Detection of minimal hepatic encephalopathy in patients with cirrhosis based on the Stroop-CN model (NCRCID-CHESS 2106): a prospective multicenter study.

Minimal hepatic encephalopathy (MHE) has a substantial impact on the clinical outcomes and quality of life (QOL) of patients with cirrhosis. However, timely diagnosis and intervention are challenging due to sophisticated diagnostic methods. In this study, 673 healthy controls and 905 patients with cirrhosis were screened, and 660 healthy controls and 757 patients with cirrhosis, divided into the test (292 patients) and validation (465 patients) cohort, were analyzed after screening. A diagnostic model of the Stroop test (Stroop-CN) was constructed by multivariate linear regression based on the results of healthy controls. The prevalence of MHE and the comparison results with psychometric hepatic encephalopathy score through the Stroop-CN model were stable in the test and validation cohorts. Moreover, the prevalence of MHE remained significantly higher in patients with worse disease conditions marked as high Child-Pugh grades and the Model for End-stage Liver Disease and Sodium (MELD-Na) scores in the test and validation cohort. The EuroQol 5-D questionnaire revealed that patients with MHE had a worse QOL than those without MHE both in the test and validation cohort. In conclusion, an easy and practical Stroop-CN model for MHE diagnosis based on the EncephalApp is established. It is found that a considerable number of Chinese patients with cirrhosis experience MHE, which significantly impacts their QOL.

Protective Effects Of Astragalus Polysaccharides On Oxidative Stress In High Glucose-Induced Or SOD2-Silenced H9C2 Cells Based On PCR Array Analysis.

BACKGROUND: Oxidative stress in cardiac myocytes is an important pathogenesis of diabetic cardiomyopathy (DCM). Previously, we reported that astragalus polysaccharide (APS) has protective effects against the oxidative stress of DCM. This study aimed to determine the effect of APS on the oxidative stress induced by hyperglycemia in H9C2 cells. METHODS: Rat H9C2 cells were cultured in vitro and randomly divided into the control group, HG group, APS-HG group, siRNASOD2 group, and APS-siRNASOD2 group. The cellular ultrastructure was measured by transmission electron microscopy. Cell apoptosis was examined by TUNEL staining. Levels of reactive oxygen species (ROS) were detected by a quantitative fluorescence assay (DHE). 8-OH-dG and nitrotyrosine, the indicators of oxidative stress injury, were detected by immunohistochemistry. A PCR array was used to evaluate the expression levels of 84 oxidative stress genes in cultured cells, and the PCR array results were partially verified by Western blot. RESULTS: APS treatment protected the H9C2 cell ultrastructure, reduced the level of cell apoptosis, inhibited cellular ROS production, and reduced the levels of oxidative stress injury indicators 8-OH-dG and nitrotyrosine in high glucose-induced or SOD2-silenced H9C2 cells. It also altered oxidative stress-related genes at the mRNA and protein levels. CONCLUSION: APS may improve antioxidant capacity and inhibit oxidative stress injury in high glucose induced H9C2 cells.

Effect of Astragalus Polysaccharides on Cardiac Dysfunction in db/db Mice with Respect to Oxidant Stress.

OBJECTIVE: Oxidant stress plays an important role in the development of diabetic cardiomyopathy. Previously we reported that Astragalus polysaccharides (APS) rescued heart dysfunction and cardinal pathological abnormalities in diabetic mice. In the current study, we determined whether the effect of APS on diabetic cardiomyopathy was associated with its impact on oxidant stress. METHODS: Db/db diabetic mice were employed and administered with APS. The hematodynamics, cardiac ultra-structure, apoptosis, and ROS formation of myocardium were assessed. The cardiac protein expression of apoptosis target genes (Bax, Bcl-2, and caspase-3) and oxidation target genes (Gpx, SOD2, t/p-JNK, catalase, t/p-p38 MAPK, and t/p-ERK) were evaluated, respectively. RESULTS: APS therapy improved hematodynamics and cardinal ultra-structure with reduced apoptosis and ROS formation in db/db hearts. In addition, APS therapy inhibited the protein expression of apoptosis target genes (Bax, Bcl-2, and caspase-3) and regulated the protein expression of oxidation target genes (enhancing Gpx, SOD2, and catalase, while reducing t/p-JNK, t/p-ERK, and t/p-p38 MAPK) in db/db hearts. CONCLUSION: Our findings suggest that APS has benefits in diabetic cardiomyopathy, which may be partly associated with its impact on cardiac oxidant stress.

Astragalus polysaccharides inhibit oxidation in high glucose-challenged or SOD2-silenced H9C2 cells.

