Identification of a necroptosis-related prognostic gene signature associated with tumor immune microenvironment in cervical carcinoma and experimental verification.

Cervical carcinoma (CC) has been associated with high morbidity, poor prognosis, and high intratumor heterogeneity. Necroptosis is the significant cellular signal pathway in tumors which may overcome tumor cells' apoptosis resistance. To investigate the relationship between CC and necroptosis, we established a prognostic model based on necroptosis-related genes for predicting the overall survival (OS) of CC patients. The gene expression data and clinical information of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) patients were obtained from The Cancer Genome Atlas (TCGA). We identified 43 differentially expressed necroptosis-related genes (NRGs) in CESC by examining differential gene expression between CESC tumors and normal tissues, and 159 NRGs from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Gene ontology (GO) and KEGG enrichment analysis illustrated that the genes identified were mainly related to cell necrosis, extrinsic apoptosis, Influenza A, I - kappaB kinase/NF - kappaB, NOD - like receptor, and other signaling pathways. Subsequently, least absolute shrinkage and selection operator (LASSO) regression and univariate and multivariate Cox regression analyses were used to screen for NRGs that were correlated with patient prognosis. A prognostic signature that includes CAMK2A, CYBB, IL1A, IL1B, SLC25A5, and TICAM2 was established. Based on the prognostic model, patients were stratified into either the high-risk or low-risk subgroups with distinct survival. Receiver operating characteristic (ROC) curve analysis was used to identify the predictive accuracy of the model. In relation to different clinical variables, stratification analyses were performed to demonstrate the associations between the expression levels of the six identified NRGs and the clinical variables in CESC. Immunohistochemical (IHC) validation experiments explored abnormal expressions of these six NRGs in CESC. We also explored the relationship between risk score of this necroptosis signature and expression levels of some driver genes in TCGA CESC database and Gene Expression Omnibus (GEO) datasets. Significant relationships between the six prognostic NRGs and immune-cell infiltration, chemokines, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoints in CESC were discovered. In conclusion, we successfully constructed and validated a novel NRG signature for predicting the prognosis of CC patients and might also play a crucial role in the progression and immune microenvironment in CC.

LINC00511/hsa-miR-573 axis-mediated high expression of Gasdermin C associates with dismal prognosis and tumor immune infiltration of breast cancer.

Breast cancer (BC) is considered the second commonest human carcinoma and the most incident and mortal in the female population. Despite promising treatments for breast cancer, mortality rates of metastatic disease remain high. Gasdermin C (GSDMC) is an affiliate of the gasdermin (GSDM) family, which is involved in the process of pyroptosis. Pyroptosis is implicated in tumorigenesis, but the role of GSDMC in cancer cells is yet to be fully elucidated. In this study, we investigated the role and mechanism of GSDMC in breast cancer. We conducted a pan-cancer analysis of the expression and prognosis of GSDMC utilizing multidimensional data from The Cancer Genome Atlas (TCGA). We investigated GSDMC expression levels in 15 BC tissues and matched adjacent normal tissues by immunohistochemistry (IHC). Further verification was performed in the Gene Expression Omnibus (GEO) database. We discovered that elevated GSDMC expression was considerably linked to a worse prognosis in breast invasive carcinoma (BRCA). Next, we identified noncoding RNAs (ncRNAs) which contributing to higher expression of GSDMC by a series of expression, survival, and correlation analysis. We finally identified LINC00511/hsa-miR-573 axis to be the most promising ncRNA-associated pathways that account for GSDMC in BRCA. Furthermore, we demonstrated the significant correlations between GSDMC expression and immune infiltrates, immune checkpoints, and immune markers in BRCA. This study illustrated that ncRNAs-mediated upregulation of GSDMC linked to dismal prognosis and also exhibited a correlation with tumor immune cell infiltration in BRCA. It is anticipated to offer novel ideas for the link between pyroptosis and tumor immunotherapy.

