Abdominal Pain ; etiology ; Child ; Female ; Humans ; Ovarian Cysts ; complications ; Torsion Abnormality

BACKGROUNDHypoxia-inducible factor-1alpha (HIF-1alpha) is one of the pivotal mediators in the response of lungs to decreased oxygen availability, and increasingly has been implicated in the pathogenesis of pulmonary hypertension. Vascular endothelial growth factor (VEGF), a downstream target gene of HIF-1alpha, plays an important role in the pathogenesis of hypoxic pulmonary hypertension and hypoxic pulmonary artery remodelling. In this study, we investigated the dynamic expression of HIF-1alpha and VEGF in pulmonary artery of rats with hypoxia-induced pulmonary hypertension.

METHODSForty male Wistar rats were exposed to hypoxia for 0, 3, 7, 14 or 21 days. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were estimated. Lungs were inflated and fixed for in situ hybridisation and immunohistochemistry.

RESULTSmPAP values were significantly higher than the control values after 7days of hypoxia [(18.4 +/- 0.4) mmHg, P < 0.05]. RVHI developed significantly after 14 days of hypoxia. Expression of HIF-1alpha protein increased in pulmonary arterial tunica intima of all hypoxic rats. In pulmonary arterial tunica media, HIF-1alpha protein was markedly increased by day 3 (0.20 +/- 0.02, P < 0.05), reached the peak by day 7, then declined after day 14 of hypoxia. HIF-1alpha mRNA increased significantly after day 14 of hypoxia (0.20 +/- 0.02, P < 0.05). VEGF protein began to increase markedly after day 7 of hypoxia, reaching its peak around day 14 of hypoxia (0.15 +/- 0.02, P < 0.05). VEGF mRNA began to increase after day 7 of hypoxia, then remained more or less stable from day 7 onwards. VEGF mRNA is located mainly in tunica intima and tunica media, whereas VEGF protein is located predominantly in tunica intima. Linear analysis showed that HIF-1alpha mRNA, VEGF and mPAP were correlated with hypoxic pulmonary artery remodelling. HIF-1alpha mRNA was positively correlated with VEGF mRNA and protein (P < 0.01).

CONCLUSIONHIF-1alpha and VEGF are both involved in the pathogenesis of hypoxia-induced pulmonary hypertension in rats.

Animals ; Blood Pressure ; Chronic Disease ; Hypertension, Pulmonary ; etiology ; Hypertrophy, Right Ventricular ; etiology ; Hypoxia ; complications ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; Male ; Pulmonary Artery ; metabolism ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Transcription Factors ; genetics ; physiology ; Vascular Endothelial Growth Factor A ; genetics ; physiology

Objective To investigated to implement condition of preventive measure and control effect for endemic fluorosis in Fengshun County from 2005 to 2006.Methods It was investigated according to the National Surveillance Program of Endemic Fluorosis.Hupo,Daizai and Anquan Villages of Tangxi Town in Fengshun County were selected as monitoring spots.The usage of reforming water facilities,fluoride content in drinking water and urine of children aged 8-12 years and the prevalence rate of dental fluorosis of children were investigated.Resul tsin 2005 and 2006.a total of 18 reforming water facilities were surveyed and six of which were damaged or out of service.In 2005,the fluoride content in drinking water in the 3 villages was 2.10,1.22 and 0.15 mg/L The prevalence rate of dental fluorosis of children aged 8-12 years was 54.23%(64/118),38.91%(79/203) and 9.10%(6/66).The urine fluoride content of children was 0.95,0.90 and 1.05 mg/L,respectively.In 2006,the fluoride content in drinking water in Hupo,Daizai and Anquan Village was 2.01,1.57 and 0.21 mg/L.The prevalence rate of dental fluorosis of children aged 8-12 years was 26.47%(27/102),12.50%(23/184)and 6.15%(4/65),respectively.The urine fluoride content of children was 0.97,0.61 and 0.59 mg/L.Conclusions The outcome of surveillance data in Fengshun County has reached the sanle level as that of non-disease area.However,the management of reforming water facilities should be improved.

