Effects of six kinds of Chinese herb extracts, including Folium Crataegi extract, Herba Epimedii extract, Folium Acanthopanacis Senticosi extract, Trifolium pratense L. extract, Folium Ginkgo extract and Radix Puerariae extract, on the activities of CYP450 isozymes (CYP1A2, CYP2C, CYP2E1, CYP2D, CYP3A) in rat hepatic microsomals were studied by using a UPLC-MS/MS (MRM) and cocktail probe substrates method. The results showed that effects of six kinds of Chinese herb extracts on each CYP450 isozyme activity were inhibitory. The IC50 of Folium Crataegi extract for the inhibition of rat microsomal CYP2D activity was only for 4.04 microg x mL(-1), which showed the highest inhibition; Trifolium pratense L. extract had strong inhibitory action to CYP2D, the IC50 value was 5.73 microg x mL(-1); Folium Crataegi extract also had strong inhibitory action on CYP2E1, the IC50 value was 10.91 microg x mL(-1). Furthermore, the IC50 of Folium Ginkgo extract for the inhibition of rat microsomal CYP3A, 2D, 2E1 activities were 45.12, 35.45 and 22.41 microg x mL(-1), respectively, and the IC50 of Folium Acanthopanacis Senticosi extract on the inhibition of rat microsomal CYP2E1 activity was 32.89 microg x mL(-1). In addition, mechanism of inhibition experimental results showed that the inhibiting abilities of Folium Crataegi extract and Radix Puerariae extract on each CYP450 isozyme increased with the increasing of the preincubation time, therefore, the inhibitory effects were a mechanism-based inhibition.

BACKGROUND:Dexamethasone can improve the cellapoptosis and decrease the number of osteoblasts and bone cells through increasing the time of cellcycle. Protein kinase C is a kind of intraecellular singnal transduction pathways, and there are related reports on the relationship between protein kinase C and cellapoptosis. OBJECTIVE:To investigate the mechanism of dexamethasone-induced osteoblast apoptosis via protein kinase C intracellular signal transduction pathway. METHODS:Fetal rat bone marrow mesenchymal stem cells were col ected for osteogenic induction, and the cells were divided into dexamethasone group, phorbol group and star cytochalasin group. The cells in the dexamethasone group were added with 1×10-6 mol/L dexamethasone, the cells in the phorbol group were added with 1×10-6 mol/L dexamethasone and 1×10-7 mol/L phorbol, while the cells in the star cytochalasin group were added with 1×10-6 mol/L dexamethasone and 1×10-7 RESULTS AND CONCLUSION:Dexamethasone could induce apoptosis significantly, and after added with mol/L star cytochalasin. The proliferation and inhibition of the cells in different intervention groups were observed, and the content of protein kinase C in the cellmembrane and cytoplasm was measured. phorbol, the apoptosis was increased significantly;while after added with star cytochalasin, the apoptosis was decreased significantly. After added with dexamethasone, the content of protein kinase C in the cytoplasm was significantly decreased, while increased in the cellmembrane. At different time points after added with dexamethasone, the change of the content of protein kinase C in the cytoplasm and cellmembrane was most significant at 30 minutes. The results indicated that mechanism of dexamethasone-induced osteoblast apoptosis was correlated with protein kinase C, and dexamethasone was the agonist of protein kinase C. After the cells were stimulated, the protein kinase C in the cytoplasm wil moved to the cellmembrane, and then the content of protein kinase C in the cytoplasm was decreased, while increased in the cellmembrane.

Objective Neutrophil/lymphocyte ratio (NLR) is a simple and reliable inflammation biomarker but few studies have assessed the relationship between NLR and hypertension in Chinese population. In order to evaluate how NLR is related to the incidence of hypertension, we designed a large scale prospective cohort study in an adult population. Method Participants were recruited from Tianjin Medical University's General Hospital?Health Management Centre. Hypertension?free subjects (men, 13 638;women,15 212) were followed up for a median of 2.7 years. Adjusted Cox proportional hazards regression models were used to assess relationships between the quintiles of NLR and the incidence of hypertension. Result During the follow-up period, 1 348 subjects in men and 476 subjects in women developed hypertension. The hazard ratios of hypertension incidence were evaluated in increasing NLR quintiles both in men and women. In the final multivariate models, the hazard ratios (95% confidence interval) for hypertension across NLR quintiles were 1.00 (Reference), 1.05 (0.87, 1.26), 1.02 (0.85, 1.22), 1.07 (0.90, 1.29) and 1.22 (1.03, 1.45) (P for trend=0.01), in men;1.00 (Reference), 1.11 (0.82, 1.49), 0.79 (0.58, 1.08), 1.13 (0.85, 1.52) and 1.25 (0.94, 1.66) (P for trend=0.07), in women, respectively. Conclusion This study showed that the elevated NLR levels were significantly related to an increased risk of developing hypertension in men, but not in women.

Alzheimer disease (AD) is a chronic neurodegenerative disease that is characterized by its gradual progression. At present, the cause and mechanism of AD are yet unclear, and there is no effective therapy for treating it. With development of global aging, the prevalence rate of AD is increasing. The life quality of elderly people is affected severely by AD that is ultimately life-threatening. Recently, study on treating AD with traditional Chinese medicine (TCM) has deepened.