Identification and validation of necroptosis-related prognostic gene signature and tumor immune microenvironment infiltration characterization in esophageal carcinoma.

BACKGROUND: Esophageal carcinoma (ESCA) is a common malignancy with a poor prognosis. Previous research has suggested that necroptosis is involved in anti-tumor immunity and promotes oncogenesis and cancer metastasis, which in turn affects tumor prognosis. However, the role of necroptosis in ESCA is unclear. This study aimed to investigate the relationships between necroptosis-related genes (NRGs) and ESCA. METHODS AND RESULTS: The clinical data and gene expression profiles of ESCA patients were extracted from The Cancer Genome Atlas (TCGA), and 159 NRGs were screened from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We then identified 52 differentially expressed NRGs associated with ESCA and used them for further analysis. Gene ontology (GO) and KEGG functional enrichment analyses showed that these NRGs were mostly associated with the regulation of necroptosis, Influenza A, apoptosis, NOD-like receptor, and NF-Kappa B signaling pathway. Next, univariate and multivariate Cox regression and LASSO analysis were used to identify the correlation between NRGs and the prognosis of ESCA. We constructed a prognostic model to predict the prognosis of ESCA based on SLC25A5, PPIA, and TNFRSF10B; the model classified patients into high- and low-risk subgroups based on the patient's risk score. Furthermore, the receiver operating characteristic (ROC) curve was plotted, and the model was affirmed to perform moderately well for prognostic predictions. In addition, Gene Expression Omnibus (GEO) datasets were selected to validate the applicability and prognostic value of our predictive model. Based on different clinical variables, we compared the risk scores between the subgroups of different clinical features. We also analyzed the predictive value of this model for drug sensitivity. Moreover, Immunohistochemical (IHC) validation experiments explored that these three NRGs were expressed significantly higher in ESCA tissues than in adjacent non-tumor tissues. In addition, a significant correlation was observed between the three NRGs and immune-cell infiltration and immune checkpoints in ESCA. CONCLUSIONS: In summary, we successfully constructed and validated a novel necroptosis-related signature containing three genes (SLC25A5, PPIA, and TNFRSF10B) for predicting prognosis in patients with ESCA; these three genes might also play a crucial role in the progression and immune microenvironment of ESCA.

LPAR2 correlated with different prognosis and immune cell infiltration in head and neck squamous cell carcinoma and kidney renal clear cell carcinoma.

BACKGROUND: Lysophosphatidic acid (LPA) and its receptors play a key role in regulating cancer progression. Upregulation of LPA receptor 2 (LPAR2) plays a role in carcinogenesis; however, the exact role of LPAR2 in tumors remains elusive. This study aims to explore the correlation between LPAR2 expression with tumor prognosis and immune infiltration in pan-cancers. MATERIALS AND METHODS: The expression of LPAR2 in pan-cancers was analyzed using the Online Cancer Microarray Database (Oncomine), Tumor Immune Estimation Resource (TIMER), and UALCAN databases. The effects of LPAR2 on the clinical prognosis in pan-cancer were examined using the Kaplan-Meier plotter (KM plotter) as well as Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and Human Protein Atlas (HPA) databases. Moreover, the R software program was applied for validation of expression and prognostic value of LPAR2 in tumor patients in the Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) database. The relationship between the expression level of LPAR2 and the clinical and molecular criteria of head and neck squamous cell carcinoma (HNSC) and kidney renal clear cell carcinoma (KIRC) was analyzed using UALCAN, whereas the relationship between LPAR2 expression and prognosis in patients with HNSC and KIRC with different clinical characteristics was examined using the KM plotter. Furthermore, the correlation between LPAR2 expression and tumor immune infiltration was examined using TIMER. The correlation between LPAR2 expression and gene markers of tumor immune infiltrates was analyzed using TIMER and GEPIA. In addition, the cBioPortal for Cancer Genomics was used to calculate the mutations, methylations, and altered neighbor genes of LPAR2. RESULTS: The expression of LPAR2 was significantly correlated with the outcome of multiple types of cancer, especially HNSC and KIRC. Furthermore, high expression of LPAR2 was significantly associated with various immune markers in the immune cell subsets of HNSC and KIRC. CONCLUSIONS: High expression of LPAR2 plays significantly different prognostic roles in HNSC and KIRC possibly owing to its association with different immune markers. LPAR2 is correlated with tumor immune cell infiltration and is a valuable prognostic biomarker for HNSC and KIRC. However, further experiments are required to validate these findings.

