Obstructive sleep apnea (OSA),the most common type of sleep disordered breathing was closely associated with the occurrence of ischemic stroke.It has been demonstrated that OSA is an independent risk factor for ischemic stroke.Its pathogenic mechanism includes atherosclerosis,coagulation abnormalities and cerebral hemodynamic changes caused by long-term periodic hypoxia hypoxemia and hypercapnia.The prognosis of ischemic stroke patients with OSA is poor.Therefore,it needs to be treated early to avoid further damage to brain tissue and reduce the mortality.

Bioisosterism is one of the most common strategies in drug structure optimization. With the development of medicinal and organic chemistry, more and more classic and non-classical bioisosteres are used in the design of novel drugs. In recent years, fluorinated groups as a bioisostere have been paid more and more attention by pharmaceutical chemists. This paper briefly reviews the physicochemical properties, chemical preparation methods of difluoromethyl (CF₂H) group, and its application in drug design to provide references for drug discovery researchers.

Animals ; Cerebral Cortex ; metabolism ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred Strains ; Morphine Dependence ; metabolism ; Neurotrophin 3 ; metabolism ; Prosencephalon ; metabolism

By Silica gel, Sephadex LH-20 and other materials for isolation and purification and by physicochemical methods and spectral analysis for structural identification, 23 compounds were isolated and identified from ethyl acetate portion of alcohol extract solution of Osmanthus fragrans fruits. Their structures were identified as nicotinamide (1), D-allitol (2), 5-hydroxymethyl-2-furancarboxaldehyde (3), acetyloleanolic acid (4), benzoic acid (5), ergosta-7,22-dien-3-one (6), beta-sitosterol (7), borreriagenin (8), cerevistero (9), c-veratroylglycol (10), methyl-2-O-beta-glucopyranosylbenzoate (11), 3', 7-dihydroxy-4'-methoxyisoflavon (12), umbelliferone (13), caffeic acid methyl ester (14), oleanolic acid (15), (-) -chicanine (16), dillapiol (17), 3beta,5alpha, 9alpha-trihydroxyergosta-7-22-dien-6-one (18), 2alpha-hydroxy-oleanolic acid (19), betulinic acid (20), betulin (21), 3, 3'-bisdemethylpinoresinol (22), and lupeol (23). All compounds were isolated from the osmanthus fruit for the first time. Except for compounds 4, 7, 15, 19, 23, the rest ones were isolated from the this plant for the first time.
Drugs, Chinese Herbal ; chemistry ; Fruit ; chemistry ; Oleaceae ; chemistry

OBJECTIVETo study the blood enriching effects of Paeoniae Radix Rubra and Paeoniae Radix Alba, paeoniflorin and albiflorin on mouse model of blood deficiency caused by γ-ray radiation.

METHODBuild mouse model of blood deficiency induced by γ-ray radiation. Paeoniae Radix Rubra and Paeoniae Radix Alba were given during modeling. The amount of WBC was detected af- ter the treatment. Based on the result of WBC and paeoniflorin content, albiflorin content in Paeoniae Radix Rubra and Paeoniae Radix Alba, the same model and the same method were used to comparatively study the effect of blood enriching of paeoniflorin and albiflorin.

RESULTOn the 7th day, the amount of WBC in model mice treated with 2 g x kg(-1) Paeoniae Radix Alba and 2 g x kg(-1) Paeoniae Radix Rubra significantly increased compared with that of model group (P < 0.05). In another experiment with the same model, the amount of WBC in model mice treated with 120 mg x kg(-1) paeoflorin and 120 mg x kg(-1) albiflorin significantly increased (P < 0.05) compared with that of model group on the 7th day. On the 10th day, the amount of WBC in rats treated with 120 mg x kg(-1) paeoflorin increased significantly (P < 0.05) compared with that of model group. Compared with the same dose of paeoniflorin, the amount of WBC in mice treated with albiflorin had no significant difference.

