN between the 2 groups (p = 0.002). In the final Cox proportional-hazards multivariable models, IPN of grade 2 was independently associated with the risk of stroke recurrence (HR = 4.535; 95% CI: 1.892-10.870; p = 0.001). This association remained after adjusting for the degree of carotid stenosis (HR = 3.491; 95% CI: 1.410-8.646; p = 0.007). CONCLUSIONS: IPN was an independent predictor of stroke recurrence in patients with a recent ischemic stroke and carotid atherosclerosis. In predicting stroke recurrence, IPN may be an earlier indicator than carotid stenosis and may help stratify the risk of stroke recurrence.

The impact of urbanization and consumption patterns on China's black carbon emissions based on input-output analysis and structural decomposition analysis.

Urbanization in China has dramatically increased from 39.10 in 2002 to 58.52% in 2017. Studies have discussed the impacts of urbanization and its corresponding changes in consumption patterns on carbon dioxide emissions; however, little is known about their impacts on black carbon (BC). Therefore, we collected data on the BC emissions of various sectors to calculate the consumption-based BC emissions in China, and we used an input-output analysis (IOA) and structural decomposition analysis (SDA) to explore the impacts of urbanization and changes in consumption patterns on BC emissions from 2002 to 2017, focusing on sectoral BC emissions. The total BC emissions of various sectors first increased and then decreased. BC emissions increased from 1083.47 in 2002 to 2550.83 Gg in 2012. They were then reduced to 2478.63 Gg in 2017. Additionally, with the rise in the urbanization rate, household consumption BC emissions increased from 446.18 in 2002 to 1080.12 Gg in 2017. Urban consumption, rural consumption, and BC emission intensity were the three main contributing factors to household consumption BC emission changes. Transport, storage, postal, and telecommunications services (TSP); farming, forestry, animal husbandry, and fishery (FFA); and residential and other industries (RES) contributed the most to the urbanization-related BC emission increase. In particular, the TSP sector contributed the most to the BC emission increase because of the increasing TSP needs related to urbanization. Therefore, it is necessary to formulate mitigation policies for the TSP sector.

Carotid intraplaque neovascularization predicts atherosclerotic renal artery stenosis in patients with carotid artery stenosis.

BACKGROUND AND AIMS: This study aimed to examine whether intraplaque neovascularization (IPN) of carotid plaques, as characterized by contrast-enhanced ultrasound (CEUS), is associated with atherosclerotic renal artery stenosis (ARAS) in patients with normal kidney function. METHODS AND RESULTS: We investigated carotid IPN using CEUS in 198 consecutive patients with normal kidney function with and without ARAS. IPN was graded on the basis of the presence and location of microbubbles within each plaque (0, no visible microbubbles in the plaque; 1, moderate microbubbles confined to the shoulder and/or adventitial side of the plaque; and 2, extensive microbubbles throughout the plaque). The grades of each plaque were averaged to obtain an overall score per patient. ARAS was determined angiographically. We found that a higher CEUS-assessed carotid IPN score was associated with ARAS (Odd Ratio, OR: 7.281; 95% Confidence Interval, 95% CI: 3.246-16.336; P < 0.001). Furthermore, an IPN score >1.75 predicted severe stenosis with a sensitivity of 81% and specificity of 58%. Compared with using the IPN score alone, the addition of the homocysteine (HCY) cutoff value (>22.5 mmol/L) resulted in a stronger predictive value (Area Under Curve, AUC: 0.893 vs 0.834; P < 0.001) for severe ARAS. CONCLUSION: Carotid plaque neovascularization combined with HCY levels is predictive of severe ARAS in patients with normal kidney function. CEUS-assessed carotid IPN is clinically useful for stratification of ARAS in patients with normal kidney function.

CHD is Associated With Higher Grades of NAFLD Predicted by Liver Stiffness.