INTRODUCTION: Oxidative stress plays an important role in the development of diabetic cardio-myopathy (DCM). Previously, we reported that Astragalus polysaccharides (APS) improved DCM by inhibition of cardiac oxidative stress. In this study, we evaluated the beneficial effect of APS on high glucose-induced oxidative stress in cardiomyocytes in vitro. MATERIALS AND METHODS: H9C2 cells were cultured in the presence of high concentration of glucose or transfected with siRNASOD2, followed by APS treatment. The cellular mitochondrial ultrastructure was observed using a transmission electron microscope. Cell apoptosis was detected using hairpin oligonucleotide probes and quantified by flow cytometry analysis. Superoxide production was determined by immunohistochemistry using the fluorescent dye dihydroethidium (DHE). Nitrotyrosine and 8-OH-dG antibodies were employed to detect oxidative damage to cytoplasmic proteins and oxidative stress in the nuclei, respectively. Superoxide dismutase (SOD) activity was measured utilizing the SOD Assay Kit, and SOD protein levels were analyzed by Western blotting. RESULTS: APS treatment protected cellular mitochondrial ultrastructure, reduced cell apoptosis (hairpin-1), inhibited cellular superoxide production (DHE), and reduced oxidative damage to cytoplasmic proteins (nitrotyrosine) and oxidative stress in the nuclei (8-OH-dG) in high glucose-induced and/or SOD2-silenced H9C2 cells, together with induction of SOD2 enzyme activity and increase of protein levels. CONCLUSION: Our findings indicated the beneficial effect of APS on high glucose-challenged H9C2 cells, which was associated with inhibition of oxidative stress in vitro.

Astragalus polysaccharides protect cardiac stem and progenitor cells by the inhibition of oxidative stress-mediated apoptosis in diabetic hearts.

INTRODUCTION: Diabetic cardiomyopathy is characterized by an imbalance between myocyte death and regeneration mediated by the progressive loss of cardiac stem and progenitor cells (CSPCs) by apoptosis and necrosis due to the activation of oxidative stress with diabetes. In this study, we evaluated the beneficial effect of astragalus polysaccharides (APS) therapy on the protection of CSPCs through its antioxidative capacity in diabetic hearts. MATERIALS AND METHODS: Streptozotocin (STZ)-induced diabetic mice and heterozygous (SOD2+/-) knockout mice were employed and administered with APS. Ventricular CSPCs were isolated for oxidative evaluation. The abundance, apoptosis and proliferation, reactive oxygen species (ROS) formation, oxidative damage, and SOD2 protein levels and activities were evaluated in ventricular CSPCs. RESULTS: We confirmed that APS increased the CSPC abundance, reduced the apoptosis of CSPCs, and enhanced the proliferation of CSPCs in both STZ-induced diabetic mice and nondiabetic SOD2+/- mice. In addition, therapy of APS enhanced SOD2 protein levels and enzyme activities, and inhibited ROS formation and oxidative damage of CSPCs from both STZ-induced diabetic mice and nondiabetic SOD2+/- mice. CONCLUSION: Our findings demonstrated the positive effect of APS on the rescue of CSPC preservation in diabetes, dependent on the inhibition of oxidative stress-mediated apoptosis.

Incidence of Pituitary Apoplexy and Its Risk Factors in Chinese People: A Database Study of Patients with Pituitary Adenoma.

BACKGROUND: There are few studies of the incidence and clinical characteristics of pituitary apoplexy (PA) in pituitary adenoma patients, and the findings have been inconsistent. OBJECTIVE: The aim of the study was to retrospectively assess the incidence, clinical presentation, surgical management and postoperative complications of PA in pituitary adenoma patients. METHODS: A database was specifically designed to collect clinical, therapeutic, prognostic and histological information about pituitary adenoma patients. Using multivariate logistic regression, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to identify associated factors. RESULTS: A total of 2021 pituitary adenoma patients were recruited. 97 (4.8%) patients had PA. The incidence of PA was 10.11% in patients with pituitary macroadenoma, and 0.36% in patients with microadenoma. Variables for the logistic regression model independently associated with PA were sex (male vs. female, OR = 2.54, 95% CI: 1.59~4.07), tumor type (negative staining vs. positive staining, OR = 2.04, 95% CI: 1.29~3.23), and tumor size (macroadenoma vs. microadenoma, OR = 26.46, 95% CI = 9.66~72.46). Headache, visual deterioration, and vomiting were the most common symptoms in patients with pituitary adenoma. Patients with and without PA had similar frequency of visual deterioration, head trauma, acromegalic appearance, galactorrhoea, cold intolerance and Cushingoid appearance, but headache, vomiting, ptosis, diplopia, fever and blindness were significantly more common in patients with PA. Pearson Chi-Square tests revealed a significant difference in surgical approach between patients with and without PA (95.88% vs. 85.57%, P = 0.01). CONCLUSION: Our findings suggest that PA is not a rare event. Male sex, non-functioning tumor, and macroadenoma are associated with an increased risk of PA. Compared with pituitary adenoma patients without PA, patients with PA have more severe symptoms.

Astragalus polysaccharides repress myocardial lipotoxicity in a PPARalpha-dependent manner in vitro and in vivo in mice.

