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Objective:To study the components with urate anion transporter 1（URAT1） regulation effect and their combination mechanisms of Lagotis brevituba by integrating techniques of HK-2 cell capture，UPLC-Q-TOF-MS and molecular docking，so as to provide material and theory bases for the development of new hypouricemic medicines based on L. brevituba. Method:The HK-2 cells were applied to capture the components of L. brevituba. UPLC-Q-TOF-MS was used to identify those components. The molecular docking technique was adopted to study the interaction mechanism between the compounds and URAT1. Result:Eight components were successfully screened and identified as hyperoside，plantamajoside，kaempferol-3-O-glucoside，lugrandoside，nepitrin，isolugrandoside，homoplantaginin，luteolin，respectively. Those components could combine with URAT1 mainly through hydrogen bond，van der Waals force and hydrophobic action，which were closely related to structure and compound types. Furthermore，the LibDock score of phenylethanoids was higher than that of flavonoids. Conclusion:The integration of target cell capture，UPLC-Q-TOF-MS and molecular docking techniques could be successfully used to identify captured compounds of L. brevituba with URAT1 regulation effects and illustrate their potential combination mechanisms as well as the structure-activity relationships. The findings may provide material and theory bases for the development of new hypouricemic medicines based on L. brevituba.
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In aged patients, acute kidney injury (AKI) is a common clinical complication after percutaneous coronary intervention (PCI), highlighting the need for timely and certain diagnosis of this disease. A single centre, nested case-control study was conducted, which assessed the usefulness of urinary liver-type fatty acid-binding protein (uL-FABP), neutrophil gelatinase-associated lipocalin (uNGAL), and kidney injury molecule-1 (uKIM-1) for early detection of AKI. One hundred and thirty-two patients at or over 60 years old undergoing PCI were included. Serum creatinine (SCr) was measured before PCI, 24 and 48 h after PCI; uL-FABP, uNGAL, and uKIM-1 were measured before PCI, 6, 24, and 48 h after PCI. We identified 16 AKI patients and selected 32 control patients matched by admission time (<1 week), age (±5 years), and gender. In the receiver operating characteristic (ROC) curve analysis, the areas under the curve (AUCs) for the relative measurements of uL-FABP, uNGAL, and uKIM-1 were 0.809, 0.867, and 0.512 at 6 h after PCI, and 0.888, 0.840, and 0.676 at 24 h after PCI, respectively. AUC for the combination of uL-FABP and uNGAL was 0.899 at 6 h after PCI, and 0.917 at 24 h after PCI. Thus, measurement of uL-FABP and uNGAL levels at 6 and 24 h after PCI may be useful in detecting AKI in aged patients. Measurement of uKIM-1 levels provides inferior predictive power for early diagnosis of AKI.
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Acute Kidney Injury , Diagnosis , Urine , Early Diagnosis , Fatty Acid-Binding Proteins , Urine , Hepatitis A Virus Cellular Receptor 1 , Lipocalin-2 , Urine , Percutaneous Coronary InterventionABSTRACT
Asthma is a kind of chronic respiratory inflammation, commonly with breathlessness, chest tightness, coughing, recurrent episodes of wheezing and airflow obstruction, severely affecting human health. A variety of immunocytes are involved in this chronic disease. Chinese herbal medicine(CHM) has a long history in the treatment of asthma. A large number of studies have shown that CHM could ameliorate asthma symptoms through regulating cellular immune responses. This paper reviewed the studies of CHM on the regulation of immunocytes and their mechanisms in recent years, including the count of inflammatory cells, maturation of dendritic cells, balance of helper T cell subtypes, induction of regulatory T cells and intracellular signaling pathways. We also proposed the future research directions about the effects of CHM on asthma treatment.
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Objective:To explore anti-platelet/anti-coagulation treatment and their influence on prognosis in advanced aged patients with acute coronary syndrome (ACS)complicated atrial fibrillation (AF)after percutaneous coronary intervention (PCI).Methods:A total of 204 advanced aged ACS + AF patients treated in our heart center were se-lected.All patients received CHA2 DS2 Vasc score assessment,male had score ≥2 scores and female had score ≥3 scores.A total of 160 cases received dual anti-platelet therapy combined anticoagulant treatment of warfarin,and they were randomly divided into low intensity group [n=80,international normalized ratio (INR)remained 1.8~2.3]and high intensity group (n=80,INR remained 2.3~2.8),both groups were followed up for 18 months.Inci-dence rates of major adverse cardiovascular and cerebrovascular events (MACCE),ischemic and hemorrhage events were observed.Results:Both groups were followed up for a mean 18 months,and there were no significant differ-ence in all-cause mortality,incidence rates of MACCE and fatal hemorrhage between two groups,P > 0.05 all.Compared with low intensity group,there were significant rise in incidence rates of severe hemorrhage (3.8% vs. 12.5%),P <0.05.Conclusion:Low intensity warfarin anticoagulant therapy can effectively reduce incidence rates of MACCE and ischemic events,and incidence rate of hemorrhage events is low in advanced aged ACS + AF pa-tients after PCI.
