Influenza is a major threat to millions of people worldwide. Vaccines and antiviral agents are two main options available to reduce the impact of the influenza virus, while anti-influenza agents are the most effective means to prevent the transmission of the highly contagious virus and to treat the epidemics of disease. At present, four anti-influenza agents have been approved by the FDA for the treatment of influenza, including two M2 protein ion channel inhibitors-amantadine and rimantadine and two neuraminidase inhibitors-zanamivir and oseltamivir. Arbidol hydrochloride, launched in Russia, is a potent inhibitor of influenza virus, too. Neuraminidase inhibitors could be classified generally by structure into six different kinds: sialic acid derivatives, benzoic acid derivatives, cyclohexene derivatives, cyclopentane derivatives, pyrrolidine derivatives and natural products. In this paper, recent progress in the research of the action mechanisms and structure-activity relationships of these anti-influenza virus agents were reviewed.

In this study,a series of new sildenafil analogues 11-27 possessing a guanidine group were synthesized to investigate their PDE5 inhibitory activity and selectivity using[~3H]cGMP SPA kit in vitro and efficacy in the rat model of erection.Most of the compounds showed potent activity against PDE5,and more importantly,several compounds exhibited higher PDE5 selectivity over PDE6 than that of sildenafil.Structure-activity relationship of these sildenafil analogues was also discussed.Within this series of compounds,compound 15(IC_(50) =1.7 nmol/L)not only exhibited more potent PDE5 inhibitory activity than that of sildenafil (IC_(50) = 6.5 nmol/L),but also showed functional efficacy in the rat model of erection.

OBJECTIVETo investigate role of exocrine cells in the pancreatic enhancement images at Manganese (II) N, N'-dipyridoxylethlenediamine-N, N'-diacetate 5, 5'-bisc (Mn-DPDP)-enhanced magnetic resonance (MR) imaging.

METHODSArtificial pancreatic leakage was constructed in six dogs using a fistula tube inserted into the duodenum papillae. Pancreatic juice was collected before and after intravenous infusion of 2 ml/kg of Mn-DPDP at a rate of 2 - 3 ml/min. The Mn content of pancreatic juice was measured by atomic absorption spectroscopy. T(1)-weighted spin-echo images and T(1)-weighted spoiled phase gradient-echo (SPGR) images were obtained prior and approximately 30 min after the administration of Mn-DPDP at 1.5T.

RESULTSThe Mn content of pancreatic secretion increased 60.47 +/- 21.83 micro g/dl after the administration of Mn-DPDP (t = 6.785, P < 0.01). The signal/noise ratio (S/N) of the pancreas increased 53 percent +/- 49 percent and 62 percent +/- 44% on T(1)W spin echo images and SPGR images, respectively.

CONCLUSIONSExocrine cells of the pancreas can absorb manganese and excrete it through the pancreatic juice. Exocrine cells play an important role in the enhancement of the pancreas in MR imaging with Mn-DPDP.

Animals ; Contrast Media ; Dogs ; Edetic Acid ; analogs & derivatives ; pharmacokinetics ; Image Enhancement ; Magnetic Resonance Imaging ; Manganese ; pharmacokinetics ; Pancreas ; anatomy & histology ; metabolism ; Pyridoxal Phosphate ; analogs & derivatives ; pharmacokinetics

Objective To explore the clinical efficacy and safety of hyper-early embolotherapy in treatment of intracranial ruptured aneurysm.Methods A retrospective analysis was made on 33 patients with intracranial ruptured aneurysm.Preoperative Hunt-Hess grade:grade Ⅰ-Ⅱ in 16 patients,gradeⅢin 5 patients,grade Ⅳ in 9 patients,grade Ⅴ in 3 patients.All patients were confirmed with subarachnoid hemorrhage (SAH) by angiography and then underwent embolization under general anesthesia by detachable coils within 6 h from onset.Results After operation,25 patients (75.8％) recovered well,4 patients (12.1％) were with mild disability with paralysis and aphasia,4 patients (12.1％) were dead (1 patient for intraoperative aneurysm rupture,1 patient for postoperative pneumonia,1 patient for infection of hematoma at puncture site and 1 patient for postoperative gastrointestinal bleeding).Followed up 1-6 months,no rebleeding occurred.Conclusions Hyper-early embolotherapy could avoid rebleeding of the aneurysm,and relieve the vasespasm,without increasing the intra-operative rebleeding rate.Moreover hyper-early embolotherapy could greatly decrease the mortality of poor-grade SAH patients.