Objective To research the antiviral activity of artesunate (ART) in vitro fighting against both standard laboratory strains and ganciclovir(GCV)-resistance strains of human cytomegalovims(HCMV) and to explore whether fractionation dosage method can obviously enhance the antiviral effect of ART.Methods 1.Cytotoxicity assay to ART was performed by the use of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetry.The 0％ toxic concentration (TC0) were determined,and median cytotoxic concentration (TC50) was calculated with Probit regression method.2.Antiviral activity assays of ART against HCMV:human embryonic lung fibroblast cells (HELs) were infected with standard laboratory strains and GCV-resistance strains of HCMV,respectively,after which virus was removed and overlays of dulbecco's modified eagle medium(MEM) containing different antiviral drugs were added to the wells.All cells were cultured continuously at 37 ℃ in a 50 mL/L CO2 humidified atmosphere for 7-10 days and the cytopathic effect (CPE) was observed under a microscope.When the degree of CPE was clear (+ + +-+ + + +),the values of absorbency at 490 nm of all cell wells were measured by MTT colorimetry.The cell survival rate (CSR)and drug inhibitory rate (IR) for HCMV were calculated.By Probit regression method,the median inhibitory concentration (IC50) of 2 drugs was calculated respectively.3.To explore whether fractionation dosage method could obviously enhance the antiviral effect of ART against HCMV,the experiment was divided into 3 groups and compared with GCV group,respectively:Group 1:ART antiviral compounds were added to cell layers by one dosage.Group 2:Total drug dosage was divided into 3 parts,and each part was added to cell layers once a day for 3 days.Group 3:Total antiviral compounds were divided into 6 and delivery 2 times a day.The values of absorbency at 490 nm of all cell wells were measured by MTT colorimetry.The CSR and viral inhibitory rates were calculated.All data were statistically analyzed by One-Way ANOVA analyzing using SPSS 18.0 statistical software.P value of ＜0.05 was considered to indicate statistical significance.Results 1.Cytotoxicity assay showed that cytotoxicity was not found in the relevant range of ART concentrations under 62.5 μmol/L.TC0 and TC50 value of ART were 62.5 μmol/L and 171.7 μmol/L.2.In concentration of 5 μmol/L,15 μmol/L and 30 μmol/L,ART and GCV could obviously inhibit growth of HCMV AD169 strains.There was no significant difference between them.The value of GCV IC50 was 3.49μmol/L,and the value of ART IC50 was 2.17 μmol/L.Treatment index (TI) of ART was 28.8,and GCV was 716.3.ART could still obviously inhibit growth of HCMV resistant strains,but GCV couldn't.Differences between them were statistically significant.The value of GCV IC50 to HCMV resistant strains was 44.4 μmol/L,and the value of ART IC50 was 2.5 μmol/L.3.Fractionation dosage method (2 times a day) of ART could improve the inhibition rate of virus significantly compared to that used once a day and single dose method.Difference was statistically significant(P ＜ 0.01).GCV delivered as the same method had little different changes in virus suppression ratio(P ＞ 0.05).Conclusions 1.Cytotoxicity was not found in the relevant range of ART concentrations under 62.5 μmol/L.2.ART could obviously inhibit growth of HCMV resistant strains and standard laboratory strains.3.Fractionation dosage method (2 times a day) of ART could improve the inhibition rate of virus significantly compared to that used once a day and single dose method.4.Because the action mode of ART is different from other anti-HCMV drugs,and ART has a high biological activity and fewer side effects,it is expected to become a kind of new antiviral drugs for HCMV infections.

Adolescent ; Adult ; Anemia, Aplastic ; etiology ; therapy ; Benzene ; poisoning ; Bone Marrow Cells ; drug effects ; pathology ; Female ; Humans ; Male ; Occupational Diseases ; etiology ; therapy ; Occupational Exposure ; adverse effects

