Objective To observe the protective effects of FTY720 on the Con A-induced mouse hepatic fibrosis injury,and to find the possible mechanisms of protective effects.Methods The pathologic models of hepatic fibrosis injury in the mice caused by Con A were set up.Forty mice were randomly divided into control group, model group,high dose of FTY720 (4 mg·kg-1 )group and low dose of FTY720 (1 mg·kg-1 )dose group (n=10).The serum alanine aminotransferase (ALT)and asparate aminotransferase (AST)activities,hepatic index and pathological changes of hepatic tissue were detected .Results Compared with model group,the serum ALT and AST activities in low and high doses of FTY720 groups were decreased significantly (P < 0.05 or P < 0.01).The optical microscope results showed that there were inflammatory cells and hepatocellular necrosis in model group. The masson staining results showed that there were surrounding fiber bundle and hepatic lobule fusion in model group;compared with model group,the damage degree in low and high doses of FTY720 groups was reduced.The protective effects of FTY720 on hepatic injury showed linear relation to the drug dose.Conclusion FTY720 could decrease the levels of ALT/AST,thus FTY720 alleviate hepatic damage degree and delay the process of hepatic fibrosis.The protective effects of FTY720 on hepatic injury in experimental hepatic fibrosis mice may be related to the mechanisms mentioned above.

Objective To study the damage effect of oxidized low density lipoprotein (OX-LDL)on the endothelial cells and its influence in the expressions of Toll like receptor 4 (TLR-4)and epithelial cell adhesion molecule (EpCAM).Methods The human endothelial cells ECV-304 were cultured in vitro and treated by different concentrations of OX-LDL for 24 h,and the cell vitality was measured by Taipan blue rejection test.The reactive oxygen species (ROS)level,mitochondrial membrane potential (MMP),cell cycle and apoptosis were detected by flow cytometry (FCM).The expression of TLR-4 and EpCAM were also analyzed by FCM.Results Compared with control group,the ROS levels in ECV-304 cells in 25,50,100,and 200 mg·L-1 OX-LDL were increased, but the cell vitalities and MMP were decreased (P < 0.05).Compared with control group,the percentages of S phase cells in 25 and 50 mg·L-1 OX-LDL groups were increased,the G0 G1 phase cells were slightly reduced,and the SubG1 phase cells (apoptotic cells)were increased with the increasing of OX-LDL concentration.Compared with control group,the TLR-4 and EpCAM expression levels in ECV-304 cells in 50 mg·L-1 OX-LDL group at 24 h were significantly increased (P < 0.05 ). Conclusion OX-LDL could increase the ROS level and induce the apoptosis in vascular endothelial cells,while increase the cell vitality and MMP.During the damage process,the expresion levels of TLR-4 and EpCAM are up-regulated.

Fresh healthy human erythrocytes were treated by four kinds of bile acid solutions (DC, GDC, C, and GC) at physiological and pathological concentrations of human plasma, and the membrane proteins, enzyme activities and permeability of cations were observed. The results showed that some components of the membrane cytoskeleton proteins disappeared, the activities of total ATPase and Gr-ATPase were distinctly increased with the increasing of bile acid concentrations, the activity of the membrane acetylcholinesterase was decreased with the increasing bile acid concentrations, the permeability of cations was increased with the increasing bile acid concentrations. The effect of the dihydroxy bile acids more stronger than that of the trihydroxy bile acids.

To establish an HPLC method to determine osimertinib mesylate,Agilent ZORBAX Eclipse Plus C18 column (4.6 mm × 250 mm,5 μm) was used with a mobile phase consisting of methanol-buffer solution (20 mmoL/L NaH2PO4,pH 3.0 adjusted with 85％ H3PO4) (50 ∶ 50) at the flow rate of 1.0 mL/min.The detection wavelength was 210 nm,and the column temperature was kept at 35 ℃.The calibration curve was liner over the range from 50％ to 150％ of determination concentration (0.201 1-0.603 2 mg/mL,r =0.999 9).The limit of quantitation (LOQ) and limit of detection (LOD) were 0.32 μg/mL and 0.08 μg/mL,respectively.The contents of osimertinib mesylate in samples were 100.1％,99.5％ and 99.7％.Good chromatographic separation of osimertinib mesylate and its related substances,including synthetic impurities and degradation products,were obtained.The established HPLC method is specific,accurate,simple and durable,and could be used for the determination of osimertinib mesylate.