ObjectiveTo investigate the effect of astragaloside Ⅳ（AS-Ⅳ） on the proliferation of vascular smooth muscle cells（VSMCs） induced by angiotensin Ⅱ（Ang Ⅱ） based on solute carrier family 7 member 11/glutathione peroxidase 4（SLC7A11/GPX4） pathway. MethodsPrimary rat thoracic aortic VSMCs were cultured by tissue explant method， and the cell types were identified by immunofluorescence. Cell counting kit-8（CCK-8） was used to determine the optimal concentration and time of AS-Ⅳ after Ang Ⅱ stimulation. The experiment was divided into blank group， model group， AS-Ⅳ group（40 μmol·L^-1）， Erastin group（0.5 μmol·L^-1）， Erastin+AS-Ⅳ group（0.5 μmol·L^-1+40 μmol·L^-1）. The blank group was cultured in normal medium， the model group was cultured in medium containing Ang Ⅱ（0.1 μmol·L^-1）， and each administration group was cultured in medium containing Ang Ⅱ（0.1 μmol·L^-1） and the corresponding doses of drug. CCK-8 and plate clone formation assay were used to detect the proliferation of cells in each group， Prussian blue staining was used to detect cell iron deposition， the content of reactive oxygen species（ROS） in cells was detected by fluorescence probe method， the content of malondialdehyde（MDA） was detected by thiobarbituric acid（TBA） method， and the protein levels of SLC7A11 and GPX4 in each group were detected by Western blot. ResultsPrimary rat thoracic aortic VSMCs were successfully cultured by tissue explant method， and immunofluorescence detection showed that positive expression of α-smooth muscle actin（α-SMA） and negative expression of vimentin in the cells， identifying them as VSMCs. The optimal concentration and time of AS-Ⅳ determined by CCK-8 were 40 μmol·L^-1 and 24 h， respectively. Pharmacodynamic studies showed that compared with the blank group， the cell proliferation in the model group increased， the iron deposition in the cells increased， the contents of ROS and MDA increased， and the expression levels of SLC7A11 and GPX4 proteins decreased（P<0.05， P<0.01）. Compared with the model group， the cell proliferation of the AS-Ⅳ group was inhibited， the iron deposition in the cells was decreased， the contents of ROS and MDA were decreased， and the expression levels of SLC7A11 and GPX4 proteins were increased（P<0.05， P<0.01）. While in the Erastin group， the cell proliferation was increased， the iron deposition was increased， ROS and MDA contents were increased， and the expression levels of SLC7A11 and GPX4 proteins were decreased（P<0.05， P<0.01）. Compared with the AS-Ⅳ group， Erastin+AS-Ⅳ group showed increased cell proliferation， increased iron deposition in cells， increased ROS and MDA contents， and decreased expression of SLC7A11 and GPX4 proteins（P<0.05）. Compared with the Erastin group， the cell proliferation in Erastin+AS-Ⅳ group was inhibited， the iron deposition was decreased， the contents of ROS and MDA were decreased， and the expression levels of SLC7A11 and GPX4 proteins were increased（P<0.05， P<0.01）. ConclusionAS-Ⅳ can inhibit ferroptosis by regulating the SLC7A11/GPX4 pathway， so as to weaken the proliferation of VSMCs， thus playing a role in the treatment of atherosclerosis.