Objective To investigate the effect and its mechanism of cyclin dependent protein kinase inhibitor Olomoucine treatment on experimental herpes simplex encephalitis(HSE). Methods 45 mice were randomly assigned to HSV-1 sham-infected group (n=15), HSV-1 infected control group (n=15) and Olomoucine treated group (n=15). Flow cytometry was used to detect the expression of brain cells surface antigen CD11b. The reverse transcription polymerase chain reaction (RT-PCR) to detect the expression of tumor necrosis factor-? (TNF-?) and Interleukin-6 (IL-6). TUNEL method was adopted to detect neural cells apoptosis. Pathologic slices of brain tissues were used to identify tissue morphology differences. The survival rates were compared between the treatment groups Acyclovir (n=20) and Olomoucine (n=20) by the method of Kaplan-Meier 2 weeks after HSV-1 infection. Results After HSV-1 infection, the expression of brain tissue CD11b, TNF-?, IL-6 were significantly increased compared with sham-infected group (allP

Cell Line ; Glucocorticoids ; pharmacology ; HSP90 Heat-Shock Proteins ; metabolism ; Humans ; Mucin 5AC ; metabolism ; Respiratory System ; drug effects ; metabolism

ProTide technology is a kind of prodrug design strategy invented by the team of Christopher McGuigan. ProTides are aryloxyphosphoramidates (or aryloxyphosphonamidates) which contain a phosphorus atom combined with an amino acid ester and an aryloxy group. These prodrugs can efficiently cross the cell membrane and escape from the first rate-limiting step of phosphorylation, which afford effective solutions to the drawbacks of current nucleoside analogues. At present, ProTide technology has been extensively applied in the field of antiviral research. It has been successful in providing a number of approved drugs and clinical candidates, such as sofosbuvir and so much more, highlighting the promising future in drug discovery. This review summarizes the brief history and characteristics of ProTide technology, as well as its application in the exploration of antiviral drugs.

AIM: To investigate the effect of human amniotic fluid on the release of thromboxane A 2 (TXA 2), prostaglandin I 2 (PGI 2) and Leukotriene C 4(LTC 4) from blood cells. METHODS: 1 mL human amniotic fluid and 10 mL oneself blood collected from 38-41 weeks with cesarean section were cultured at 37℃ for 30 min, and then centrifuged. The supernatants were taken and stored at -70℃. TXB 2 and 6-Keto-PGF 1? of the superntants were determined by radioimmunoassay and LTC 4 by enzyme immunoassay. RESULTS: It was found that the levels of TXB 2 and LTC 4 in blood were elevated from (63.5?52.0) ng/L and (40.1?39.2) ng/L to (189.1?102.0) ng/L and (293.5?206.1) ng/L respectively (P0.05).CONCLUSION: Amniotic fluid might stimulate the release of TXA 2 and LTC 4 from blood, it might affect the balance of TXA 2 and PGI 2 in blood, which might play an important role in the pathogenesis of amniotic fluid embolism.

Objective To investigate the expression of HIF-1α protein in the placenta bed and the concentration of von Willrand factor (vWF) in maternal peripheral blood from pre-eclampsia and normal pregnancy, and to determine the effect of HIF-1α and vWF on the pathogenesis of pre-eclampsia. Methods Forty pre-eclampsia patients (20 mild and 20 severe) were recruited as 2 study groups, and another 20 normal pregnant women were served as a normal group.Western blot was used to detect the expression of HIF-1α protein in the placenta bed. ELISA was adopted to detect the concentration of vWF in the maternal peripheral blood.Correlation between HIF-1α protein expression and vWF level was analyzed by Spearman method.Results The expression of HIF-1α protein in the placenta bed was the highest in the severe pre-eclampsia patients among 3 groups, followed by the mild pre-eclampsia patients and the normal controls.There was significant difference (among) 3 groups (P＜0.001).The concentration of vWF in the maternal peripheral blood was the highest in the severe pre-eclampsia patients, followed by the mild pre-eclampsia patients and the normal controls.There was significant difference among the 3 groups (P＜0.05). Postive correlation was found between the expression of HIF-1α protein in the placenta bed and the concentration of vWF in the maternal peripheral blood in patients with pre-eclampsia (r_1=(0.65,) P＜(0.001)),and between the concentration of vWF in the maternal peripheral blood and the pathogenetic condition degree of pre-eclampsia (r_2=(0.61,)P＜0.001).Conclusion HIF-1α in coordination with vWF may play an important role in the pathogenesis of pre-eclampsia.