CONCLUSIONAll Paeoniae Radix Alba, Paeoniae Radix Rubra, paeoniflorin and al- biflorin can raise the amount of WBC and have the effect of enriching blood induced by radiation, while paeoniflorin and albiflorin have a similar result in this model. The result indicated that both paeoniflorin and albiflorin are effective constituents in Paeoniae Radix Alba, and paeoniflorin work as the common effective constituent in both Paeoniae Radix Rubra and Paeoniae Radix Alba.

Animals ; Bridged-Ring Compounds ; pharmacology ; Gamma Rays ; adverse effects ; Glucosides ; pharmacology ; Leukocyte Count ; Leukocytes ; cytology ; drug effects ; radiation effects ; Male ; Mice ; Monoterpenes ; pharmacology ; Rats

Objective To isolate and identify the adult neural stem cells from the parenchyma of spinal cord in adult mouse.Methods The parenchymal spinal cord from adult mouse was dissected and dissociated by mechanical trituration.The tissue suspension was cultured in serum-free DMEM/F12 medium supplemented with EGF and B27.The cell colonies generated from a single cell were screened by limited dilution and incubated with BrdU.The cell colonies were transferred into medium with serum to induce differentiation.The cells were identified with antibodies to Nestin,BrdU,MAP2 and GFAP by immunofluorescence staining.Results The cells were cultured for seven days to generate proliferative neurospheres.The majority of cells in these neurospheres expressed Nestin and were differentiated into MAP2-positive cells and GFAP-positive cells in medium containing with fetal bovine serum.Conclusion A significant number of neural stem cells are present in the parenchymal adult mouse spinal cord and can proliferate and also give rise to neurons and glia in vitro.

Objective To study the follow-up management strategies after improving stoves for controlling coal-burning type endemic fluorosis in Guizhou and to provide a scientific basis for exploring the follow-up management measures.Methods In 2006 - 2009,three counties of Puding,Bijie and Liuzhi with improved stoves in 2005 and implemented follow-up management measures for subsequent three years were chosen,3 towns were chosen randomly in each chosen county,2 villages were selected randomly in each chosen town,10 households were investigated randomly in each chosen village,and 20 students were investigated of the knowledge of fluorosis control.The investigation included also the usage of the stoves,dehydration methods of grain and related conditions.Results ①The head of the family and student awareness of fluorosis control were 82.6％(743/900)and 91.7％ (1650/1800),respectively,and 35.0％ ( 385/1100 ) and 61.0％ (6605/10 835 ),respectively,before the test,and the difference was statistically significant( x2 =33.04,1189.12,all P ＜ 0.01 ).②The rates of chimney out of the house were 88.5％(69/78) and 100.0％(102/102),respectively,compared with those before the trial[74.4％(2125/2856) and 2.1％(104/4984),respectively],the difference was statistically significant(x2 =720.56,4295.38,all P ＜ 0.01).The iron stove and the table stove's airtight utilization rates were 85.9％(67/78) and 100.0％(102/102),respectively.③The corn and the hot pepper's correct drying rates were 100.0％(180/180).Compared with those[27.2％(49/180) and 32.2％(58/180),respectively]before the trial,the difference was statistically significant(x2 =26.68,37.38,all P ＜ 0.01 ).The corn and the hot pepper's washing rates before eating were 95.0％(57/60) and 98.3％(177/180),respectively.Compared with those[85.0％(153/180) and 77.8％(140/180)]before the trial,the difference was statistically significant(x2 =135.00,490.82,all P ＜ 0.01 ).Conclusions The target population's awareness and knowledge of fluorosis prevention and related behavior are significantly elevated and enhanced after implementation of the three years post-management,which has reached the desired goal.The strategies of the follow-up management suits Guizhou province and widespread application is suggested.

