Effects of atorvastatin and rosuvastatin on blood lipids, platelet aggregation rate and inflammatory factors in patients with cerebral infarction

Purpose: To investigate the effects of atorvastatin and rosuvastatin on blood lipids, platelet aggregation rate (PAR) and inflammatory factors in patients with cerebral infarction.Methods: Patients (n = 120) with cerebral infarction treated in Feng Hua People's Hospital, Jiang Feng Hua, China from January 2014 to October 2016 were randomly divided into control group (clopidogrel combined with atorvastatin, 60 cases) and observation group (clopidogrel combined with rosuvastatin, 60 cases). Blood lipids, PAR, inflammatory factors and carotid atherosclerotic plaque were recorded and compared.Results: Following treatment, total cholesterol (TC), triglycerides (TG) and low  density lipoprotein cholesterol (LDL-C) in the observation group were significantly lower (p < 0.05) than in the control group, while high density lipoprotein cholesterol (HDL-C) was significantly higher (p < 0.05). C-reactive protein (CRP), tumor necrosis factor-α (IL-6) and interleukin-6 (IL-6) were significantly decreased in the two groups after treatment (p < 0.05). Plaque area, intima-media thickness (IMT) and number of plaques in the two groups were significantly lower after treatment than before treatment (p < 0.05). Plaque area, IMT and number of plaques in the observation group were significantly lower than those in the control group (p < 0.05).Conclusion: Atorvastatin and rosuvastatin have no significant effect on the  antiplatelet function of clopidogrel, but rosuvastatin shows better control of blood lipids, carotid atherosclerosis and inflammatory factors.Keywords: Atorvastatin, Rosuvastatin, Cerebral infarction, Blood lipids, Platelet aggregation rate, Inflammatory factor

Effectiveness of erythropoietin supplementation against chronic heart failure with anemia, and its effect on serum hypersensitive C reaction protein, homocysteic acid and Btype natriuretic peptide

Purpose: To study the effectiveness of exogenous erythropoietin (EPO) against chronic heart failure (CHF) with anemia, and its effect on serum hypersensitive C reaction protein (hs-CRP), homocysteic acid (Hcy ) and B-type natriuretic peptide (BNP).Methods: A total of 136 patients suffering from CHF with anemia from June 2015 to June 2017 were randomly divided into observation group (n = 68) and control group (n = 68). On the basis of conventional anti-heart failure therapy, the control group received oral ferrous sulfate tablets, while the observation group received oral ferrous sulfate tablets combined with EPO subcutaneous injection. Blood indices, cardiac function and serology were determined and tested in all patients before treatment, and at 4 months after treatment.Results: After treatment, hemoglobin (Hb), hematocrit (HCT), red blood cell (RBC), blood platelet count (PLT) and serum iron were significantly higher than those before treatment in the two groups; the levels in the observation group were significantly higher than those in control group (p <0.05). Following treatment, left ventricular ejection fraction (LVEF), and 6-minute walking distance in the observation group were significantly higher than those in the control group, while end-diastolic dimension (LVEDD), end-systolic dimension (LVESD) and cardiac functional grading in the observation group were significantly lower than those in the control group (p < 0.05). After treatment, hs-CRP, Hcy and BNP were significantly lower than pre-treatment values in the two groups, while the values for the observation group were significantly lower than those of control group (p <0.05). Correlation analysis showed that LVEF and Hb were negatively correlated with hs-CRP, Hcy and BNP (p <0.05).Conclusion: Serum hs-CRP, Hcy and BNP are involved in the occurrence and progression of CHF with anemia. Exogenous EPO can effectively improve anemia and cardiac function in these patients.Keywords: Erythropoietin, Chronic heart failure, Anemia, C-reaction protein, B-type natriuretic peptid

MicroRNA-206: Effective Inhibition of Gastric Cancer Progression through the c-Met Pathway

MicroRNAs are endogenous short chain nucleotide RNAs that regulate gene function by direct binding of target mRNAs. In this study, we investigated the effects of microRNA-206 (miR-206) on the development of gastric cancer. miR-206 was first confirmed to be downregulated in gastric cancer specimens. Conversely, upregulation of c-Met was confirmed in tissue samples of human gastric cancer, with its level inversely correlated with miR-206 expression. Introduction of miR-206 inhibited cellular proliferation by inducing G1 cell cycle arrest, as well as migration and invasion. Moreover, important proliferation and/or migration related molecules such as c-Met, CDK4, p-Rb, p-Akt and p-ERK were confirmed to be downregulated by Western blot analysis. Targeting of c-Met also directly affected AGS cell proliferation, migration and invasion. In vivo, miR-206 expressing tumor cells also displayed growth delay in comparison to unaffected tumor cells. Our results demonstrated that miR-206 suppressed c-Met expression in gastric cancer and could function as a potent tumor suppressor in c-Met overexpressing tumors. Inhibition of miR-206 function could contribute to aberrant cell proliferation and migration, leading to gastric cancer development

1-Methyl-3,5-bis­(3-methyl­phen­yl)benzene

In the title compound, C21H20, the dihedral angles formed by the central benzene ring with the outer benzene rings are 21.43 (6) and 31.70 (4)°. The crystal packing is stabilized by a weak π–π stacking inter­action, with a centroid–centroid distance of 3.843 (3) Å