Objective To investigate the possible mechanism of endonuclease G (Endo G)-mediated non-Caspase-dependent apoptotic pathway in brain neuronal apoptosis in chronic fluorosis rats.Methods Sixty Sprague Dawley (SD) rats (half male and half female) were randomly divided into two groups:control group fed with tap water with fluoride content ＜ 0.5 mg/L and fluorine group in which sodium fluoride was added into drinking water with fluoride content of 50.0 mg/L.Both groups were fed with standard food with fluorine content ＜ 0.5 mg/kg.The experiment period was 10 months.At the end of the experiment,all the animals were sacrificed,and brain tissue was taken.Flow cytometry was used to examine apoptosis rate,immune-histochemistry was employed to detect the distribution of Endo G in brain tissue;Western blotting was used to test the protein expression of Endo G.Results Compared to the apoptosis rate of control group [(1.3 ± 0.6)％,(1.9 ± 0.3)％],the apoptosis rate in hippocampus and cortex of rats with chronic fluorosis [(2.6 ± 0.6)％,(3.1-± 0.7)％] was significantly increased (t =3.1,3.4,all P ＜ 0.05).The Endo G positive neurons and their degree of staining in CA1,CA2,CA3 and CA4 of hippocampus,frontal cortex as well as the upper layer of parietal cortex [(11.1 ± 2.2),(10.2 ± 1.9),(9.8 ± 3.1),(9.9 ± 1.6),(10.6 ± 2.9),(8.2 ± 2.4),(11.1 ± 2.8) scores] in rats with chronic fluorosis were significantly higher than those in the control group [(5.8 ± 1.8),(6.7 ± 2.6),(5.2 ± 2.4),(7.2 ± 2.1),(7.7 ± 2.6),(6.1 ± 1.9),(8.1 ± 2.6) scores,t =2.9,2.5,2.4,2.3,2.2,2.5,2.3,P ＜ 0.01 or ＜ 0.05].The protein level of Endo G in the mitochondria of rat brains with chronic fluorosis [(86.4 ± 7.2)％,(83.9 ± 6.8)％] was significantly lower than that of control group [(100.0 ± 6.1)％,(100.0 ± 5.5)％,t =2.6,2.3,all P ＜ 0.05].Meanwhile,the protein level of Endo G in the nucleus of neurons from chronic fluorosis rats [(117.5 ± 6.4)％,(115.2 ± 6.2)％] was significantly higher than that of the control [(100.0 ± 5.2)％,(100.0 ± 5.5)％,t =2.5,2.2,all P ＜ 0.05].Conclusion The high expression of Endo G and nuclear transfer are related to the neuron apoptosis in chronic fluorosis rat,which may be one of the mechanisms of brain injury of the disease.

Objective To compare the rates of major adverse cardiovascular events(MACE)and bleeding events of three different antiplatelet strategies during temporary withdrawal of antiplatelet therapy for non-cardiac surgery within 1 year after drug-eluting stent (DES)implantation.Methods Retrospectively analyzed 42 patients who had accepted non-cardiac surgery and required temporary withdrawal of antiplatelet therapy within 1 year after drug-eluting stent implantation. The patients were divided into three groups according to the bridging antiplatelet strategies they received.All patients discontinued clopidogrel 5 to 7 days before the non-cardiac surgery. The tirofiban group was treated with intravenous tirofiban 0.4ug/kg·min in the first 30 min followed 0.1μg/(kg·min). The dosage was reduced by half for patients whose Creatinine clearance were less than 30 ml/min.The low molecular weight heparin group was treated with subcutaneous enoxaparin (Clexane 4000 AxaIU, once per day) .The asprin group was given only oral asprin(100 mg, once per day) . Tirofiban and low molecular weight heparin were continued until clopidogrel was resured. Perioperative cardiovascular events and serious bleeding were recorded. Results The rates of major adverse cardiac events in the tirofiban and the low molecular weight heparin group were lower than the aspirin group. Acute myocardial infarction caused by confirmed in-stent thrombosis was diagnosed in one patient in the aspirin group. One case of asymptomatic ST-T changes was found in the low molecular weight the aspirin group. 3 cases in the aspirin group presented ST-T changes on ECG and among them 1 case was STEMI due to LAD thrombosis requiring primary and 2 other cases were agina pectoris.There were no significant differences in bleeding events among the three groups.Conclusions Potential for the perioperative management with tirofiban or low molecular weight heparin is safe and feasible for patients who had recently undergone DES implantation and required noncardiac surgery with the interruption of antiplatelet therapies.

