Effect of safflower yellow on learning and memory ability of APP/PS1 at different months based on TLR4/NF-KB signaling pathway / 中国药理学通报

Aim To investigate the effect of safflower yellow (SY) on learning and memory ability of APP/ PS1 mice at different disease stages, and to explore the mechanism of SY anti- Alzheimer's disease by using 3-,6- and 9-month-old APP/PS 1 transgenic mice as experimental animal models. Methods Behavioral experiments were conducted to observe the effects of SY on learning and memory of APP/PS1 mice of different months. ELISA was used to detect the effect of SY on the expression of inflammatory factors in cortex of mice of different months. Western blot was used to detect the microglia activation marker protein, and its mechanism of action was further analyzed. Results SY could enhance the learning and memory ability of mice aged 3, 6 and 9 months, reduce the content of IL-6 and increase the content of TGF-β1 in brain tissue, up-regulate the expression levels of arginase-1 (arg-1) and triggering receptor expressed on myeloid cells 2 (tREM2) in brain tissue of mice of different months, and down-regulate the expression levels of inducible nitric oxide synthase (iNOS), Toll-like receptors 4 (tlr4) and nuclear factor-kappa B (nf-KB). Conclusions Compared with 3- and 9-month-old mice, SY is the most effective in improving learning memory in 6-month-old APP/PS1 mice. SY inhibits TLR4/NF-KB pathway activation by inducing TREM2 expression in brain tissue of APP/PS 1 transgenic mice, promotes microglia phenotype shift to anti-inflammatory phenotype, reduces chronic neuroinflammatory response, and improves learning memory in APP/PS1 mice at all months of age.

Progressin Tumor-Associated Macrophages in the Treatment of Pancreatic Cancer / 中国医学科学院学报

Pancreatic cancer is one of the digestive system tumors with a high degree of malignancy,and most of the patients are diagnosed in advanced stages.Because of limited available therapies,the mortality of this disease remains high.Tumor-associated macrophages(TAM),the main immune cells in the tumor microenvironment,are involved in the regulation of the occurrence and development of pancreatic cancer.Specifically,TAM are involved in the proliferation,invasion,immune escape,and chemoresistance of pancreatic cancer cells,demonstrating potential in the targeted therapy of pancreatic cancer.In this paper,we summarize the TAM-based therapies including consuming TAM,reprogramming TAM,dynamic imaging of TAM with nanoprobes,and regulating the phagocytic ability of TAM for pancreatic cancer,aiming to provide a theoretical basis for developing new therapies for pancreatic cancer.

Research strategies and applications of functional metabolomics in anti-depressive mechanisms of traditional Chinese medicine / 药学学报

Depression is a common emotional disorder that seriously affects people's life and health all over the world. The pathogenesis of depression is complex, and traditional Chinese medicine (TCM) for antidepressants has a good therapeutic effect because of its multi-component, multi-pathway, and multi-target action mode. At present, the anti-depressive mechanism of TCM has not been fully clarified, but it is clear that depression is closely related to metabolic health. Therefore, in order to further explore the anti-depressive mechanism of TCM, this paper proposes research strategies on the anti-depressive mechanism of TCM based on functional metabolomics from the perspective of metabolism, the potential biomarkers of depression are analyzed with the help of multi-omics combined analysis technology, and the functional molecules of TCM for antidepressant are studied. Molecular biology techniques are used to accurately capture the molecular interactions between biomarkers of depression and functional compounds, which identify effective drug targets and further elucidate the biochemical functions and related mechanisms involved in depression metabolic disorders. This paper systematically reviews the research strategies and applications of functional metabolomics in the anti-depressive mechanisms of TCM, expounds on the core value of functional metabolomics, and summarizes the current research status and hot issues of TCM for antidepressants in recent years, providing new methods and new ideas for the study of mechanisms of TCM with the help of functional metabolomics.

A scoring system to predict molecular responses in patients with chronic myeloid leukemia in the chronic phase receiving initial imatinib therapy / 中华血液学杂志