Shenling Baizhu Powder alleviates chronic inflammation to prevent type 2 diabetes of ZDF rats via intestinal flora / 中国中药杂志

This study explored the mechanism of Shenling Baizhu Powder(SLBZP) in the prevention and treatment of type 2 diabetes from the perspective of flora disorder and chronic inflammation. Fifty rats were randomly divided into normal control group, model control group, low-dose SLBZP group, medium-dose SLBZP group, and high-dose SLBZP group, with 10 rats in each group. The rats of 5 weeks old were administrated by gavage with ultrapure water and different doses of SLBZP decoction. The basic indicators such as body weight and blood glucose were monitored every week, and stool and intestinal contents were collected from the rats of 9 weeks old for 16 S rRNA sequencing and metabolomic analysis. An automatic biochemical analyzer was used to measure the serum biochemical indicators, ELISA to measure serum insulin, and chipsets to measure leptin and inflammatory cytokines. The results showed that SLBZP reduced the body weight as well as blood glucose, glycosylated hemoglobin, and lipid levels. In the rats of 9 weeks, the relative abundance of Anaerostipes, Turicibacter, Bilophila, Ochrobactrum, Acinetobacter, and Prevotella decreased significantly in the model control group, which can be increased in the high-dose SLBZP group; the relative abundance of Psychrobacter, Lactobacillus, Roseburia and Staphylococcus significantly increased in the model control group, which can be down-regulated in the high-dose SLBZP group. The differential metabolites of intestinal flora included 4-hydroxyphenylpyruvic acid, phenylpyruvic acid, octanoic acid, 3-indolepropionic acid, oxoglutaric acid, malonic acid, 3-methyl-2-oxovaleric acid, and methylmalonic acid. Moreover, SLBZP significantly lowered the levels of free insulin, insulin resistance and leptin resistance in rats. The variations in the serum levels of interleukin 1β(IL-1β) and monocyte chemoattractant protein-1(MCP-1) showed that SLBZP could alleviate chronic inflammation in rats. In conclusion, SLBZP can regulate intestinal flora and metabolites and relieve chronic inflammation to control obesity and prevent type 2 diabetes.

Pharmacoeconomic evaluation of Shexiang Tongxin Dropping Pills combined with conventional Western medicine treatment for coronary heart disease by Markov model / 中国中药杂志

This research was to evaluate the economics of Shexiang Tongxin Dropping Pills combined with conventional therapy for patients with coronary heart disease(CHD) in Chinese medical environment. From the perspective of medical insurance, a Markov model was established in this study based on the results of Meta-analysis comparing the effectiveness and safety of Shexiang Tongxin Dripping Pills combined with conventional treatment and conventional treatment alone. The experimental group was treated with She-xiang Tongxin Dropping Pills combined with conventional Western medicine treatment, while the control group was treated with conventional Western medicine treatment alone. The cost-utility analysis and sensitivity analysis were performed for the two regimens using Treeage pro. After 30 cycles of model simulation, according to the results of Markov model, the total cost and health output were CNY 237 795.73 and 16.36 QALYs(the quality adjusted life years, QALYs), respectively for Shexiang Tongxin Dropping Pills combined with conventional Western medicine treatment, CNY 247 396.55 and 16.36 QALYs respectively for the conventional Western medicine treatment alone. Compared with the conventional treatment alone, the Shexiang Tongxin Dropping Pills combined with conventional treatment had lower long-term cost and higher health output, with advantages of cost-utility and pharmacoeconomic advantages. The sensitivity analysis results showed that the conclusion was relatively stable. Based on the above results, it is considered that compared with the conventional Western medicine alone, Shexiang Tongxin Dropping Pill combined with conventional Western medicine is a treatment regimen with pharmacoeconomic advantages for the treatment of CHD.