Objective To observe the effect of exhaustive exercise on the function of the kidney in rats and explore the mechanism. Methods Fourteen male Sprague-Dawley rats were divided into sedentary control group (group C) and exhaustive exercise group (group E). They were measured the urine protein, uric acid, glucose, and blood urea nitrogen after exercise. The reactive oxygen species, inducible ni-tric oxide synthase, nitro tyrosine in kidney, and nephrin protein in the kidney were detected with fluorescent probe and Western blotting, re-spectively, and observed under Harris staining. Results There were significant differences between groups C and E in urine protein, uric ac-id, glucose, blood urea nitrogen, reactive oxygen species, inducible nitric oxide synthase, nitrotyrosine and nephrin protein (P<0.05). The glomerular morphology and the deformation of capillary basement membrane were found under the fluorescence microscope in group E. Conclusion Exhaustive exercise may damage the structure of kidney in rats, which may associate with oxidative stress.

Objective To investigate the risk factors and prognosis of perioperative myocardial infarction in the patients undergoing noncardiac surgery. Methods Clinical data of 562 patients who had accepted non-cardiac surgery was collected and retrospectively analyzed. The risk factors, treatments and outcomes of all these patients were recorded and analyzed. Results A total of 19 out of the 562 patients had perioperative myocardial infarction ( PMI) . The incidence was 3. 4% . The mean occurrence time was (43. 5 ± 12. 7)h after operation. Eleven PMI patients (11 ∕ 19) were non-ST-segment elevation myocardial infarction and eight patients (8 ∕ 19) were ST-segment elevation myocardial infarction. Thirteen PMI patients were left coronary artery occlusion and six patients were right coronary artery occlusion. Advanced age, history of myocardial infarction, unstable angina, change of ST-T segment on electrocardiography (ECG), multivessel diseases, diabetes,hypertension,and high risk non-cardiac surgery were the risk factors of PMI and positively correlated to PMI. Sixteen PMI (16 ∕ 19) patients accepted PCI treatment and three patients (3 ∕ 19) accepted drug conservative treatment. Two patients had unstable angina attack after treatment and one patient had arrhythmia. The heart function in two patients decreased by one or more than one class within the follow up of 1 year. No patient had recurrent acute myocardial infarction or deceased during follow-up. Conclusions Many factors could lead to PMI. Making preoperative assessment, recognizing patients of high risks and dealing with patients who had PMI in time was necessary.

Objective To investigate the distribution modes of NOS nerves and interstitial cells of Cajal (ICCs) in myenteric plexus of human fetal intestine. Methods Small intestine samples from 12 fetuses were collected for the preparation of whole mount preparations and cryo sections examined by immunocytochemistry for c kit receptor tyrosine kinase and histochemistry for NADPH diaphorase. Results ICCs associated with the myenteric plexus in the fetal small intestine were observed in the shape of spindle or ovoid with two to three slender processes forming an independent and complete cellular network. While NOS positive nerves, which constitute the main neuronal component of ganglia, connecting strands, and nerve fibers, were found within the circular muscle layer and myenteric plexus of the small intestine and the latter was especially rich of this kind of nerves. Most of these positive neurons were Dogiel I type neurons and they often gathered in cluster in the ganglia. Each ganglion contained several to dozens of NOS positive neurons. Although no colocalization of ICCs and NOS positive nerves was found by double staining of whole mount preparations and cryo sections, they were closely distributed. Conclusion Our results indicate that NO released by myenteric plexus, an inhibitory neurotransmitter, may possess the function of regulating ICCs and smooth muscle in late stage of the fetus.