Objective: To develop a scoring system to predict molecular responses in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving initial imatinib therapy. Methods: Data from consecutive adults with newly diagnosed CML-CP treated by initial imatinib was interrogated and subjects were distributed randomly into training and validation cohort, in a ratio of 2∶1. Fine-gray models were applied in the training cohort to identify co-variates of predictive value for major molecular response (MMR) and MR4. A predictive system was built using significant co-variates. The predictive system was then tested in the validation cohort and the area under the receiver-operator characteristic curve (AUROC) was used to estimate accuracy of the predictive system. Results: 1 364 CML-CP subjects receiving initial imatinib were included in this study. Subjects were distributed randomly into training cohort (n=909) and validation cohort (n=455) . In the training cohort, the male gender, European Treatment and Outcome Study for CML (EUTOS) Long-Term Survival (ELTS) intermediate-risk, ELTS high-risk, high WBC (≥130×10(9)/L or 120×10(9)/L, MMR or MR4) and low HGB (<110 g/L) at diagnosis were significantly related with poor molecular responses and were given points based on their regression coefficients. For MMR, male gender, ELTS intermediate-risk and low HGB (<110 g/L) were given 1 point; ELTS high-risk and high WBC (≥130×10(9)/L) , 2 points. For MR4, male gender was given 1 point; ELTS intermediate-risk and low HGB (<110 g/L) were given 2 points; high WBC (≥120×10(9)/L) , 3 points; ELTS high-risk, 4 points. We divided all subjects into 3 risk subgroups according to the predictive system above. Cumulative incidence of achieving MMR and MR4 in 3 risk subgroups was significantly different in both training and validation cohort (all P values <0.001) . In the training and validation cohorts, the time-dependent AUROC ranges of MMR and MR4 predictive systems were 0.70-0.84 and 0.64-0.81, respectively. Conclusions: A scoring system combining gender, WBC, HGB level and ELTS risk was built to predict MMR and MR4 in CML-CP patients receiving initial imatinib therapy. This system had good discrimination and accuracy, which could help phsicians optimize the selsction of initial TKI-therapy.

Repeatability and Reproducibility of Quantitative Assessment of the Retinal Microvasculature Using Optical Coherence Tomography Angiography Based on Optical Microangiography / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The aim of this study was to determine the repeatability and reproducibility of optical coherence tomography angiography (OCTA) based on optical microangiography (OMAG) measurements of macular vessels in normal eyes.</p><p><b>METHODS</b>In this prospective cohort study, 40 eyes of 40 healthy volunteers underwent repeated OCTA (Cirrus HD-OCT 5000 angiography system, Carl Zeiss Meditec, Inc.) scans on two separate visit days. On each visit day, the eyes were scanned three times. The following parameters were used to quantitatively describe the OCTA images of the superficial vascular network: vessel area density (VAD), vessel skeleton density (VSD), vessel diameter index (VDI), vessel perimeter index (VPI), vessel complexity index (VCI), flux, and foveal avascular zone (FAZ). Coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated for evaluating intravisit and intervisit repeatability, as well as interobserver reproducibility.</p><p><b>RESULTS</b>The measurements showed high repeatability [CVs ⪕ 4.2% (intravisit) and ⪕ 4.6% (intervisit)] and interobserver reproducibility (ICCs ⪖ 0.923) for all parameters.</p><p><b>CONCLUSION</b>This study demonstrated good repeatability and reproducibility of OCTA based on OMAG for the measurement of superficial vessel parameters in normal eyes.</p>

Expressions and significance of COX-2 and P-gp in human hepatocellular carcinoma tissues / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effect of the COX-2 gene on the oncogenesis and development of the hepatocellular carcinoma and the influence of COX-2 gene on the expression of P-gp protein.</p><p><b>METHOD</b>Fifty-two pieces of the hepatocellular carcinoma samples and 20 cases of normal liver samples were collected from the patients operated from October 2003 to June 2005. RT-PCR and immunohistochemistry staining were employed to detect the COX-2 mRNA as well as P-gp protein in the normal liver tissues and the carcinoma tissues. Meanwhile, the expression of the mdr 1 mRNA in the carcinoma tissues was also determined and the correlation between the expressions of the COX-2 and P-gp was investigated.</p><p><b>RESULTS</b>No expression of the COX-2 in the normal liver tissue was detected. The positive expression of COX-2 in the low and middle differentiated carcinoma was elevated significantly as compared with that in the high differentiated carcinoma tissue (x2 = 6.80, P less than 0.01). The positive expression of the COX-2 in the HBSAg (+) carcinoma tissue was significantly higher as compared with that in the HBSAg (-) carcinoma (x2 = 4.70, P less than 0.05), and the carcinoma in combination with cirrhosis also showed significantly higher in expression of COX-2 than the carcinoma without cirrhosis (x2 = 7.51, P less than 0.01). The mdr1 mRNA was found both expressed in the normal and carcinoma tissues. The expression of COX-2 mRNA was found in the carcinoma, but not found in the normal tissues. The COX-2 mRNA and mdr1 mRNA was found both expressed in the normal and carcinoma tissues. The correlation coefficient between COX-2 and mdr1 mRNA was 0.563 ( P less than 0.01).</p><p><b>CONCLUSION</b>The results indicated that Cox-2 gene might involved in the multidrug resistance of the hepatocellular carcinoma mediated by P-gp.</p>