The chemical investigation on Ganoderma philippii led to the isolation of sixteen compounds by silica gel and Sephadex LH-20 column chromatography. On the basis of spectroscopic data analyses, their structures were elucidated as 2, 5-dihydroxyacetophenone (1), methyl gentisate (2), (S) -dimethyl malate (3), muurola-4, 10 (14) -dien-11beta-ol (4), dihydroepicubenol (5), 5-hydroxymethylfuran carboxaldehyde (6), ergosta-7, 22E-dien-3beta-ol (7), ergosta-7, 22E-dien-3-one (8), ergosta-7, 22E-diene-2beta, 3alpha, 9alpha-triol (9), 6/beta-methoxyergo-sta-7, 22E-dien-3beta, 5alpha-diol (10), ergosta-4, 6, 8(14), 22E-tetraen-3-one (11), ergosta4, 6, 8-(14), 22E-etetraen-3beta-ol (12), 5alpha, 8alpha-epidioxy-ergosta-6, 22E-dien-3beta-ol (13), 7alpha-methoxy-5alpha, 6alpha-epoxyergosta-8-(14), 22E-dien-3beta-ol (14), ergosta-8, 22E-diene-3beta, 5alpha, 6beta, 7alpha-tetraol (15), and ergosta-5, 23-dien-3beta-ol, acetate (16). All the compounds were obtained from this fungus for the first time, and compounds 4 and 5 were isolated from the Ganoderma genus for the first time.
Ganoderma ; chemistry ; Medicine, Chinese Traditional ; Organic Chemicals ; analysis ; isolation & purification

Shiwei Dangguiyin(SWDGY)is mainly composed of Radix Angelicae Sinensis,Radix Adenophorae,Radix Notogenseng,Radix Bupleuri,etc. Oral administration of SWDGY could significantly inhibit the metatarsal swell- ing eaused by dimethylbenzene in rats,raise the pain threshold in hot-plate test and depress the torsive reaction caused by acetic acid in mice.In vitro SWDGY exerted bacteriostatic and bacteriocidal effects on Staphylococcus aureus,Bacil- lus pyocyaneus,Escherichia coli,Streptococcus A,B and C.It was shown that SWDGY possessed anti-inflammatory,analgesic and antiseptic effects in vitro.In mice LD_(50) of SWDGY by oral administration was more than 840g/kg.Affer cral adminstration in a daily dose of 189.Sg/kg continuously for one month in rats, no toxic reactions appeared,This dosage was 118.6 times as much as the clinical one.

Objective To explore the application of nanodisc in functional and drug discovery research of G protein-coupled receptor (GPCR).Methods The purified recombinant 5-Hydroxytryptamine 2B receptor (5-HT2BR) was reconstituted into nanodisc complex.Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and size exclution chromatography were performed to evaluate the reconstitution reaction,followed by the use of surface plasmon resonance to validate the ligand-binding activity of 5-HT2BR after reconstitution.Results 5-HT2B R was effectively self-assembled into nanodisc while maintained its binding activity toward the antagonist SB204741.Conclusions The presented study provided potential application of 5-HT2B R-nanodisc for the development of subtype-selective drugs against 5-HT2B R and the fundamental of utilizing nanodisc for GPCR structural and functional studies as well as drug discovery.

Objective To analyze GJB2 235delC monoallelic mutation carrier individuals and test the possible presence and incidence of audiometric abnormalities among 30 - 60 years old carriers of the 235delC mutations.Methods A total of 32 unrelated subjects with nonsyndromic hearing loss were screened for the 235delC mutation.Tonal audiometric analysis was performed on the 235delC mutation carrier group and on a non-carrier control group.Results Audiometric evaluations in the control group showed the presence of thresholds within normal limits at all frequencies,while carriers of the 235delC mutation presented with decreasd hearing at 1000 Hz and 2000 Hz (age 40-49 years and 50-59 years) ,and 4000 and 8000 Hz( age 30-59 years) ,P ＜ 0.05.The hearing loss of carriers gradually increased with age.Conclusions GJB2 235delC heterozygous carriers may be a risk group for high-frequency hearing loss.Hearing thresholds may deteriorate in the intermediate frequencies over the age of 40.

Based on the chemical structures of magnolol and honokiol,a series of small molecular derivatives were designed for the treatment of Alzheimer's disease.Through the Discovery Studio,five compounds (6a-6e) exhibited the inhibitory activity against Aβ and Tau proteins in all of the designed compounds.Then the five compounds are chemically synthesized and their biological activities were tested by thioflavin T.The result showed that compound 6a had inhibitory effect on the aggregation of two kinds of target proteins at the concentration of 100 μmol/L,which deserves further research.