AIM: To investigate the changes of the redox status and the antioxidative capability in the tissue of malignant tumors. METHODS: The carcinoma tissues collected from 42 patients with primary cancer in digestive tract (13 cases of esophageal cancer, 14 cases of gastric cancer and 15 cases of colorectal cancer),the corresponding paratumor mucosa tissues were taken as the control samples. The content of oxidized and reduced glutathion (GSSG and GSH), oxidized and reduced coenzyme II (NADP+ and NADPH) were measured, the GSH/GSSG, NADPH/NADP+ ratios, and the GSH/GSSG, NADPH/NADP+ redox potentials were calculated according to Nernst formula. RESULTS: The levels of GSH and NADPH in cancer tissues were significantly higher than those in corresponding paratumor tissues (P0.05). CONCLUSIONS: The significant increase in GSH and NADPH contents in cancer tissues indicates a notable enhancement of its antioxidative capability compared with the corresponding paratumor tissues. Based on this changes, the redox potential in the cancer tissues has only slightly reductive shift, which may suggest an apparent oxidative stress existed in the cancer tissues.

Objective To study the apoptosis of K562 cells induced by a new immunosuppressive agent FTY720 and its mechanism,and to provide experimental basis for the treatment of leukemia in clinic.Methods The K562 cells were cultured in vitro and divided into blank control group and FTY720 treatment group.The K562 cells in FTY720 treatment group were treated with 6μmol·L-1 FTY720 for 3,6,and 12 h,or treated with different concentrations of FTY720 (2,4,6,8μmol·L-1)for 24 h.The apoptosis,level of reactive oxygen species (ROS),mitochondrial membrane potential(MMP)and cell cycle were measured by flow cytometry.The inhibitory rate of proliferation of K562 cells after treated with FTY720 was detected by WST-1 reducting assay.Results The results of flow cytometry showed that the percentages of apoptotic cells were increased after treated with 6μmol·L-1 FTY720 for 3,6,and 12 h with the prolongation of time compared with blank control group(P<0.01).The percentages of apoptotic cells were also increased after treated with different concentrations of FTY720 for 24 h compared with blank control group(P<0.01).Compared with blank control group,the ROS levels were increased with the increasing of FTY720 concentration,while the MMP was decreased(P<0.01).Compared with blank control group,the percentage of cells at G0/G1 phase was increased,while those at S and G2/M phases were decreased with the increasing of FTY720 concentration (P<0.05).The WST-1 reduction assay results indicated that the inhibitory rates of proliferation of K562 cells after treated with 2,4,6,and 8μmol·L-1 FTY720 for 72 h were (24.0±4.1)%,(46.4±3.9)%,(67.0±4.8)%,and (88.2±5.6)%,respectively,compared with blank control group.The concentration of FTY720 to result the inhibitory rate of 50% (IC50 )on K562 cells was 5.5μmol·L-1 .Conclusion FTY720 could inhibit the proliferation of K562 cells by blocking cell cycle and inducing apoptosis through provoking ROS.

Background: The dietary agent sulforaphane (SFN) has been reported to reduce diabetes-induced renal fibrosis, as well as inhibit histone deacetylase (HDAC) activity. Bone morphologic protein 7 (BMP-7) has been shown to reduce renal fibrosis induced by transforming growth factor-beta1. The aim of this study was to investigate the epigenetic effect of SFN on BMP-7 expression in diabetes-induced renal fibrosis. Methods: Streptozotocin (STZ)-induced diabetic mice and age-matched controls were subcutaneously injected with SFN or vehicle for 4 months to measure the in vivo effects of SFN on the kidneys. The human renal proximal tubular (HK11) cell line was used to mimic diabetic conditions in vitro. HK11 cells were transfected to over-express HDAC2 and treated with high glucose/palmitate (HG/Pal) to explore the epigenetic modulation of BMP-7 in SFN-mediated protection against HG/Pal-induced renal fibrosis. Results: SFN significantly attenuated diabetes-induced renal fibrosis in vivo. Among all of the HDACs we detected, HDAC2 activity was markedly elevated in the STZ-induced diabetic kidneys and HG/Pal-treated HK11 cells. SFN inhibited the diabetes-induced increase in HDAC2 activity which was associated with histone acetylation and transcriptional activation of the BMP-7 promoter. HDAC2 over-expression reduced BMP-7 expression and abolished the SFN-mediated protection against HG/Pal-induced fibrosis in vitro. Conclusion Our study demonstrates that the HDAC inhibitor SFN protects against diabetes-induced renal fibrosis through epigenetic up-regulation of BMP-7.

