AIMTo investigate the preparation of diclofenac sodium pulsatile release pellets (DS-PRP), the release in vitro and the pharmacokinetics of the drug.

METHODSDiclofenac sodium (DS) core pellets prepared by extrusion-spheronization technology were coated in a mini-fluidized bed spray coater with swelling material as the inner coating swelling layer and ethylcellulose aqueous dispersion as the outer coating controlled layer. The effects of formulation and medium on pulsatile release of DS were investigated under release rate test. Pharmacokinetic and bioavailability study in eight human subjects were performed by HPLC method.

RESULTSThe delayed-release time and release rate of DS from DS-PRP were influenced obviously by the swelling material, the concentration of SDS in medium, the coating level of the inner swelling layer and the outer controlled layer. In vitro, the delayed-release time T0.1 was 3.1 h, and the pulsed-release time T0.1-0.2 was 1.2 h. In vivo, the delayed-release time Tlag was 2.8 h, and the bioavailability was (91 +/- 12)%.

CONCLUSIONThe release of drug from DS-PRP was shown to be in pulsed way both in vitro and in vivo.

Adult ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; pharmacokinetics ; Biological Availability ; Cellulose ; analogs & derivatives ; chemistry ; Delayed-Action Preparations ; Diclofenac ; administration & dosage ; pharmacokinetics ; Humans ; Hydrogen-Ion Concentration ; Male ; Random Allocation ; Sodium Dodecyl Sulfate ; chemistry

Objective To determine the effect of local mild hypothermia on patients with acute cerebral infarction and ascertain its optimal therapeutic window. Methods According to the time receiving treatment, 114 patients with acute cerebral infarction were divided into group A (≤6 h), group B (6-24 h) and group C (≥ 24 h). Then, each group was subdivided into 2 groups at random: treatment group (A1, B1, C1) and control group (A2, B2, C2). Patients in the control group were subjected to such conventional therapy as anti-platelet aggregation. Patients in the treatment group were treated with local mild hypothermia (33-35 ℃ body-core temperature) for 48 h besides conventional therapy. Clinical outcomes were assessed by the National institutes of health stroke scale (NIHSS) on admission and 7, 14,30 d after treatment. Furthermore, we detected the serum level of nitrogen monoxidum (NO) and superoxide dismutasc (SOD) on admission, and 7 and 14 d after treatment. Results Compared with the control group, treatment group enjoyed significantly decreased scores of NIHSS 7, 14 and 30 d after treatment and significantly decreased level of NO 7 and 14 d after treatment (P＜0.05), but obviously increased SOD vitality 7 and 14 d after treatment (P＜0.05). No significant differences in terms of NIHSS scores, level of NO and SOD vitality were noted between group C1 and group C2 at each time point (P＞0.05). Group Al and group B1 had obviously lower scores of NIHSS than group C1 on the 7th, 14th and 30th d of treatment, and had significantly lower level of NO and obviously increased SOD vitality as compared with group C1 on the 7th and 14th d of treatment (P＜ 0.05), and group A1 enjoyed its advantage.Conclusion Early local mild hypothermia therapy can improve neurological function in patients with acute cerebral infarction. The mild hypothermia induced within 6 h may be optimal therapeutic window;mild hypothermia induced at 6-24 h is less effective and that above 24 h is non-effective.

To separate and identify the chemical constituents from the leaves of Broussonetia papyrifera (Linn.) Vent, various columns including Diaion HP-20, Toyopearl HW-40C, Sephadex LH-20, silica gel were employed for the isolation and purification of compounds from the leaves of B. papyrifera. The structures of the compounds were elucidated by their physiochemical characteristics and spectral data. Nineteen compounds were isolated from the leaves of B. papyrifera and their structures were identified as apigenin (1), apigenin-7-O-beta-D-glucopyranoside (2), chrysoerid-7-O-beta-D-glucopyranoside (3), apigenin-7-O-beta-D-glucopyranuronide (4), vitexin-7-O-beta-D-glucopyranoside (5), luteolin (6), 5,7,4'-trihydroxyl-6-C-[a-L-rhamnopyranosyl (1-->2)]-beta-D-glucopyranosyl flavone (7), 5,7,4'-trihydroxyl-8-C-[a-L-rhamnopyranosyl (1-->2)]-beta-D-glucopyranosyl flavone (8), saponaretin (9), vitexin (10), benzyl benzoate-2, 6-di-O-beta-D-glucopyranoside (11), (2R, 3R, 5R, 6S, 9R)-3-hydroxy-5,6-epoxy-beta-ionol-2-O-beta-D-glucopyranoside (12), (2R, 3R, 5R, 6S, 9R)-3-hydroxyl-5,6-epoxy-acetyl-beta-ionol-2-O-beta-D-glucopyranoside (13), ficustriol (14), (6S, 9S)-roseoside (15), 3beta-hydroxy-5alpha,6alpha-epoxy-beta-ionone-2alpha-O-beta-D-glucopyranoside (16), icariside B1 (17), sammangaoside A (18), 3-hydroxy-5alpha,6alpha-epoxy-beta-ionone (19). Compounds 11, 12 and 13 are new compounds, the others are isolated from this genus Broussonetia for the first time.
Apigenin ; chemistry ; isolation & purification ; Broussonetia ; chemistry ; Glucosides ; chemistry ; isolation & purification ; Luteolin ; chemistry ; isolation & purification ; Molecular Structure ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry

OBJECTIVETo establish the 3T3 mouse fibroblast neutral red uptake (NRU-PT) phototoxicity test method, and evaluate the practicality of the method in detecting potential phototoxicity of the cosmetic products.

METHODSFifteen phototoxic and 9 non-phototoxic chemicals were tested in our laboratories, the phototoxic potential of the test chemicals was evaluated in a prediction model in which either the photo irritation factor (PIF) or the mean photo effect (MPE) was compared with the coherence and sensitivity of the method. 20 kinds of functional cosmetics were detected and the results were analyzed by the 3T3 NRU-PT in vitro and Guinea pig skin phototoxicity test (in vivo).

RESULTSBoth PIF and MPE of the chemicals were highly reproduced, and the correlation between in vitro and in vivo data was almost perfect. All the non-phototoxic provided a negative result, while 14 of the 15 phototoxic tested chemicals gave clear positive results. For cosmetics, the correlation between in vitro and in vivo data was consistent.

CONCLUSIONThe 3T3 NRU PT test was established successfully, it should be used as a good alternative method for assessing the phototoxic potential of the chemicals and cosmetics in China.

3T3 Cells ; drug effects ; Animals ; Animals, Newborn ; Cosmetics ; toxicity ; Dermatitis, Phototoxic ; Fibroblasts ; drug effects ; Guinea Pigs ; Mice ; Toxicity Tests

OBJECTIVETo evaluate the quality and clinical applicability of pyrosequencing assay kit for detecting hepatitis B virus resistance (HBV DRT).

METHODSSerial dilutions of the International Standard for HBV DNA were used to test the detection limit of the PCR for HBV DRT. Plasmids containing the either a wild-type (WT) copy or one of 10 mutant (MT) copies of the HBV RT gene were used to prepare a series of samples with various mutation ratios. To construct the linear relationship between the true mutation rate and the detected mutation rate, each sample was repeated at least 10 times. A total of 102 clinical samples were analyzed by Sanger sequencing and retested by the PCR for HBV DRT to determine the concordance of these two methods.

RESULTSThe lower detection limit of the PCR for HBV DRT was 50 IU/ml. Except for the RT236 MT, the correlation between the true mutation rate and the detected mutation rate for the other nine resistance-related mutation sites were excellent, with R² more than 0.98 (P less than 0.001). Among the 102 clinical samples, four were not amplified successfully by PCR. The results were significantly different between the PCR for HBV DRT method and the Sanger sequencing method (x² = 71.2, P less than 0.001), and concordance was observed for 897/969 (92.6%) amino acid positions in 98 samples. Concordant results were achieved in 46/98 (46.9%) samples at all 10 mutation sites. For detection of a single mutation site, concordance rates ranged from 71.5% to 100% at the 10 mutation sites, respectively. Analysis of discordant samples showed that in 87.5% (63/72), Sanger sequencing detected WT and the PCR for HBV DRT detected WT/MT. In 5.6% (4/72) of samples, Sanger sequencing detected WT/MT and the PCR for HBV DRT detected WT. In the remaining 6.9% (5/72) of samples, Sanger sequencing detected WT but PCR for HBV DRT detected MT.

CONCLUSIONThe PCR for HBV DRT showed high sensitivity and accuracy in detecting antiviral drug-resistant mutations. The method is superior to Sanger sequencing for detecting minor mutations and can be used for early detection of a resistance mutation.

Antiviral Agents ; Base Sequence ; Drug Resistance, Viral ; Hepatitis B virus ; Humans ; Mutation ; Plasmids ; Polymerase Chain Reaction ; Sequence Analysis, DNA

Objective To develop nurses'knowledge,attitude and practice questionnaire on medication management for patients with dysphagia,and test its reliability and validity.Methods Based on the evidence-based summary of the best evidence of medication management for patients with dysphagia,guided by the the-ory of knowledge,attitude and practice,the basic dimensions and item pool of the questionnaire were deter-mined through group discussion,Delphi expert consultation and pre-investigation.In order to revise the ques-tionnaire,437 nurses from 10 tertiary hospitals in Jiangsu Province were conveniently selected for investigation,and the reliability and validity of the questionnaire were tested according to the survey results.Results The nurses'knowl-edge,attitude and practice questionnaire on medication management for patients with dysphagia included 43 items in three dimensions.The three dimensions were analyzed by exploratory factors,and six common factors with characteristic roots>1 were extracted.Two factors were extracted from the knowledge dimension,and the cumulative variance contribution rate was 74.958%,One factor was extracted from the attitude dimen-sion,and the cumulative variance contribution rate was 77.655%.Three factors were extracted from the prac-tice dimension,and the cumulative variance contribution rate was 72.274%.The factor load of each item was 0.618-0.902,Cronbach's α coefficient of the total questionnaire was 0.949,and the test-retest reliability was 0.909.The overall content validity coefficient of the questionnaire was 0.922,and the content validity coeffi-cient for each item was 0.800-1.000.Conclusion The nurses'knowledge,attitude and practice questionnaire on medication management for patients with dysphagia developed in this study has good reliability and validi-ty,and could be used as an effective tool to evaluate the status quo of nurses'medication management for pa-tients with dysphagia.

Cognitive dysfunction refers to dysfunction of individual perception,memory,understanding,learning,creation and other dysfunctions caused by abnormal brain function and structure.Based on the fact that the spleen can't regulate transportation and transformation,govern blood and send up essential substance,combined with the microbiota-gut-brain axis,this article discussed the etiology and pathogenesis of intestinal flora imbalance affecting cognitive dysfunction in TCM.It was proposed that the spleen in TCM and intestinal flora are connected in physiology and pathology:the spleen regulates spirit and governs cognition,when the spleen fails to function normally that it can't dominate transportation and transformation,govern blood and send up essential substance will cause that the brain spirit can not be nourished;intestinal flora is closely related to the spleen in TCM,and affects brain function through the nervous system,endocrine,immune and metabolic mechanisms.This article can provide explore new ideas for the clinical research and treatment of cognitive dysfunction of traditional Chinese and Western medicine.

OBJECTIVETo investigate the protective effects on allografts and the possible mechanism of adeno-associated heme-oxygenase-1 (AdHO-1) gene therapy against chronic rejection injury.

METHODSEx vivo AdHO-1 gene therapy was performed in vascular and renal transplantation models. The structure and function, the expression of therapeutic genes and proteins, and the immune modulation were analyzed.

RESULTSAdHO-1 gene therapy protected renal transplant against chronic rejection, but the effect was not as remarkable as that in vascular transplant. The transfected empty vehicle aggravated chronic rejection damage in renal transplantation. AdHO-1 decreased the infiltration of macrophages and CD4(+) T cells.

CONCLUSIONSAdHO-1 gene therapy can lessen damage of chronic rejection in allografts. It plays roles by protecting transplants, down-regulating immune response and inducing immune deviation.

Adenoviridae ; genetics ; Animals ; Blood Vessels ; transplantation ; CD4 Lymphocyte Count ; Chronic Disease ; Genetic Therapy ; methods ; Genetic Vectors ; Graft Rejection ; etiology ; prevention & control ; Graft Survival ; Heme Oxygenase-1 ; genetics ; Kidney Transplantation ; adverse effects ; methods ; Macrophages ; pathology ; Male ; Rats ; Rats, Inbred Lew ; Transfection ; Transplantation, Homologous

OBJECTIVETo study a Chinese pedigree with Hailey-Hailey disease (HHD) and examine the ATP2C1 gene mutation in this family.

METHODAll exons of ATP2C1 gene were analyzed with polymerase chain reaction and DNA sequencing in all patients of this family and 100 unrelated population-match controls.

RESULTSWe identified a novel heterozygous nucleotide A --> G transition at position 235 - 2 in intron 3 of ATP2C1 gene. This splice site mutation was not found in the healthy members of this pedigree and in the controls.

CONCLUSIONThe splicing mutation can affect the result of transcription and translation, and it is a specific novel mutation of ATP2C1 gene.

Asian Continental Ancestry Group ; Calcium-Transporting ATPases ; genetics ; Humans ; Mutation ; Pedigree ; Pemphigus, Benign Familial ; genetics

China’s chronic disease management suffers from problems such as unclear institutional function， insufficient information technology application， and weak regulation support. On the basis of current chronic disease management condition in China， this paper proposes to apply the concept of “people-centered” integrated health management to community chronic disease management and discusses the content and procedure of establishing an integrated community-based chronic disease management model driven by massive databases. The model innovatively combines technology integration， data integration and service integration， and can accurately and efficiently realize the "people-centered" full-course health management of various chronic diseases. Shanghai has provided integrated community-based chronic disease management service for 1.98 million citizens through applying this model. The model warrants further effectiveness and economic evaluation. This study provides precious experience for the development of chronic disease prevention and treatment in China.