ObjectiveTo investigate the mechanism of action of Sini powder in the treatment of liver cancer based on network pharmacology and molecular docking. MethodsTraditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to obtain the compound and target of Sini powder, and the corresponding gene Symbol was obtained through Uniprot. The disease genes of liver cancer were obtained from Human Genome Database, and the genes with intersection with the target genes of Sini powder were screened out. Cytoscape3.7.1 software was used to draw the map of “traditional Chinese medicine (TCM)-compound-target” network. STRING was used to construct a protein-protein interaction (PPI) network, R studio software was used to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on therapeutic targets, and then the results were visualized. The active component with the highest number of targets was selected as the ligand, and the target with the highest degree in the PPI network was selected as the receptor, so as to predict the structure of receptor-ligand complex and the amino acid residues that bind to each other. ResultsIn this study, 91 core targets and 141 relevant active components of Sini powder were screened out, among which quercetin and kaempferol were the main active components in the treatment of liver cancer. TP53 and HSP90AA1 were the main therapeutic targets. The GO enrichment analysis obtained 1007 items which met the screening criteria, which were mainly involved in the biological processes of antioxidation reaction, activity regulation of protein serine and threonine kinase, and cellular stress response. The KEGG enrichment analysis obtained 102 pathways, which mainly regulated the hepatitis B pathway and the PI3K-Akt signaling pathway in the prevention and treatment of liver cancer. The results of molecular docking showed a synergistic antitumor effect between the crystal structure domains VAL147, CYS220, GLU221, and PRO222 of quercetin-TP53. ConclusionThis study reveals the mechanism of action of Sini powder in the treatment of liver cancer by acting on multiple targets and signaling pathways, which provides a theoretical basis for biological experiments.

Pannexin-1 (Panx1) forms nonselective large channel in cell plasma membrane and has been shown to be associated with NLRP3 inflammasome activation, ATP release and phagocytes recruitment. In the current study, by manipulation of Panx1 expression in human myeloid cells and application of Panx1 deficient mice, we failed to find a correlation between Panx1 and NLRP3 inflammasome activation, although an interaction between these two proteins was evident. However, in thioglycollate induced peritonitis, Panx1 deficient mice showed much more phagocytes infiltration. Further analyses showed that mice deficient for Panx1 exhibited enlarged F4/80(low)Gr1(-)Ly6C(-)cell population in the peritonea. Our study thus reveals an important role for Panx1 in regulation of peritoneal cell population and peritonitis development.
Animals ; Carrier Proteins ; metabolism ; Cell Line ; Connexins ; antagonists & inhibitors ; deficiency ; genetics ; metabolism ; HEK293 Cells ; Humans ; Inflammasomes ; metabolism ; Macrophages ; cytology ; metabolism ; Mice ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nerve Tissue Proteins ; antagonists & inhibitors ; deficiency ; genetics ; metabolism ; Peritoneal Cavity ; cytology ; Peritonitis ; chemically induced ; metabolism ; pathology ; RNA Interference ; RNA, Small Interfering ; metabolism ; Thioglycolates ; toxicity

OBJECTIVE To explore the impact of the adjustment of the national reimbursement drug list on rare disease drugs in hospitals， and to provide reference for improving the drug security of patients with rare diseases in China.METHODS The monthly procurement data of rare disease drugs from 789 medical institutions that continuously reported data from January 2016 to December 2018 were extracted from the Chinese Medicine Economic Information. The single-group interrupted time series model was used to compare drug varieties， procurement amount， average defined daily cost （DDDc） and defined daily doses （DDDs） of rare disease drugs before and after the adjustment of national reimbursement drug list. RESULTS In 2017， a total of 9 rare disease drugs were newly included in the national reimbursement drug list， including pirfenidone， carbidopa/levodopa， riluzole， ropinirole， droxidopa， ezetimibe， everolimus， coagulation factor Ⅸ human recombinant and coagulation factor Ⅶa human recombinant. After the adjustment of the national reimbursement drug list， the average DDDc of 9 rare disease drugs was significantly decreased， the upward trend of DDDs and the procurement amount was significantly increased （P＜0.001）. CONCLUSIONS The number of newly included rare disease drugs in national reimbursement drug list keeps increasing， the coverage of medical security keeps expanding， the price of rare disease drugs is significantly decreased， the economic burden of patients is further decreased， and the consumption of rare disease drugs is significantly increased， benefiting more patients with rare diseases； but at the same time， it also increases the procurement amount of rare disease drugs in hospitals. National medical security departments need to fully consider how to balance the affordability of medical insurance funds with the demand for rare disease drug coverage.

Objective: To explore the method of relieving intestinal obstruction in patients with recurrent cervical cancer accompanied with intestinal obstruction after radical radiotherapy. Methods: The data of 10 recurrent cervical cancer patients accompanied with high risk weak constitution and intestinal obstruction after radical radiotherapy from May 2012 to May 2018 were retrospectively analyzed, including preoperative radiotherapy dose, physique and obstruction status, operation time, operation blood loss, postoperative digestive tract patency and diet. All of the 10 patients with cervical cancer recurrence accompanied with intestinal obstruction and disturbance of independent walking after radical radiotherapy. Results: The median fasting time of the 10 patients was 21 days, the median weight was 35.5 kg, the median body mass index (BMI) was 13.3 kg/m^2, the median value of hemoglobin was 67 g/L, and the median value of platelet was 44×10⁹ /L. All of the patients underwent enterostomy. the median operation time was 6.0 min and the median amount of bleeding was 5.0 ml. All of the patients defecated after operation, fed on the first day after operation, and were able to walk on their own 5 days after operation. Conclusions Although the cervical cancer patients with recurrent intestinal obstruction after radical radiotherapy are extremely weak, some patients still have the opportunity to relieve intestinal obstruction if the treatment strategy and surgical method are appropriate.