BACKGROUND: The role of peroxisome proliferator-activated receptor alpha (PPARα) in the development of myocardial lipotoxicity is widely observed in diabetic disorders. Thus, we investigated if treatment of Astragalus polysaccharides modulates lipotoxic cardiomyopathy both in vivo and in vitro through PPARα mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: The effects of Astragalus polysaccharides (APS) on PPARα target gene expression and protein levels were tested in vitro and in vivo, including in mice with PPARα cardiac-restricted overexpression [myosin heavy chain (MHC)-PPARα] and in H9c2 embryonic rat cardiomyocytes with or without PPARα agonist. Echocardiographic studies, analyses of myocardial triglyceride and cardiac fuel utilization analyses were also performed in MHC-PPARα mice. Treatment with APS prevented myocardial triglyceride accumulation and cardiac dysfunction in the MHC-PPARα mice, with the normalization of energy metabolic derangements in hearts including reduced free fatty acids utilization and increased glucose uptake. Consistently, both in the MHC-PPARα hearts and H9c2 cardiomyocytes with PPARα agonist, the activation of PPARα gene regulatory pathway involved in FFA-oxidation was down-regulated by APS treatment, while the suppression of PPARα target genes involved in glucose uptake and oxidation was normalized by APS administration. CONCLUSIONS: Therapy with APS could prevent the development of lipotoxic cardiomyopathy through a mechanism mainly dependent on the cardiac PPARα-mediated regulatory pathways.

Therapy with Astragalus polysaccharides rescues lipotoxic cardiomyopathy in MHC-PPARα mice.

Obesity-related diabetes mellitus leads to lipotoxic cardiomyopathy resulting in a form of cardiac dysfunction. Mice with heart-specific overexpression of peroxisome proliferator-activated receptor (PPAR) α showed a metabolic and cardiomyopathic phenotype similar to the diabetic heart. To define the role of Astragalus Polysaccharides (APS) treatment for PPARα-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy, myosin heavy chain [MHC]-PPARα mice with high-fat diet were administrated with APS or vehicle for 16 weeks. The APS treatment prevented myocardial long-chain triglyceride accumulation, ultrastructure abnormality in cardiac myocytes and cardiac dysfunction in the MHC-PPARα mice, which was associated with reduced free fatty acids (FFA) utilization and increased glucose uptake and oxidation in hearts by APS treatment. Consistent with the metabolic changes, activation of PPARα gene regulatory pathway involved in FFA-oxidation in the MHC-PPARα heart was down-regulated by APS treatment, while suppression of PPARα target genes involved in glucose uptake and oxidation in the MHC-PPARα hearts was normalized by APS administration. We conclude that therapy with APS might lead to the inhibition of PPARα-mediate lipotoxicity in the pathogenesis of diabetic cardiomyopathy.

The critical role of Astragalus polysaccharides for the improvement of PPARα [ correction of PPRAα]-mediated lipotoxicity in diabetic cardiomyopathy.

BACKGROUND: Obesity-related diabetes mellitus leads to increased myocardial uptake and oxidation of fatty acids, resulting in a form of cardiac dysfunction referred to as lipotoxic cardiomyopathy. We have shown previously that Astragalus polysaccharides (APS) administration was sufficient to improve the systemic metabolic disorder and cardiac dysfunction in diabetic models. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the precise role of APS therapy in the pathogenesis of myocardial lipotoxity in diabetes, db/db diabetic mice and myosin heavy chain (MHC)- peroxisome proliferator-activated receptor (PPAR) α mice were characterized and administrated with or without APS with C57 wide- type mice as normal control. APS treatment strikingly improved the myocyte triacylglyceride accumulation and cardiac dysfunction in both db/db mice and MHC-PPARα mice, with the normalization of energy metabolic derangements in both db/db diabetic hearts and MHC-PPARα hearts. Consistently, the activation of PPARα target genes involved in myocardial fatty acid uptake and oxidation in both db/db diabetic hearts and MHC-PPARα hearts was reciprocally repressed by APS administration, while PPARα-mediated suppression of genes involved in glucose utilization of both diabetic hearts and MHC-PPARα hearts was reversed by treatment with APS. CONCLUSIONS: We conclude that APS therapy could prevent the development of diabetic cardiomyopathy through a mechanism mainly dependent on the cardiac PPARα-mediated regulatory pathways.

[Study of the quasispecies dynamics of serum hepatitis B virus in a patient with acute exacerbations of chronic hepatitis B].

OBJECTIVES: To investigate the quasispecies dynamics of hepatitis B virus (HBV) during the course of exacerbation and resolution of chronic hepatitis B in a patients. METHODS: Five serum samples were collected from a patient with two episodes of exacerbation and resolution of chronic hepatitis B. A method of PCR-TA cloning-conformation sensitive gel electrophoresis (CSGE)-sequencing was performed to study the dynamic changes of HBV quasispecies in basal core promoter (BCP), precore and core regions of HBV genome. RESULTS: Quasispecies complexity was 10 and 12 at the points of exacerbations, and 14 and 17 at the points of resolutions (t = 3.133, P < 0.05). Ratio of dominant quasispecies in HBV population was high (42.4% and 51.5%) during exacerbations and low (30.3% and 21.2%) during resolutions (t = 3.295, P < 0.05). All dominant quasispecies, except the one during the second resolution, carried core P5T, L60V, S155T, and precore G1896A mutations. CONCLUSION: The composition of HBV quasispecies changes due to the change of host immune status, and immune pressure might lead to the selection of immune escape mutants.