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Objective · To investigate the effects and mechanisms of pregnancy immune tolerance induced by a novel immunosuppressive agent FTY720 and to provide experimental basis for the clinical treatment of unexplained recurrent spontaneous abortion. Methods · The mice of spontaneous abortion model were used as subjects. The effects of intraperitoneal injection of FTY720 on the embryo loss rate in mice of spontaneous abortion model and on the expression of sphingosine-1-phosphate (S1P) in the decidual tissue were observed. S1P-siRNA lentiviral vectors and S1P-overexpression gene lentiviral vectors were constructed and transfected into dendritic cells (DCs) from mouse bone marrow. The effects of FTY720 on the embryo loss rate in mice of spontaneous abortion model after adoptive transferring of these two types of lentiviral vectors were observed. Results · FTY720 had no significant effect on the embryo loss rate in normal pregnant mice. Intraperitoneal injection of FTY720 significantly reduced the embryo loss rate in mice of spontaneous abortion model. The expression of S1P in the decidual tissue in mice of spontaneous abortion model was low. After adoptive transferring of S1P-siRNA lentiviral vector transfected DCs, FTY720 could slightly reduce the embryo loss rate in mice of abortion mouse model, but the effect was far less than that of before adoptive transferring of S1P-siRNA lentivirus transfected DCs. After adoptive transferring of the S1P-overexpression gene lentiviral vector transfected DCs, FTY720 could significantly reduce the rate of embryo loss in mice of spontaneous abortion model and the effect was more significant than that of before adoptive transfecting of S1P-overexpression lentiviral vector transfected DCs. Conclusion · FTY720 is safe. The induction of pregnancy immune tolerance may be related to the blockage of S1P signaling pathway.
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Objective:To explore anti-platelet/anti-coagulation treatment and their influence on prognosis in advanced aged patients with acute coronary syndrome (ACS)complicated atrial fibrillation (AF)after percutaneous coronary intervention (PCI).Methods:A total of 204 advanced aged ACS + AF patients treated in our heart center were se-lected.All patients received CHA2 DS2 Vasc score assessment,male had score ≥2 scores and female had score ≥3 scores.A total of 160 cases received dual anti-platelet therapy combined anticoagulant treatment of warfarin,and they were randomly divided into low intensity group [n=80,international normalized ratio (INR)remained 1.8~2.3]and high intensity group (n=80,INR remained 2.3~2.8),both groups were followed up for 18 months.Inci-dence rates of major adverse cardiovascular and cerebrovascular events (MACCE),ischemic and hemorrhage events were observed.Results:Both groups were followed up for a mean 18 months,and there were no significant differ-ence in all-cause mortality,incidence rates of MACCE and fatal hemorrhage between two groups,P > 0.05 all.Compared with low intensity group,there were significant rise in incidence rates of severe hemorrhage (3.8% vs. 12.5%),P <0.05.Conclusion:Low intensity warfarin anticoagulant therapy can effectively reduce incidence rates of MACCE and ischemic events,and incidence rate of hemorrhage events is low in advanced aged ACS + AF pa-tients after PCI.
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Objective · To investigate the effects and mechanisms of pregnancy immune tolerance induced by a novel immunosuppressive agent FTY720 and to provide experimental basis for the clinical treatment of unexplained recurrent spontaneous abortion. Methods · The mice of spontaneous abortion model were used as subjects. The effects of intraperitoneal injection of FTY720 on the embryo loss rate in mice of spontaneous abortion model and on the expression of sphingosine-1-phosphate (S1P) in the decidual tissue were observed. S1P-siRNA lentiviral vectors and S1P-overexpression gene lentiviral vectors were constructed and transfected into dendritic cells (DCs) from mouse bone marrow. The effects of FTY720 on the embryo loss rate in mice of spontaneous abortion model after adoptive transferring of these two types of lentiviral vectors were observed. Results · FTY720 had no significant effect on the embryo loss rate in normal pregnant mice. Intraperitoneal injection of FTY720 significantly reduced the embryo loss rate in mice of spontaneous abortion model. The expression of S1P in the decidual tissue in mice of spontaneous abortion model was low. After adoptive transferring of S1P-siRNA lentiviral vector transfected DCs, FTY720 could slightly reduce the embryo loss rate in mice of abortion mouse model, but the effect was far less than that of before adoptive transferring of S1P-siRNA lentivirus transfected DCs. After adoptive transferring of the S1P-overexpression gene lentiviral vector transfected DCs, FTY720 could significantly reduce the rate of embryo loss in mice of spontaneous abortion model and the effect was more significant than that of before adoptive transfecting of S1P-overexpression lentiviral vector transfected DCs. Conclusion · FTY720 is safe. The induction of pregnancy immune tolerance may be related to the blockage of S1P signaling pathway.
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Purpose To investigate the expression of vasculogenic mimicry (VM) and hypoxia inducible factor-1 α (HIF-1α),cathepsin D (CTSD) in esophageal squamous cell carcinoma (ESCC) and its relationship with clinicopathological parameters.Methods 120 specimens of primary ESCC and their clinical data were collected.Dual staining of CD34 and PAS were performed to validate the existence of VM in ESCC.Immunohistochemical of EnVision two-step method was used to detect the expression of VM-related markers vascular endothelial cadherin (VE-cadherin) and vascular endothelial grow factor (VEGF),HIF-1α and CTSD in 120 cases of ESCC.The relationship between HIF-1α,CTSD and clinical pathological parameters were analyzed.Results The positive rate of HIF-1α,CTSD was correlated with infilatrating,lymph node metastasis,clinical stage and cancer embolus.VM existed in 25 of 120 cases.The expression of HIF-1α and CTSD in cases with VM was obviously higher than that without VM,the expression of HIF-1 α and CTSD was positively correlated with VM in ESCC.The expression of CTSD in case with HIF-1 α was obviously lower than that without HIF-1α,the expression of CTSD was positively correlated with HIF-1α in ESCC.The expression of VE-cadherin and VEGF in cases with CTSD was obviously higher than that without CTSD,the level of VE-cadherin and VEGF expression was positively correlated with CTSD in ESCC.Conclusion CTSD may promote VM formation in ESCC via HIF-1α.High expression of HIF-1α and CTSD indicate poor prognosis of ESCC patients.