BACKGROUND AND AIM: Accumulating clinical and epidemiologic evidence indicates that nonalcoholic fatty liver disease (NAFLD) is not only associated with liver-related morbidity and mortality, but also with a greater risk of coronary heart disease (CHD). However, there is currently no diagnostic parameter for NAFLD that has been determined to reliably indicate the presence of CHD as a co-morbidity. We evaluated the liver stiffness and visceral fat thickness of NAFLD patients ultrasonographically to explore the relationship between liver stiffness, visceral fat thickness, and CHD, aiming to find explore the relationship between the liver stiffness and CHD. METHODS: We enrolled 120 consecutive patients who had been initially diagnosed with CHD on the basis of their symptoms. All patients underwent coronary angiography or computed tomography angiography, and were classified into a CHD group and a non-CHD group on the basis of the results. All patients underwent liver ultrasonography, shear-wave elastography, and visceral fat thickness measurement. RESULTS: NAFLD and visceral fat thickness were significantly positively correlated with CHD and Gensini score (P<0.001). Multivariate regression showed that age, male, cholesterol, liver stiffness, and visceral fat thickness were determinants of CHD. Age, cholesterol, liver stiffness, and visceral fat thickness cut-off points for the prediction of CHD were above 50 years old [area under the curve (AUC): 0.678; sensitivity, 87%; specificity, 42.6%], >3.76 mmol/L (AUC: 0.687; sensitivity, 68.4%; specificity, 64.8%), >6.1 kPa (AUC: 0.798; sensitivity, 50%; specificity, 92.6%), and >7.41 cm (AUC: 0.694; sensitivity, 52.6%; specificity, 87%), respectively. Compared with the use of age, gender, and cholesterol (model 1), the addition of the liver stiffness cut-off to model 1 resulted in a stronger predictive value (P=0.005). CONCLUSIONS: High-grade NAFLD is more present in symptomatic CHD. The higher degree of liver stiffness in patients with NAFLD, the higher risk of CHD in these NAFLD patients.

Development and External Validation of a Novel Immune Checkpoint-Related Gene Signature for Prediction of Overall Survival in Hepatocellular Carcinoma.

Objective: The purpose of this study was to develop and validate a novel immune checkpoint-related gene signature for prediction of overall survival (OS) in hepatocellular carcinoma (HCC). Methods: mRNA expression profiles and clinical follow-up information were obtained in the International Cancer Genome Consortium database. An external dataset from The Cancer Genome Atlas (TCGA) Liver Hepatocellular Carcinoma database was used to validate the results. The univariate and multivariate Cox regression analyses were performed based on the differentially expressed genes. We generated a four-mRNA signature to predict patient survival. Furthermore, the reliability and validity were validated in TCGA cohort. An integrated bioinformatics approach was performed to evaluate its diagnostic and prognostic value. Results: A four-gene (epidermal growth factor, mutated in colorectal cancer, mitogen-activated protein kinase kinase 2, and NRAS proto-oncogene, GTPase) signature was built to classify patients into two risk groups using a risk score with different OS in two cohorts (all P < 0.0001). Multivariate regression analysis demonstrated the signature was an independent predictor of HCC. Furthermore, the signature presented an excellent diagnostic power in differentiating HCC and adjacent tissues. Immune cell infiltration analysis revealed that the signature was associated with a number of immune cell subtypes. Conclusion: We identified a four-immune checkpoint-related gene signature as a robust biomarker with great potential for clinical application in risk stratification and OS prediction in HCC patients and could be a potential indicator of immunotherapy in HCC. The diagnostic signature had been validated to accurately distinguish HCC from adjacent tissues.

Association between Nonalcoholic Fatty Liver and Gensini Score in Patients with Coronary Heart Disease: A Cross-Sectional Study.

INTRODUCTION: Obesity is one of the important risk factors of coronary heart disease (CHD). Nonalcoholic fatty liver disease (NAFLD) is always accompanied by obesity. Therefore, this study was designed to elucidate the relationship between NAFLD and CHD in obese and nonobese populations. METHODS: We conducted a cross-sectional study of 454 Chinese patients diagnosed with CHD. Patients were grouped into non-NAFLD + nonobese, non-NAFLD + obese, NAFLD + nonobese, and NAFLD + obese based on the presence or absence of both NAFLD and obesity. RESULTS: The mean Gensini score was significantly higher in patients with fatty liver compared to those without. Logistic regression analysis found that fatty liver, uric acid, and blood glucose levels were risk factors for a high Gensini score. CONCLUSIONS: Irrespective of the presence of obesity, NAFLD is a risk factor for CHD, and the clinical effect of nonobese fatty liver (especially in women) should be carefully considered.

[Isoliquiritigenin can inhibit migration and invasion of human glioma stem cells by down-regulating matrix metalloproteinases].

