Objective To examine the changes of the airway resistance(AR) in asthmatic bronchitis children before and after budeso-nide-solution inhaled therapy.Methods Fifty-six cases of asthmatic bronchitis children were randomly divided into A(regular treatment+budesonide-solution inhaled) and B groups(regular treatment),and 30 normal children at the same age as control group.The AR was eva-luated by Microloop lung function meter with MicoroRint sensor.The changes of AR were compared within above 3 groups.Results AR in asthmatic bronchitis children increased significantly compared with normal children.After 2 weeks treatment,AR decreased significantly in both A and B groups compared with that of 2 groups before therapy,AR in A groups declined to normal control level,but still kept higher level in B groups.Conclusions AR in asthmatic bronchitis children increase significantly.The effect of Budesonide-solution in asthmatic bronchitis children is partly via reducing AR to improve ventilated condition.

OBJECTIVE: To discuss the key considerations and evaluation criteria in designing a clinical comparison study to assess the clinical similarity of biosimilars. METHOD: Relevant guidelines and literatures on clinical similarity evaluation were reviewed, the cases were analyzed, discussions were carried out with biotech industry sponsors and clinical and statistical experts, the key considerations and evaluation criteria were proposed for assessing the clinical similarity of biosimilars. RESULTS AND CONCLUSION: The clinical similarity criteria should reflect the characteristics of the biological products. It is critical to select right patient population, clinical endpoints and equivalence/non-inferiority margin for development of different biosimilar products on the basis of fully understanding the quality, efficacy and safety profile of the original biological products. To set up the clinical similarity criterion and selection of the equivalence/non-inferiority margin, the consistency of the therapeutic effect of the reference product and subject variability need to be taken into consideration for robust evaluation of clinical similarity.

Animals ; Arecoline ; pharmacology ; Cholinergic Agonists ; pharmacology ; Female ; Guinea Pigs ; In Vitro Techniques ; Male ; Muscle Contraction ; drug effects ; Muscle, Smooth ; physiology ; Pyloric Antrum ; physiology ; Receptor, Muscarinic M3 ; metabolism

OBJECTIVETo explore the effect of Bushen Huoxue Compound (BHC) on lactate dehydrogenase (LDH) leakage, expressions of vascular endothelial growth factor (VEGF) and VEGF mRNA in retinal Muller cells under high glucose condition or advanced glycosylation end products (AGEs) condition by using serum pharmacological method.

METHODSThe retinal Müller cells of 5-7 days post-natal Sprague Dawley (SD) rats were cultured with modified enzyme-digestion method. Purified retinal Muller cells were cultured in normal conditions, high glucose condition (50 mmol/L) or AGEs (50 mg/L and 100 mg/L) conditions, and BHC-containing serum was added to culture medium. The LDH leakage and VEGF expressions were measured by enzyme-linked immunosorbent assay (ELISA). In addition, the relative expression of VEGF mRNA was tested by reverse transcription polymerase chain reaction (RT-PCR).

RESULTSCompared with the normal control group, expressions of VEGF and VEGF mRNA were significantly increased in the high glucose group, the low dose AGEs group and the high dose AGEs group (all P < 0.01). The LDH leakage was obviously increased in the high dose AGEs group, when compared with the normal control group and the high glucose group (P < 0.01). The LDH leakage, expressions of VEGF and VEGF mRNA were obviously decreased by BHC-containing serum both in high glucose and AGEs conditions (P < 0.05, P < 0.01). BHC-containing serum had no significant effect on the LDH leakage and expressions of VEGF and VEGF mRNA in normal conditions (P > 0.05).

CONCLUSIONSAGEs intervention could obviously lower the stability of Müller cell membrane. Up-regulated expressions of VEGF and VEGF mRNA in cultured Müller cells could be induced by AGEs or high glucose. BHC-containing serum could stabilize the stability of Müller cell membrane, inhibit the transcription of VEGF mRNA and decrease the protein expression of VEGF, which might be one of important mechanisms for preventing and treating diabetic retinopathy.

Animals ; Cells, Cultured ; Diabetic Retinopathy ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Ependymoglial Cells ; Glucose ; L-Lactate Dehydrogenase ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A

Adult ; Chronic Disease ; Female ; Humans ; Placenta ; pathology ; Placenta Diseases ; diagnosis ; pathology ; Pregnancy

Objective To investigate the pathologic mechanism of radiofrequency ablation ( RFA ) combined with intravenous infusion of thermosensitive liposome encapsulated vinorelbine (TL-Vin) in treating liver tumors, and to analyze the effect of combination therapy on the long-term survival rate. Methods H22 liver adenocarcinoma tissue was subcutaneously implanted into ICR mice to establish the animal models. At the first experimental period, 40 mice were randomly and equally divided into 5 groups to receive different therapeutic scheme (using different TL-Vin concentrations). Twenty-four hours after the treatment the tumor specimens were collected, the necrotic areas were measured separately, and the optimal TL-Vin concentration was determined. At the second experimental period, 13 mice were randomly selected to receive treatment. Half an hour after the treatment the tumor tissues were collected and the TL-Vin concentration within the tumor was determined. At the third experimental period, 32 mice were randomly and equally divided into 4 groups, and 90 days after treatment the tumor growth curve was drawn. The survival rate was compared between each other of the groups. Results Compared with pure RFA group, TL-Vin + RFA significantly increased tumor coagulation extent (P<0.01). But free-VIN+RFA had similar tumor necrotic extent as that produced by RFA alone (P>0.05). Tumor coagulation area in TL-Vin + RFA group was bigger than that in free-VIN + RFA group at the concentration of 10 mg/kg [(341.8 ± 65.4)mm2 vs (225.3 ± 25.4)mm2, P < 0.01]. In TL-Vin group the coagulation margin was clear. The mean intratumoral Vinorelbine accumulation in TL-Vin + RFA group was 10 folds of that in free-Vin group [(1 156.5 ± 158.3)ng/ml vs (194.5 ± 52.3)ng/ml, P = 0.005]. TL-Vin +RFA had better survival result than that of RFA alone (37.6 ± 20.1 days vs. 23.4 ± 5.0 days, P=0.015), as well as than that of free-Vin + RFA [(37.6 ± 20.1)days vs (23.3 ± 1.2)days, P = 0.016]. Conclusion Thermosensitive liposomal chemotherapies (Vinorelbine) can be selectively delivered at the edge of RFA coagulation area and thus effectively increase RFA-induced tumor coagulation and prolong the end-point survival in experimental mice.

Objective:To explore the expressions of miRNAs related to accelerating senescence in serum of the patients with amnestic mild cognitive impairment (aMCI), and to clarify their effects in the pathogenesis of aMIC.Methods:The levels of miRNAs related to accelerating senescence (miR-132, miR-193b, miR-130b, miR-20a, miR-296, miR-329 and miR-206) were measured in the serum of the patients with aMCI (aMCI group,n=66) and healthy controls(control group,n=76) using quantitative real-time PCR(qRT-PCR).The genes targeted by the altered miRNAs were predicted by TargetScan 6.0.DAVID was used to analyze the function of miRNA target genes.The serum levels of brain derived neurotrophic factor (BDNF) and silent in formation regulator 1(SIRT1) were measured by enzyme-linked immunosorbent assay (ELISA) method.Results:The expression levels of miR-206 and miR-132 in serum of the patients in aMCI group were significantly higher than those in control group (P<0.05).BDNF and SIRT1 were both target genes of miR-206 and miR-132.The levels of BDNF (29.50 μg·L-1± 3.13 μg·L-1) and SIRT1 (1.86 μg·L-1± 0.25 μg·L-1) in serum of the patients in aMCI group were both obviously lower than those in control group (BDNF: 32.29 μg·L-1±3.66 μg·L-1;SIRT1: 2.10 μg·L-1± 0.29 μg·L-1, P<0.05).Conclusion:The expression levels of miR-206 and miR-132 in serum of the aMCI patients are significantly up-regulated.Both of them might be involved in the pathogenesis of aMCI through inhibiting the BDNF and SIRT1 expressions.

Objective To evaluate the feasibility of reconstructing horizontal periodontal bone defects by tissue engineering based on bone marrow stromal cells(BMSCs)as seed cells and enamel matrix proteins(EMPs)as growth factors. Methods Two healthy rhesus monkeys were selected, and BMSCs were isolated from iliac marrow and serial subcultivation was conducted. The cells of induced BMSCs at passage 3 were harvested and mixed with Bio-oss collagen. The models of horizontal periodontal bone defects were established surgically in each buccal side of the posterior teeth, and were divided into four groups (blank control group, material group, cells/material group and cells/material/EMPs group). The histological and Micro-CT observation were carried out 8 weeks later. Results In the blank control group, the defects were filled with fibrous connective tissue. There was newly-formed alveolar bone in the material group. In the cells/material group, periodontal regeneration could be observed, while the newly-formed cementum was irregular and less in quantity. In the cells/material/EMPs group, the amount of newly-formed alveolar bone was larger, and the newly-formed cementum was continuous and regular. Conclusion The tissue engineering technique of BMSCs as seed cells in combination with EMPs induction can significantly promote the regeneration of periodontal tissue.

OBJECTIVETo explore the in vitro anti-platelet effects of Ginsenoside -2A,a purified extract from Panax notoginseng.

METHODSPlatelet rich plasma (PRP) was prepared routinely from venous blood samples of patients with essential hypertension and normal persons. PRP was incubated with different concentrations of Nifedipine, Ginsenoside-2A ,and SK&F96365. Maximal platelet aggregation rate[ PAG (M) ] induced by 2 micromol/L ADP was taken as the observed index. Five-minute PAG( M) was determined for 5 consecutive times.

RESULTS(1) PAG (M) in essential hypertension group was 0. 89 +/- 0. 06, which was higher than that in the normal group (0. 68 +/-0. 07 ) with significant difference (P <0.01). (2)Nifedipine of two concentrations (10 p.mol/L,20 pVmol/L) had no effect on PAG(M) in either essential hypertension group or normal group(P >0. 05). (3)Different concentrations of SK&F96365 (2.5 micromol/L,5 micromol/L,10 micromol/L and 20 micromol/L) could inhibit the PAG(M) in essential hypertension group; (4) Differen concentrations of Ginsenoside -2A (2. 5 micromol/L, 5 micromol/L, 10 micromol/L and 20 micromol/L) could inhibit PAG ( M) in essential hypertension group; three concentrations of Ginsenoside -2A (5 micromol/L, 10 micromol/L, 20 micromol/L) could inhibit the PAG(M) in the normal group (all P <0.05).

CONCLUSIONPlatelet aggregating function in essential hypertension patients was obviously higher than that in the normal persons and platelets was in the high reactive status. Nifedipine had no inhibitive effect on platelet aggregation. SK&F96365 could inhibit the platelet aggregation. Ginsenoside-2A could inhibit platelet aggregation, and had the definite anti-platelet action.

Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Ginsenosides ; administration & dosage ; pharmacology ; Humans ; Imidazoles ; administration & dosage ; pharmacology ; Nifedipine ; administration & dosage ; pharmacology ; Platelet Aggregation Inhibitors ; administration & dosage ; pharmacology

OBJECTIVETo explore the effect of Gecko Swinhonis Gunther freeze-dried powder (GFP) in inducing apoptosis of C6 glioma cells.

METHODSThirty mice were randomly divided into three groups and treated with intraperitoneally injection of cisplatin, orally taken GFP or distilled water respectively. After treatment for 20 days, the serum of mice was collected for treating the C6 glioma cells. The apoptosis state of cells was observed by morphological examination, flow cytometry and TUNEL method, and the cell apoptosis related gene expression of bcl-2 and bax were determined by S-P immunocytochemical assay.

RESULTSThe C6 glioma cell apoptosis induction of GFP contained serum in vitro could be confirmed by morphological examination, flow cytometry analysis and TUNEL method. Comparison between the GFP treated group and the blank control group on intracellular bcl-2 gene expression showed no difference, but bax gene expression was higher in the GFP treated group.

CONCLUSIONGFP contained serum could induce C6 glioma cell apoptosis, its mechanism might be related with the up-regulation of bax gene.

Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Glioma ; chemistry ; genetics ; pathology ; Humans ; Male ; Materia Medica ; pharmacology ; Mice ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; genetics ; Random Allocation ; Serum ; Tumor Cells, Cultured ; bcl-2-Associated X Protein