Transcriptional Profile Alteration of Peripheral Blood in Chronic Hypoxia / 中国医学科学杂志(英文版)

Objective Many physiological and pathological conditions, including cyanotic congenital heart diseases (CCHD), are accompanied by chronic hypoxia, which might interfere with the transcription process. However, the transcriptome profile in peripheral blood under hypoxia is still unidentified. The present work aimed to explore the transcriptional profile alteration of peripheral blood in chronic hypoxia. Methods The present study used a chronic hypoxia rat model to simulate the hypoxic state of CCHD patients. Two groups of Sprague-Dawley rats (n=6 per group) were either exposed to hypoxia (10% O2) or normoxia (21% O2) for 3 weeks. Body weight was measured weekly. Peripheral blood was collected and total RNA was extracted for RNA-Seq at the end of the hypoxia treatment. After quality assessment, the library was sequenced by the Illumina Hiseq platform. The differentially expressed genes were screened (false discovery rate<0.05 and fold change>2). The functional annotation analysis and cluster analysis of differentially expressed genes were performed based on the adjusted P-value (padj<0.05). Results Compared with the control group, the body weight of the rats in the hypoxia group was significantly lowered (P<0.01). RNA-Seq results showed that the transcriptome patterns of the two groups had significant differences. In total, 872 genes were identified as differentially expressed. Among all, 803 genes were down-regulated, while only 69 genes were up-regulated in the hypoxia group. The functional enrichment analysis of the 872 genes showed that multiple biological processes involved, such as porphyrin-containing compound metabolic process, hemoglobin complex and oxygen transporter activity. Conclusions Our study demonstrated the transcriptional profile alteration in peripheral blood of chronic hypoxia rat model. This study provided basic data and directions to further understand the physiological and pathological changes in patients with CCHD.

Material Basis and Mechanism of Kaixinsan for Treatment of Alzheimer's Disease Based on Integrated Pharmacological Platform of Chinese Medicine / 中国实验方剂学杂志

Objective: To explore the interrelation of "composition-target-disease" of Kaixinsan on treatment of Alzheimer's disease. Method: Through the integrated pharmacological platform of Chinese medicine V1.0,the active ingredients and potential targets of four Chinese herbs in Kaixinsan were collected,disease targets of Alzheimer's disease were searched,and enriched by the gene ontology database and the Kyoto encyclopedia of genes and genomes at hubs. Result: Among the 250 compounds of Kaixinsan,2 877 targets were associated with Alzheimer's disease.The key targets,such as mitochondrial trifunctional enzyme subunit alpha(HADHA),hydroxyacyl coenzyme A dehydrogenase(HADH),sterol-4-alpha-carboxylate 3-dehydrogenase(NSDHL) and others,played their pharmacological effects mainly through regulating purine and nucleotide metabolism,Huntington's disease,Alzheimer's disease,neurodegenerative diseases,oxidative phosphorylation,and endocrine and metabolic diseases in molecular reactions,such as cytoplasm,mitochondria,adenosine triphosphate binding,and mitochondrial matrix. Conclusion: The platform can predict the key targets and related pathways of Kaixinsan for treatment of Alzheimer's disease,which lays the foundation for further revealing material basis and mechanism of this formula,and plays an important role in digging and developing this classic and famous formula.