Sources of variation in nutrient intakes among men in Shanghai, China

Background and objective: Random errors, from any source, will attenuate epidemiological risk estimates. Before we launched the Shanghai Men’s Health Study (SMHS), a large population-based cohort study investigating the diet–cancer association among Chinese men, a dietary calibration study was conducted among 96 men aged 40–75 years (mean age 56.5 years), with biweekly 24-hour dietary recalls (24HDRs) implemented over a 1-year period. Data from this study were analysed to evaluate the nature and magnitude of variances for intake of 26 nutrients among SMHS participants, to compare variance ratios of 26 nutrients among Chinese men and women and individuals in other studies, and to estimate the number of 24HDRs required for future dietary calibration studies in similar populations. Design: Ninety-six healthy, free-living men in Shanghai were administered biweekly 24HDR interviews 24 times over a 1-year period. To assess between-individual and within-individual contributions to variance, a mixed effects model was fitted and ratios of within-individual to between-individual (s^ 2 w=s^ 2 b) dietary intake variances were computed. Setting: Shanghai, China. Results: In agreement with reports from studies conducted in the USA and many other countries, we found that within-individual variances were usually larger than between-individual variances in dietary intake for all nutrients. The sum of all other variation (e.g. weekday and weekend, seasonal, interviewer) accounted for less than 5% of total variation. Ratios of within- to between-individual variances (for logtransformed data) ranged from 1.25 for carbohydrate intake to near 8 for d-tocopherol intake. Conclusions: The results of this study suggest that among middle-aged and elderly Chinese men in Shanghai, within- and between-individual variation account for more than 95% of the total variation for 26 nutrients. Further dietary validation studies in the same population could be adequately carried out with only 12 days of dietary recalls, if 100 participants were enrolled

Spatial and temporal clonal evolution of intrahepatic cholangiocarcinoma

Background & Aims: Intrahepatic cholangiocarcinoma (ICC) is the second-most lethal primary liver cancer. Little is known about intratumoral heterogeneity (ITH) and its impact on ICC progression. We aim to investigate its ITH in hope of helping develop new therapeutic strategies. Methods: We obtained 69 spatially distinct regions from 6 operable ICCs. Patient-derived primary cancer cells (PDPCs) were established for each region, followed by whole-exome sequencing(WES) and multi-level validation. Results: We observed widespread ITH for both somatic mutations and clonal architecture, shaped by multiple mechanisms, like clonal “illusion”, parallel evolution and chromosome instability. A median of 60.3% mutations were heterogeneous mutations, among which 85% of the driver mutations located on the branches of tumor phylogenetic trees. Many truncal and clonal driver mutations occurred in tumor-suppressor genes, such as TP53, SMARCB1 and PBRM1 that involved in DNA repair and chromatin-remodeling. Genome doubling occurred in most cases (5/6) after the accumulation of truncal mutations and was shared by all intratumoral subregions. In all cases, ongoing chromosomal instability is evident throughout the evolutionary trajectory of ICC. The recurrence of ICC1239 provided evidence to support the polyclonal metastatic seeding in ICC. The change of mutation landscape and internal diversity among subclones during metastasis, such as the loss of chemoresistance mediator, may be used for new treatment strategy. Targeted therapy against truncal alterations, such as IDH1, JAK1, and KRAS mutations and EGFR amplification, could be developed in 5/6 patients. Conclusions: Integrated investigations of spatial ITH and clonal evolution may provide an important molecular foundation for enhanced understanding of tumorigenesis and progression in ICC. Lay summary: We applied multiregional whole exome sequencing to investigate the evolution trajectory of ICC. The results revealed that many fuels, such as parallel evolution and chromosome instability, may participate and promote the branch diversity of ICC. Interestingly, in one patient with primary and recurrent metastatic tumors, we found some clues of polyclonal metastatic seeding, indicating that symbiotic communities of multiple clones existed and were maintained during metastasis. More realistically, some truncal alterations, such as IDH1, JAK1, and KRAS mutations and EGFR amplification, can be promising treatment targets for ICC patients

The Bioavailability, Biodistribution, and Toxic Effects of Silica-Coated Upconversion Nanoparticles in vivo

Lanthanide-doped upconversion nanoparticles can convert long wavelength excitation radiation to short wavelength emission. They have great potential in biomedical applications, such as bioimaging, biodetection, drug delivery, and theranostics. However, there is little information available on their bioavailability and biological effects after oral administration. In this study, we systematically investigated the bioavailability, biodistribution, and toxicity of silica-coated upconversion nanoparticles administrated by gavage. Our results demonstrate that these nanoparticles can permeate intestinal barrier and enter blood circulation by microstructure observation of Peyer's patch in the intestine. Comparing the bioavailability and the biodistribution of silica-coated upconversion nanoparticles with oral and intravenous administration routes, we found that the bioavailability and biodistribution are particularly dependent on the administration routes. After consecutive gavage for 14 days, the body weight, pathology, Zn and Cu level, serum biochemical analysis, oxidative stress, and inflammatory cytokines were studied to further evaluate the potential toxicity of the silica-coated upconversion nanoparticles. The results suggest that these nanoparticles do not show overt toxicity in mice even at a high dose of 100 mg/kg body weight

Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer.

Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest, possibly because of dynamic changes in cellular signaling that drive resistance and limit drug efficacy. Using a quantitative chemoproteomics approach, we mapped kinome dynamics in response to inhibitors of this pathway and identified signaling changes that correlate with drug sensitivity. Maintenance of AURKA after drug treatment was associated with resistance in breast cancer models. Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo. This signaling map identifies survival factors whose presence limits the efficacy of targeted therapies and reveals new drug combinations that may unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer