Objective: To search for new isoflavones with more potent antitumor activities from the target compounds synthesized by inserting a double bond or an acetylene bond between chromone and its 3-substituted phenyl, ester and hydroxymethyl groups, or by formation of an amide of 3′ or 4′-amino group of isoflavones with norcantharidin. Methods: The key intermediate 3-iodo-7-methoxyl-4H-chromen-4-one (5) was prepared with 2-hydroxyl-4-methoxyl- acetophenone and ethyl formate. The target compounds with 3-substituted double bond or acetylene groups were synthesized by Heck coupling and Sonogashira coupling reaction; the amide compounds were synthesized by Suzuki coupling reaction and amide formation of 3′ or 4′-amino group of isoflavones with norcantharidin. All of the target compounds were confirmed by 1HNMR, MS and IR spectra. The IC50 values of target compounds were determined by the standard method using two kinds of human tumor cell lines, colon cancer cell line HCT116 and liver cancer cell line SMMC 7721 to study their anti-tumor activities. Results: All the 17 target compounds obtained had certain anti-tumor effect in vitro, with compounds 7h and 7e showing better anti-tumor effects, which were similar to that of control curcumin and more potent than that of genistein in vitro. Conclusion: The insertion of a double bond or an acetylene bond between chromone and its 3-substituted phenyl, ester and hydroxymethyl groups may promote the anti-tumor activities of isoflavone analogues. It seems that the formation of an amide of 3′- or 4′-amino group of isoflavones with norcantharidin has no noticeable promotion effect on the anti-tumor activities.

Objective To study the cell vitality and ultra-structure of in vitro cultured fetus chondrocytes exposed to different doses of fluoride.Methods Primary chondrocytes were obtained from articular cartilage of the 24-27 weeks,aborted and dead fetuses.The third generation of primary cultured chondmcytes were exposed to concentrations of 0,10-2,5 × 10-3,10-3,10-4,10-5,10-6,10-7 and 10-8 mol/L fluoride for 24,48 and 72 h.Cell vitality was detected with Cell Counting Kit-8 (CCK-8) and ultra-structure of chondrocytes was observed by transmission electron microscope.Results The cell vitalities of chondrocytes exposed to doses of fluoride (10-2,5 ×10-3,10-3,10-4,10-5,10-6,10-7 and 10-8 moL/L) for 24,48 and 72 h were(15.04 ± 0.55)％,(62.53 ± 1.03)％,(100.34 ± 5.19)％,(111.40 ± 3.69)％,(121.47 + 6.09)％,(129.95 ± 4.96)％,(121.81 ± 4.97)％,(111.00 ± 1.63)％;(10.35 ± 0.64)％,(35.23 ± 2.41)％,(110.30 ± 2.07)％,(113.66 ± 6.98)％,(120.36 ± 6.23)％,(133.40 ± 5.80)％,(126.06 ± 5.40)％,(115.62 ± 7.33)％; (6.19 ± 0.16)％,(18.44 ± 0.21)％,(120.83 ± 4.93)％,(123.77 ± 4.82)％,(129.09 ± 5.21)％,(140.44 + 4.18)％,(131.99 ± 7.00)％,(124.10 ± 3.68)％,respectively.The cell vitalities of 10-2,5 × 10-3 mol/L fluoride groups were significantly lower than that of the control group (all P ＜ 0.05).The cell vitality of 10-2 mol/L group was significantly lower than that of the 5 × 10-3 mol/L group (P ＜ 0.05).Doses of fluoride (10-2,5 × 10-3 mol/L) could inhibit the cell vitality and promote the apoptosis of chondrocytes in vitro with increasing doses and prolonged time.The cell vitalities of 10-3,10-4,10-5,10-6,10-7,10-8 mol/L of fluoride groups were significantly higher than that of the control group (except the 24 h 10-3 mol/L,P ＜ 0.05).Between 10-4 and 10-3 mol/L groups(the vitalities of 48 h and 72 h were higher,but not significantly); 10-5 and 10-4 mol/L groups (the vitality of 72 h was higher,but not significantly); 10-6 and 10-5 mol/L groups,the cell vitalities were significantly higher than that of the control group(all P ＜ 0.05).Between 10-7 and 10-6 mol/L groups,10-8 and 10-7 mol/L groups (the vitality of 72 h was lower,but not significantly),the cell vitalities were significantly lower than that of the control group(all P ＜ 0.05).Doses of fluoride(10-3-10-8 mol/L) could promote the cell vitality of chondrocytes in vitro with prolonged time.The optimal concentration for the promotion was 10-6 mol/L.The cells of the control group were characterized as regular morphology,the abnormal surface microvillis,abundant cytoplasm and mitochondrial,abundant and slightly expanded rough endoplasmic reticulums and low electron-dense materials.The cells of 10-6 mol/L fluoride group had the following changes,increased and swell mitochondrial,hypertrophy and expanded rough endoplasmic reticulums.The cells of 5 × 10-3 mol/L fluoride group had the following changes,decreased microvillis,invaginated cell membrane,pyknosis and apoptotic body.Conclusion Doses of fluoride (10-3-10-8 mol/L) can promote the proliferation of human chondrocytes cultured in vitro.Doses of fluoride (10-2,5 × 10-3 mol/L) can promote the apoptosis of human chondrocytes cultured in vitro.

The complex level of constructing biopharmaceutics classification system of Chinese materia medica CMMBCS) was the study of traditional Chinese compound, on the premise of insisting that the multicomponent simultaneous determination, when carrying out the study of intestinal permeability, the primary task was to define the source of the components that was absorbed through the intestinal wall, namely, which medicinal material the components belonged to in traditional Chinese compound. The technology of chemical fingerprint and in vitro everted gut sac model were used in this research to make multicomponent an intuitive source attribution which permeated the intestine in the classic formula Gegen Qinlian decoction, and to lay the foundation for the further qualitative and quantitative research of intestinal permeability.
Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; pharmacokinetics ; Intestines ; metabolism ; Male ; Permeability ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar

Objective To explore the influence of montelukast on plasma nitric oxide in preschool children with asthma.Methods Forty-four preschool children with asthma aged 2-5 years who firstly met a criterion of asthma and treated 4 weeks with montelukast were investigated;and nitric oxide levels of plasma were inspected respectively before treatment and after treatment 1 week,4 weeks.Results The level of nitric oxide in the plasma of asthmatic children was obviously higher than that in normal control group(P

Objective To investigate the effect of growth differentiation factor 11 ( GDF11 ) on aorta in apolipoprotein E-Null( ApoE-/-) mice and its possible mechanisms. Methods Four-week-old healthy male ApoE-/-mice were fed with high-fat diet for 1 week and were then divided into 4 groups:vehicle group(n=10), GDF11 group (n=10),adeno-associated virus-green fluorescent protein group(AAV-GFP group, n=10), and AAV-GDF11 group ( n=10 ) . The mice received intraperitoneal injection with phosphate buffered saline, GDF11 protein, a single injection of purified AAV-GDF11 or AAV-GFP through the tail vein, respectively. After 4 weeks, serum GDF11/8 level and endothelium-dependent vasodilatation were detected. After 12 weeks, serum GDF11/8, interleukin-6 (IL-6), tumor necrosis factor-α( TNF-α), total cholesterol ( TC), triglycerides ( TG), oxidized low density lipoprotein(ox-LDL), and free fatty acids(FFA)levels were measured, the plaque areas in aortic enface and cross sections were measured by oil red O or HE staining, the macrophages/T lymphocytes infiltration in plaques were detected with immunohistochemistry, and the mRNA expressions of IL-6, TNF-α, and IL-10 were determined by real-time PCR. Results Compared with vehicle or AAV-GFP groups, GDF11 and AAV-GDF11 groups presented improved endothelium-dependent vasodilatation, decreased levels of blood inflammatory factors, blood lipid, reduced plaque on face area sections[Vehicle group : GDF11 group:(31. 23 ± 3. 12)% vs (17. 18 ± 2. 17) %;AAV-GFP group : AAV-GDF11 group:(38.01±4.43)% vs(14.54±2.86)%,P<0.05]andcrosssections[Vehiclegroup :GDF11 group:(19. 87 ± 2. 11)% vs (10. 32 ± 1. 47)%;AAV-GFP group : AAV-GDF11 group:(23. 02 ± 2. 76)%vs (9.06±1.63)%, P<0. 05]. There were less macrophages and T lymphocytes infiltration in plaques and lower mRNA expressions of inflammatory factors at aortic wall. Conclusion GDF11 reduces the area of atherosclerotic lesion in ApoE-/-mice, which may be involved in endothelial protection, such as to reduce inflammatory reaction, and to change cellular composition in plaques.

Objective To investigate the effects of growth differentiation factor 11 ( GDF11 ) on β-cell function in db/db mice and its possible mechanism. Methods Twenty eight-week-old male db/db mice were randomizedtoi.p. administration of GDF11(0.3mg·kg-1·day-1)or equivalent PBS(n=10)for 6 weeks.10age-matched male db/m were used as normal control, received equivalent PBS injection for 6 weeks. Blood glucose levels, body weights and food intake were monitored weekly. IPGTT and glucose-stimulated insulin secretion ( GSIS) were analyzed. After 6 weeks of intervention, serum HbA1C , TG, TC, and FFA were measured respectively. The concentrations of hormones in serum and pancreas were evaluated. The mRNA expression of Pdx-1, MafA, Nkx6. 1, and insulin2 were determined by RT-PCR. The expression of phosphorylated Smd2 (P-Smad2), Smad2 in islet were examined by western blot. Results Compared with NC group, GDF11 administration decreased FBG, HbA1C , modified lipid profiles. GDF11 improved glucose tolerance and augmented GSIS. Moreover, GDF11 increased serum insulin and pancreatic insulin content, while decreased serum glucagon concentration. The expression of Pdx-1, MafA, Nkx6. 1, and Insulin2 were significantly increased in GDF11 group. GDF11 elevated the expression of P-Smad2 in islets. Conclusion s GDF11 may preserve β-cell function and facilitate the secretion and production of insulin. Diminishing the metabolic abnormalities, alleviating the secretion of glucagon, as well as maintaining the key transcript factor activation may contribute to the amelioration of β-cell function after GDF11 administration. Smad2 pathway may be related to the protective effects of GDF11.

Objective To investigate the effect of ropiyacaine combined with intra-spinal epidural anesthesia by using the same volume but different injection speed on anaesthetic level.Methods 80 cases of patients of ASA～Ⅱdegree suitable to use intra-spinal epidural combined anesthesia for gynecologic operation were selected and ran- domly divided into three groups,0.75 % ropivacaine 2mg(15mg)administered,group A the speed of injection was 10 seconds,group B injection speed was 20 seconds,group C injection speed was 30 seconds,the anaesthetic level reached T_(10).The time of highest level in spinal anesthesia,30 minutes after spinal anesthesia MAP,and number of cases need to add epidural drug were all recorded.Results The best effect of anesthesia was found in group B,the block level of anesthesia was satisfactory,blood dynamic was stable,and there was no need to add epidural drug.Conclusion The speed of 0.75 % ropivacaine 2ml spinal epidural combined with anesthesia was suitable at the speed of 20 seconds.

Animals ; Chemical and Drug Induced Liver Injury ; drug therapy ; Liver ; drug effects ; pathology ; Mice ; Silymarin ; pharmacology ; Ursodeoxycholic Acid ; pharmacology

OBJECTIVETo discuss the influence of reducing buccolingual width of artificial crown on distribution of biting force and masticatory efficiency in unilateral distal-extension implant denture and provide valuable information for the design of buccolingual width. To find a design that the biting force of implant prothesis was less evident than those on the contralateral natural teeth without compromising masticatory efficiency.

METHODST-Scan II occlusal analyzer and 722 grating spectrophotometer were used to analyze the distribution of biting force and masticatory efficiency in unilateral distal-extension implant denture. Heat-cured resin crowns with three different buccolingual width (group A: standard buccolingual width; group B: the buccolingual width was reduced by 1/4; group C: the buccolingual width was reduced by 1/3) were designed as follow, one was contoured with standard buccolingual width, the other two were made with reducd buccolingual width by 1/4 and 1/3.

RESULTSThe ratio of biting force (ROF) of group C was 16.25%, which was significantly lower than group A (27.38%) and B (22.60%) (P < 0.0083). The X axis displacement of center of occlusal force (COF) of group C was 2.0 mm, which was significantly difference with group A (1.5 mm, P = 0.004). The masticatory efficiency absorbance A value (MEA) of group C was 0.217, which was significantly lower than group A (0.345, P = 0.005) and B (0.289, P = 0.004).

CONCLUSIONSAccording to the study, the buccolingual width of the crown reduced by 1/4 was a more ideal design for unilateral distal-extension implant denture.

Adult ; Aged ; Bite Force ; Crowns ; Dental Occlusion ; Dental Prosthesis Design ; Dental Prosthesis, Implant-Supported ; Female ; Humans ; Male ; Mastication ; Middle Aged ; Spectrophotometry

OBJECTIVETo investigate the efficacy and safety of secreted interferon in treatment of chronic hepatitis B.

METHODSA multi-center randomized open-label controlled clinical trial was carried out. The patients of the study group were treated by secretory human interferon alpha-2a, and the patients of the control group were treated with an ordinary interferon.

RESULTSALT normalization rate in the secreted interferon group was 48.3% and it was higher at the end of treatment than that of the control group, but there was no difference between the two groups at the end of the follow-up. HBV DNA dropped more in the study drug group, but there was no difference in the normalization rate between the two groups. HBeAg seroconversions in secreted interferon group and in the control interferon group were 19.0% and 18.4% respectively. The safety of the two types of interferon was satisfactory.

CONCLUSIONSSecreted interferon was superior to ordinary interferon in ALT normalization and HBV DNA drop at the end of treatment in chronic hepatitis B patients, but there was no difference at the end of the follow-up. There was also no difference in HBeAg negative and HBeAg seroconversion between the two groups.

Adolescent ; Adult ; Antiviral Agents ; adverse effects ; therapeutic use ; DNA, Viral ; blood ; Follow-Up Studies ; Hepatitis B virus ; isolation & purification ; Hepatitis B, Chronic ; therapy ; Humans ; Interferon-alpha ; adverse effects ; therapeutic use ; Middle Aged ; Recombinant Proteins ; Treatment Outcome