Comparing the effects of depression, anxiety, and comorbidity on quality-of-life, adverse outcomes, and medical expenditure in Chinese patients with acute coronary syndrome / 中华医学杂志(英文版)

Background:@#Depression and anxiety have been correlated with elevated risks for quality-of-life (QOL), adverse outcomes, and medical expenditure in patients with acute coronary syndrome (ACS). However, the relevant data are lacking for Chinese ACS populations, especially regarding different effects of major depression, anxiety, and comorbidity. The objective of this study was to evaluate the dynamic changes of depression and/or anxiety over 12 months and examine the effects of depression, anxiety, and comorbidity on QOL, adverse outcomes, and medical expenditure in Chinese patients with ACS.@*Methods:@#For this prospective longitudinal study, a total of 647 patients with ACS were recruited from North China between January 2013 and June 2015. Among them, 531 patients (82.1%) completed 12-month follow-ups. Logistic regression model was utilized for analyzing the association of baseline major depression, anxiety, and comorbidity with 12-month all-cause mortality, cardiovascular events, QOL, and health expenditure.@*Results:@#During a follow-up period of 12 months, 7.3% experienced non-fatal myocardial infarction (MI) and 35.8% cardiac rehospitalization. Baseline comorbidity, rather than major depression/anxiety, strongly predicted poor 12-month QOL as measured by short-form health survey-12 (odds ratio [OR]: 1.77, 95% confidence interval [CI]: 1.22–2.52, P = 0.003). Regarding 12-month non-fatal MI and cardiac re-hospitalization, baseline anxiety (OR: 2.83, 95% CI: 1.33–5.89, P < 0.01; OR: 4.47, 95% CI: 1.50–13.00, P < 0.01), major depression (OR: 2.58, 95% CI: 1.02–6.15, P < 0.05; OR: 5.22, 95% CI: 1.42–17.57, P < 0.03), and comorbidity (OR: 6.33, 95% CI: 2.96–13.79, P < 0.0001, OR: 14.08, 95% CI: 4.99–41.66, P < 0.0001) were all independent predictors, and comorbidity had the highest predictive value. Number of re-hospitalization stay, admission frequency within 12 months and medical expenditure within 2 months were the highest in patients with ACS with comorbidity.@*Conclusions:@#Major depression and anxiety may predict 12-month non-fatal MI and cardiac re-hospitalization. However, comorbidity has the highest predictive value with greater medical expenditure and worse QOL in Chinese patients with ACS. And depression with comorbid anxiety may be a new target of mood status in patients with ACS.

Comparing the effects of depression, anxiety, and comorbidity on quality-of-life, adverse outcomes, and medical expenditure in Chinese patients with acute coronary syndrome / 中华医学杂志(英文版)

BACKGROUND@#Depression and anxiety have been correlated with elevated risks for quality-of-life (QOL), adverse outcomes, and medical expenditure in patients with acute coronary syndrome (ACS). However, the relevant data are lacking for Chinese ACS populations, especially regarding different effects of major depression, anxiety, and comorbidity. The objective of this study was to evaluate the dynamic changes of depression and/or anxiety over 12 months and examine the effects of depression, anxiety, and comorbidity on QOL, adverse outcomes, and medical expenditure in Chinese patients with ACS.@*METHODS@#For this prospective longitudinal study, a total of 647 patients with ACS were recruited from North China between January 2013 and June 2015. Among them, 531 patients (82.1%) completed 12-month follow-ups. Logistic regression model was utilized for analyzing the association of baseline major depression, anxiety, and comorbidity with 12-month all-cause mortality, cardiovascular events, QOL, and health expenditure.@*RESULTS@#During a follow-up period of 12 months, 7.3% experienced non-fatal myocardial infarction (MI) and 35.8% cardiac re-hospitalization. Baseline comorbidity, rather than major depression/anxiety, strongly predicted poor 12-month QOL as measured by short-form health survey-12 (odds ratio [OR]: 1.77, 95% confidence interval [CI]: 1.22-2.52, P = 0.003). Regarding 12-month non-fatal MI and cardiac re-hospitalization, baseline anxiety (OR: 2.83, 95% CI: 1.33-5.89, P < 0.01; OR: 4.47, 95% CI: 1.50-13.00, P < 0.01), major depression (OR: 2.58, 95% CI: 1.02-6.15, P < 0.05; OR: 5.22, 95% CI: 1.42-17.57, P < 0.03), and comorbidity (OR: 6.33, 95% CI: 2.96-13.79, P < 0.0001, OR: 14.08, 95% CI: 4.99-41.66, P < 0.0001) were all independent predictors, and comorbidity had the highest predictive value. Number of re-hospitalization stay, admission frequency within 12 months and medical expenditure within 2 months were the highest in patients with ACS with comorbidity.@*CONCLUSIONS@#Major depression and anxiety may predict 12-month non-fatal MI and cardiac re-hospitalization. However, comorbidity has the highest predictive value with greater medical expenditure and worse QOL in Chinese patients with ACS. And depression with comorbid anxiety may be a new target of mood status in patients with ACS.