OBJECTIVE: To investigate the effects of isoliquiritigenin on the migration and invasion of human glioma stem cells and the underlying mechanism. METHODS: The stem cell markers CD133 and Nestin in SHG44 human glioma stem cells were examined with immunofluorescence microscopy. The migration and invasion ability of glioma stem cells was determined by transwell method. The mRNA and protein expression of matrix metalloproteinase (MMP)-2 and MMP-9 were detected by real-time RT-PCR and Western blot, respectively. RESULTS: CD133 and Nestin were positive in SHG44 cells. The number of migrated cells in SHG44 cells treated with 20 and 80 µmol/L isoliquiritigenin for 48 h were significantly lower than that in control group (76±5 and 42±4 vs. 85±6, all P<0.01), and the number of migrated cells in 80 µmol/L isoliquiritigenin group was lower than that in 20 µmol/L isoliquiritigenin group (P<0.01). The numbers of cells crossing through membrane in 20 and 80 µmol/L isoliquiritigenin groups were 190±13 and 130±9, respectively, which were significantly lower than that in control group (230±14, all P<0.01), and the number of crossed cells in the 80 µmol/L isoliquiritigenin group was lower than that in 20 µmol/L isoliquiritigenin group (P<0.01). The mRNA and protein expression levels of MMP-2 and MMP-9 were decreased compared with control group (P<0.05 or P<0.01), and the expression levels in 80 µmol/L isoliquiritigenin group were lower than those in 20 µmol/L isoliquiritigenin group (P<0.05 or P<0.01). CONCLUSIONS: Isoliquiritigenin exhibits antitumor effects on glioma stem cells by inhibiting cell migration and invasion, which may be related to the down-regulation of MMP-2 and MMP-9.

Carotid Plaque Stiffness Measured with Supersonic Shear Imaging and Its Correlation with Serum Homocysteine Level in Ischemic Stroke Patients.

Objective: To ascertain the feasibility of using shear wave velocity (SWV) in assessing the stiffness of carotid plaque by supersonic shear imaging (SSI) and explore preliminary clinical value for such evaluation. Materials and Methods: Supersonic shear imaging was performed in 142 patients with ischemic stroke, including 76 males and 66 females with mean age of 66 years (range, 45-80 years). The maximum, minimum, and mean values of SWV were measured for 129 carotid plaques. SWVs were compared between echolucent and echogenic plaques. Correlations between SWVs and serum homocysteine levels were investigated. Based on neurological symptom, the surrogate marker of vulnerable plaque (VP), binary logistic regression was performed and area under curve (AUC) of homocysteine only and homocysteine combing SWVmean was calculated respectively. Results: Echogenic plaques (n = 51) had higher SWVs than echolucent ones (n = 78) (SWVmin 3.91 [3.24-4.17] m/s vs. 1.51 [1.04-1.94] m/s; SWVmean, 4.29 [3.98-4.57] m/s vs. 2.09 [1.69-2.41] m/s; SWVmax, 4.67 [4.33-4.86] m/s vs. 2.62 [2.32-3.31] m/s all p values < 0.01). Pearson correlation analysis showed that stiffness of plaques was negatively correlated with homocysteine level. R values for SWVmin, SWVmean, and SWVmax were -0.205, -0.213, and -0.199, respectively. Binary logistic regression analysis showed that sex (p = 0.008), low-density lipoprotein (p = 0.015), triglycerides (p = 0.011), SWVmean (p = 0.004), and hyper-homocysteinemia (p = 0.010) were significantly associated with symptomatic ischemic stroke. Receiver operating characteristic curves revealed that SWVmean combing serum homocysteine level (AUC = 0.67) presented better diagnostic value than serum homocysteine only (AUC = 0.60) for symptomatic ischemic stroke. Conclusion: Supersonic shear imaging could be used to quantitatively evaluate stiffness of both echolucent and echogenic carotid plaques. More importantly, SWVs of plaques were not only correlated to serum homocysteine level, but also associated with symptomatic ischemic stroke, suggesting that SSI might be useful for understanding more about VP.

Isoliquiritigenin inhibits the proliferation and induces the differentiation of human glioma stem cells.

Glioma stem cells (GSCs) have been proven to be resistant to various therapeutic strategies, such as temozolomide chemotherapy and radiotherapy, leading to glioma recurrence. Isoliquiritigenin (ISL), a menber of the flavonoids isolated from liquorice has been found to be a potent stimulator of cell differentiation and has potential application for treating various types of cancer including human brain glioma. However, the antitumor activity of ISL on GSCs and the signaling pathway underlying its therapeutic effects are poorly understood. In the present study, GSCs were isolated from SHG44 human glioma cells by serum-free culture and treated with ISL or DAPT (a Notch/γ-secretase inhibitor). It was found that ISL dose-dependently inhibited GSC growth after 72 h of treatment and decreased the formation of tumor spheres. Meanwhile, GSCs differentiated into astrocytes and neurons. Furthermore, these therapeutic effects were accompanied by downregulation of Notch1 and Hes1 at the protein and mRNA levels. Taken together, our results demonstrated that ISL exhibits antitumor effects on GSCs by inhibiting proliferation and inducing differentiation. The therapeutic effect may be related to downregulation of the Notch1 signaling pathway. Application of ISL presents potential benefits for the treatment of human brain glioma.