Distribution Mechanism of Network Modules in Combined Treatment of Liver Cancer with Jiuwei Zhengxiao Granules / 中国实验方剂学杂志

ObjectiveTo explore the distribution mechanism of network modules in the combined treatment of liver cancer with Jiuwei Zhengxiao granules （JWZX） based on the analysis framework of module pharmacology. MethodThe cell experiment and the animal experiment were carried out to investigate the in vitro anti-liver cancer efficacy of JWZX of different concentrations and the effect on the survival time of H22 ascites tumor mice. By virtue of the analysis strategy of modular pharmacology，the distribution characteristics of nine Chinese drugs in the liver cancer disease network modules were investigated based on the constructed liver cancer disease network and module division by MCODE. In this study，the average degree （AD） of the nodes in the modules was used as an index to screen the main modules of the disease，and the intervention of the sovereign drugs，minister drugs，and assistant drugs on the main modules was explored. Finally，the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed on the drug-acted modules by Metascape. ResultAs revealed by the cell experiment，JWZX could significantly inhibit the proliferation of H22 cells. The animal experiment demonstrated that the medium- and high-dose JWZX could significantly prolong the survival time of mice with H22 ascites tumor （P<0.05，P<0.01）. The distribution of targets of JWZX in the liver cancer disease network modules showed that JWZX interfered with tumor necrosis factor （TNF），epidermal growth factor receptor （EGFR），vascular endothelial growth factor A （VEGFA），transcription factor （JUN），tumor protein p53 （TP53），and other 26 targets and 8 modules. The sovereign drug Ginkgo Semen mainly intervened in modules 3 and 8，and the minister drugs such as Centipeda Herba jointly intervened in modules 1，3，5，8，10，and 12. Centipeda Herba and Phyllanthi Fructus intervened in module 7 and module 19 individually. Artemisiae Annuae Herba and other assistant drugs jointly intervened in modules 3，5，10，and 12. KEGG pathway enrichment analysis found that 135 pathways were enriched in 8 modules，and the pathway functions involved 12 categories including cancer，signal transduction，immune system，endocrine system，and amino acid metabolism. The functions of the four major modules involved cancer，signal transduction，and immune system. According to the results of literature verification，the key links of JWZX on the liver cancer disease network and the core mechanism were presumedly related to the inhibition of phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） and hypoxia-inducible factor-1 （HIF-1） signaling pathways，reduction of the immunosuppressive effect in the tumor microenvironment，and improvement of the anti-tumor immune response. ConclusionJWZX possesses pharmacological activity against liver cancer，and the therapeutic efficacy was achieved through the multiple targets，multiple modules，and multiple functions of drugs alone or in combination to intervene in the disease. The present study reduced the complexity of drug-disease target network analysis with module analysis strategy and explored the network module distribution mechanism of JWZX in the treatment of liver cancer，which provides a new idea for interpreting the complex mechanism of prescription compatibility.

Inhibitory effect of Xiaochuan pill on obstinate cough and its role in regulation of TLR4MyD88NFκBp65 signaling pathway / 中南大学学报(医学版)

OBJECTIVES@#Cough variant asthma (CVA) is the main cause of obstinate cough. This study aimed to observe the therapeutic effect of Xiaochuan pill on CVA in a rat model, and to explore the mechanisms.@*METHODS@#The rats were sensitized and challenged with 4% ovaibumin (OA) and 2% Al(OH) to establish the CVA models. They were treated with Xiaochuan pill (at the dose of 0.9, 1.8, 3.6 g/kg) or montelukast sodium once a day for 14 days. After 7 and 14 days of intervention, 5 and 10 rats were randomly selected from each group to collect bronchoalveolar lavage fluid (BALF), trachea, and lungs. The number of white blood cells (WBC) and eosinophils (EOS), and the levels of IL-1β, TNF- α, and IFN-γ in BALF were detected. Histopathological examination of lung tissue was performed to observe the histomorphological changes. The expressions of TLR4, MyD88, NF-κBp65, and p-p65 in lung tissue were detected by Western blotting.@*RESULTS@#The numbers of WBC and EOS in BALF of CVA rats were significantly decreased by Xiaochuan pill (<0.05 or <0.01). The hyperplasia of tracheal, bronchial mucosa and the infiltration of inflammatory cells in lung were alleviated obviously. After 14 d of intervention, high dose of Xiaochuan pill significantly increased the level of IFN- γ (<0.01), reduced the levels of IL-1β (<0.05) and TNF-α (<0.05), and decreased the expressions of TLR4, MyD88, p65, and p-p65 (<0.05 or <0.01).@*CONCLUSIONS@#Xiaochuan pill exerts the significant therapeutic effect on obstinate cough in rats. The mechanism of action may be related to the regulation of TLR4-MyD88-NF-κBp65 signaling pathway as well as the inflammation and immune response.

The rapid diagnosis value of T-SPOT .TB for smear negative pulmonary tuberculosis / 国际检验医学杂志

Objective To evaluate the diagnostic value of Tuberculosis Infection in T Cell Test(T‐SPOT .TB) for smear negative pulmonary tuberculosis .Methods Separately used T‐SPOT .TB ,TB‐DNA ,TB‐DOT the three diagnostic methods for tuberculosis , separately detected with each method ,112 smear negative pulmonary tuberculosis ,and 60 non tuberculosis regarded as control group .Results The sensitivity of T‐SPOT .TB ,TB‐DNA ,TB‐DOT in proper sequence were 88 .3% ,25 .9% ,58 .9% .Contrasted to TB‐DNA and TB‐DOT ,the differences were statistically significant(X2 =86 .6 ,P<0 .01 ;X2 =23 .3 ,P<0 .01);the specificity of T‐SPOT .TB was 96 .7% ,significantly higher than TB‐DOT (78 .3% ) ,the differences were statistically significant(X2 = 9 .22 ,P<0 .05) .Conclusion T‐SPOT .TB has obvious advantages in sensitivity and specificity for smear negative pulmonary tuberculosis .It can be one auxiliary tool for smear negative pulmonary tuberculosis early diagnosis ,provided with the value of fast and accurate .