PPARγ non-agonist ligand:the structure optimization based on PPARγ partial agonist / 药学学报

Recent studies indicate that insulin-sensitizing activity of TZDs occurs through the inhibition of PPARγ Ser273 phosphorylation mediated by cyclin-dependent kinase 5(Cdk5), which is resulted from the binding activity for PPARγ. While, the side effects of TZDs may be related to the agonistic potency for PPARγ. In this article, 15 target compounds were designed and synthesized based on the structure of PPAR γ partial agonist INT131, with the aim of maintaining the insulin-sensitizing activity and reducing the side effects of INT131. The structures of these compounds were confirmed by 1H NMR and ESI-MS, and their binding activities and agonistic potencies for PPARγ were measured. The binding activity of compound 15 is 88.47% of rosiglitazone, which is similar to INT131 (98.55%), but the agonistic potency of compound 15 is 1.41% of rosiglitazone, obviously lower than INT131 (15.18%).

The anti-tumor activity and molecular mechanisms of an Aurora kinase inhibitor ZLJ213 in suppressing colon cancer growth / 药学学报

The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT1 16 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg · kg(-1) inhibited tumor growth by 73.24%. The IC50 of ZLJ213 on the expression of p-Aurora A was 0.258 µmol · L(-1) analyzed by ELISA. Under the concentration of 0.08 µmol · L(-1), ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer.

Synthesis and in vitro cytotoxic activities of sorafenib derivatives / 药学学报

A series of novel sorafenib analogues were designed and synthesized. The cytotoxic activities of these compounds were tested in four tumor cell lines. Some of the compounds showed potent antiproliferative activity against the tested cell lines with IC50 = 4-20 micromol x L(-1). Some compounds demonstrated competitive antiproliferative activities to sorafenib against tested cancer cell lines. Among them, compound 7c demonstrated significant inhibitory activities on ACHN, HCT116 and MDA-MB-231 cell lines with IC50 values of 9.01, 4.97, 6.61 micromol x L(-1), respectively.

The biological function of miR-214 in colon cancer HCT116 cells / 肿瘤

Objective: To investigate the expression of miR-214 (microRNA-214) in different colon cancer cell lines and its effect on the proliferation and apoptosis of HCT116 cells. Methods: The expressions of miR-214 and PIM1 mRNA in different colon cancer cell lines were detected by real-time fluorogenic quantitative-PCR, and the relationship between miR-214 and PIM1 mRNA expression was evaluated. The miR-214 mimics was transfected into HCT116 cells by LipofectAMINE 2000, then the expressions of miR-214 and PIM1 mRNA levels were detected by real-time fluorogenic quantitative-PCR. The change of proliferation ablility of HCT116 cells was detected by MTT method and colony-formation assay. The flow cytometry was used to examine the changes of apoptosis and cell cycle distribution. Results: The expression of miR-214 was down-regulated in HCT116 cells. The expression of miR-214 was negatively correlated with the expression of PIM1 mRNA in colon cancer cells (r = -0.943, P = 0.016). After transfection with miR-214 mimics, the expression level of miR-214 was up-regulated as compared with no transfection. The high expression level of miR-214 increased in miR-214 mimics group compared with that in the negative control group (P < 0.01). The high expression level of miR-214 could significantly inhibit the expression of PIM1 mRNA. After transfection with miR-214 mimics, the number of colonies was decreased (P = 0.026 9), the cell growth was inhibited (P < 0.000 1), the apoptosis rate was increased (P = 0.010 4), and the proportion of G1-stage cells was decreased as well as the proportion of S-stage cells was increased. Conclusion: MiR-214 can inhibit the proliferation and promote the apoptosis of colon cancer HCT116 cells. MiR-214 may act as a tumor suppressor in colorectal cancer by inhibiting PIM1. Copyright © 2013 by TUMOR.