Objective: To analyze the CYP2C19 gene polymorphism in patients with upper digestive system diseases in Anhui Province, so as to provide evidence for individual treatment. Methods: The 307 patients with upper digestive system diseases in the Department of Gastroenterology, The 901st Hospital of Combined Service Force of People＇s Liberation Army were selected. The CYP2C19 genotypes were detected by DNA microarray microarray. The CYP2C19 genotypes and metabolic types in different genders, ages and diseases were analyzed. Results: There were 197 males ( 64.17% ) and 110 females ( 35.83% ) , with the age of ( 58.00±16.13 ) years old. The gene frequency of CYP2C19*1, CYP2C19*2 and CYP2C19*3 was 62.70%, 32.25% and 5.05%, respectively. There were 119 cases (38.76%) of *1/*1 ( 636GG, 681GG ), 129 cases ( 42.02% ) of *1/*2 ( 636GG, 681GA ) , 18 cases (5.86%) of *1/*3 ( 636GA, 681GG ) , 29 cases ( 9.45% ) of *2/*2 ( 636GG, 681AA ) , 11 cases ( 3.58% ) of *2/*3 ( 636GA, 681GA ) , and 1 cases ( 0.33% ) of *3/*3 ( 636AA, 681GG ). In terms of metabolisms, there were 119 cases ( 38.76% ) of fast metabolism type, 147 cases (47.88%) of intermediate metabolism type and 41 cases (13.35%) of slow metabolism type. There were no significant differences in CYP2C19 genotypes and metabolic types among the patients with different gender, age and digestive system diseases ( P＞0.05 ). Conclusion The CYP2C19 genotypes of patients with upper digestive system diseases were polymorphic, mainly the fast metabolism type and the intermediate metabolism type, which could provide reference for the clinical medication of individualized treatment of proton pump inhibitors.

Animals ; Animals, Newborn ; Brain ; drug effects ; metabolism ; pathology ; Disease Models, Animal ; Excitatory Amino Acid Antagonists ; pharmacology ; therapeutic use ; Female ; Hypoxia-Ischemia, Brain ; drug therapy ; metabolism ; Ketamine ; pharmacology ; therapeutic use ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Treatment Outcome

OBJECTIVETo explore the mechanisms involved in the ligustrazine alleviation of the pulmonary artery hypertension (PAH) in patients of chronic obstructive pulmonary disease (COPD) associated with chronic cor pulmonale (CCP) during exacerbation.

METHODSSeventy patients of COPD and CCP with acute exacerbation were randomly and equally divided into control group and treatment group. The control group received standard treatment with antibiotics, antiasthmatic and expectorant medications, and oxygenation; and the ligustrazine treatment group received ligustrazine treatment (80 mg/d; i.v.; for 2 weeks) in addition to the standard treatment. Before and at the end of 2 week treatment, the clinic responses of the two regimens were evaluated, plasma levels of endothelin-1 (ET-1) and nitric oxide (NO) were determined; arterial oxygen partial pressure (PaO2, mean pulmonary arterial pressure (mPAP), outflow tract of right ventricle (RVOT), and internal diameter of right ventricle (RV) were measured.

RESULTSGood clinic benefits were achieved in both the standard and ligustrazine regimens, plasma level of ET-1, values of mPAP, RV and RVOT decreased significantly, plasma level of NO and PaO2 values decreased (all P < 0.01 vs pre-treatment to all parameters). Compared with the control group, ligustrazine greatly enhanced the clinic efficacy from 77.1% to 97.1% (P < 0.05), and also resulted in more significant changes of all these parameters (P < 0.01 vs control group for all parameters). For both groups, the levels of plasma ET-1 were positively correlated with values of mPAP, RVOT, and RV (r = 0.710, 0.853, and 0.766, respectively, all P = 0.000), and negatively correlated with plasma NO and PaO2 (r = - 0.823, and - 0.752, respectively, all P = 0.000).

CONCLUSIONLigustrazine is effective in treating pulmonary artery hypertension during acute exacerbation of COPD and CCP in patients from the plateau area. The observed changes in the plasma levels of NO and ET-1 in response to ligustrazine treatment suggest that ligustrazine may act through the selective effect on pulmonary blood vessels to enhance the synthesis and release of NO and suppress those of ET-1 from lung vascular endothelial cells, thus reducing pulmonary artery pressure and decreasing pulmonary arterial hypertension.

Altitude ; Blood Gas Analysis ; Chronic Disease ; Endothelin-1 ; blood ; Humans ; Hypertension, Pulmonary ; drug therapy ; Nitric Oxide ; blood ; Pulmonary Artery ; physiopathology ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; Pyrazines ; therapeutic use ; Respiration