Andrographis paniculata is a traditional Chinese herbal medicine with a wide cultivation in south China. The market demand has been increasing steadily in recent years. However, there are problems such as disordered production, pesticide residues and heavy metal content in the process of Andrographis paniculata production. Pollution- free cultivation is an effective strategy to solve this problem, and it is also the development direction of the Chinese herbal medicine planting industry at this stage. In order to guide the cultivation of pollution-free and high-quality Andrographis paniculata, this study established a pollution- free fine cultivation technology system of Andrographis paniculata including precise cultivation and site selection. In addition, soil improvement, scientific pollution-free planting mode and high- efficiency integrated pest control technology help solve problems such as pesticide residues and heavy metal content. This paper provides a reference for the pollution-free and fine cultivation of Andrographis paniculata.

Objective To identify the risk factors of prolonged mechanical ventilation (PMV) after lung transplantation. Methods Clinical data of 90 recipients undergoing lung transplantation were retrospectively analyzed. According to the duration of invasive mechanical ventilation after operation, all recipients were divided into the PMV group (ventilation duration > 48 h, n=30) and control group (ventilation duration≤48 h, n=60). Perioperative parameters were compared between two groups, including preoperative parameters [serum creatinine, estimated glomerular filtration rate (eGFR)], intraoperative parameters (cold ischemia time of donor lung, blood loss), and postoperative parameters [the first red blood cell, white blood cell, platelet count, hemoglobin, C-reactive protein, serum creatinine, total bilirubin, alanine aminotransferase (ALT), oxygenation index, eGFR and the mean arterial pressure in intensive care unit (ICU)]. The risk factors of PMV after lung transplantation were assessed by multivariate logistic regression analysis. Results Preoperative serum creatinine level in the PMV group was 62 (53, 67) μmol/L, significantly higher than 57 (47, 62) μmol/L in the control group. Preoperative eGFR in the PMV group was 97 (93, 107) mL/min, significantly lower than 106 (102, 116) mL/min in the control group. The first postoperative oxygenation index in the PMV group was 196 (157, 286) mmHg, significantly lower than 250 (199, 354) mmHg in the control group (all P < 0.05). Multivariate analysis showed that the first increase of postoperative total bilirubin, the first decrease of postoperative oxygenation index and preoperative eGFR decrease were the independent risk factors for PMV following lung transplantation. Conclusions The first increase of postoperative total bilirubin, the first decrease of postoperative oxygenation index and preoperative eGFR decrease are the independent risk factors for PMV after lung transplantation.

Objective:To observe the impacts of different postures on the hemodynamics of lower extremity vein.Methods:In this single center non-randomized controlled study in 15 healthy female volunteers, the hemodynamic changes in the common femoral vein were detected by color Doppler ultrasound at 10 different postures: supine position, slope positions with bed end elevated at 15°, 30° and 45°, trapezoidal positions with bed end elevated at 15°, 30° and 45°, and positions with bed head elevated at 30°, 45° and 60°.Results:Different postures resulted in significant differences in the velocity of blood flow in the common femoral vein ( P<0.05), with slope position at 45°> slope position at 30°> slope position at 15° = trapezoidal position at 30°> trapezoidal position at 15° = trapezoidal position at 45°> supine position> position with bed head elevated at 30°> position with bed head elevated at 45° = position with bed head elevated at 60°. Conclusions:In the postures observed in this study, the slope position with bed end elevated at 45° can promote the most effectively the blood reflux in the lower extremity vein, the trapezoidal positions with bed end elevated may not facilitate the distal blood reflux in the lower extremity vein, and positions with bed head elevated may hinder the blood reflux in the lower extremity vein.