Design, synthesis and antitumor activity of sorafenib analogues containing 2-picolinylhydrazide moiety / 药学学报

A novel series of sorafenib analogs containing 2-picolinyl hydrazide moiety were designed and synthesized. In vitro, most of synthesized compounds have antiproliferation activity on MDA-MB-231, ACHN, HepG2, Mia-PaCa-2 and SW1990 cell lines tested by MTT assay. It is worth noting that the antitumor activities of compounds 2c, 2d and 2f are more potent than that of sorafenib on pancreatic cancer cells Mia-PaCa-2 and SW1990, and the activities of compounds 3f and 3g are 2-3 times than that of sorafenib on human hepatocellular carcinoma HepG2 cell line.

Reference values of brachial-ankle pulse wave velocity for Northern Chinese / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Brachial-ankle pulse wave velocity (baPWV) is a reliable method for measuring arterial elasticity, but the absence of reference value for baPWV has limited its wide use. We conducted an epidemical study in north China to investigate the reference value of baPWV for Chinese people and its influential factors.</p><p><b>METHODS</b>A total of 974 identified healthy subjects were recruited in this study. The values of baPWV were evaluated noninvasively with an automatic device.</p><p><b>RESULTS</b>For healthy population, the mean value of baPWV was higher for male (P < 0.001). Multiple regression analysis demonstrated that both age and systolic blood pressure were positively associated with baPWV for male and female (P < 0.001). BaPWV value was higher in male than in female in younger group (< 50 years) but not in older group (P <or= 0.001). The upper limits of baPWV were 1394/1264 cm/s, 1435/1361 cm/s, 1552/1433 cm/s, 1597/1609 cm/s and 1798/1915 cm/s for healthy male/female at 10 years interval (age range 20 - 70 years).</p><p><b>CONCLUSIONS</b>Aging is the most important reason of arterial stiffness, but the effect of age on baPWV augmentation is greater for healthy female than their male counterpart. The reference values of baPWV by sex and age are very useful for clinical and preventive medicine.</p>

Effects of dietary supplementation with clostridium butyricum on the growth performance and humoral immune response in Miichthys miiuy / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The effects of dietary supplementation with Clostridium butyricum on growth performance and humoral immune response in Miichthys miiuy were evaluated. One hundred and fifty Miichthys miiuy weighing approximately 200-260 g were divided into five groups and reared in 15 tanks with closed circuiting culture system. The animals were fed 5 diets: basal diet only (control) or supplemented of the basal diet with C. butyricum at doses of 10(3) (CB1), 10(5) (CB2), 10(7) (CB3) or 10(9) (CB4) CFU/g. Compared with the control, the serum phenoloxidase activity was significantly increased by the supplementation (P<0.05), acid phosphatases activity was increased significantly (P<0.05) at the doses of 10(9) CFU/g. Serum lysozyme activity peaked at dose of 10(7) CFU/g and in the skin mucus at dose of 10(9) CFU/g. Immunoglobulin M level in the serum and skin mucus was increased except at dose of 10(3) CFU/g (P<0.05). The growth at the dose of 10(9) CFU/g was higher than that of the control (P<0.05). It is concluded that supplementation of C. butyricum can mediate the humoral immune responses and improve the growth performance in Miichthys miiuy.