OBJECTIVE:To study the relevance between the distribution of chain drug stores and medical institutions in Shanghai.METHODS:Taken the density of chain drug stores and medical institutions as index for the description of their distribution,and both non-parametric and parametric methods were applied in the relationship analysis.RESULTS:It was found that the density of chain drug stores and that of the medical institutions were in nonlinear and concaved downward re?lationship.CONCLUSION:The study suggested that currently the distribution of chain drug stores in shanghai is incongruous with the competition pressure from hospital pharmacies.

OBJECTIVE:To summarize the experiences of Ningxia's drug tender policy reform in unifying tender operation,price,and distribution("Trinity" reform).METHODS:Review of the reform process with discussion from the perspective of extension of tender policy objective,essential medicine policy as well as existing problems and corresponding countermeasures.RESULTS & CONCLUSIONS:In addition to the functions that Ningxia's "Trinity" reform of drug tender policy solidifies the price-lowering role of drug tender policy and benefits the construction of essential medicine policy,the reform still needs to be improved with regards to some existing problems.

Adolescent ; Child ; Child, Preschool ; Female ; Hepatocyte Growth Factor ; metabolism ; Humans ; Kidney ; metabolism ; pathology ; Male ; Nephrotic Syndrome ; metabolism ; pathology ; Proto-Oncogene Proteins c-met ; metabolism

ABCC8,KCNJ11,and GLUD1 gene mutations were investigated in a male patient with congenital hyperinsulinism and his parents were also investigated.A 1484 G＞A mutation was found in the 10th exon of ABCC8 gene in the patient,which leads to amino acid substitution at the 495 residue of the sulphonylurea receptor SUR1 protein.The patient's father also carried the same heterozygous inactive mutation,while the genotype of the mother was normal,indicating that the gene mutation of the patient was paternally inherited.According to that mutation,it is deduced that the patient may suffer from the focal type of congenital hyperinsulinism.

Objective To compare the dissolution behavior between domestic trepibutone tablets and original reference product, and provide a basis for evaluating the quality consistency of generic drugs. Methods Four dissolution media recommended by Japanese Orange Book and a domestic standard dissolution media were selected to determined the dissolution profile,and f2 factor was calculated to investigate the consistency of stripping curves. Results In water,pH 4.0 and pH 1.2,the f2 of domestic formulation and reference formulation was under 50,and the dissolution profile was inconsistent.Dissolution behavior of domestic preparations of different manufacturers was dissimilar.In water,the f2 of domestic preparations of different batches of the same manufacturer was over 99.9,and the dissolution behavior was similar. Conclusion The dissolution method of existing domestic standard can not distinguish the dissolution behavior of different products,and it should be revised and completed.There is still great difference in quality between the domestic preparations and reference preparations.

Objective:To establish mice models of Staphylococcus aureus bloodstream infections so as to investigate the inflammatory responses and histopathological changes in bloodstream infections (BSIs) mice.Methods:C57BL/6 mice were inoculated with S.aureus intravenously or intraperitoneally to induce BSIs.Survival rate , weight loss and murine sepsis scores ( MSS ) were ob-served.Blood samples and tissue homogenates were plated on agar to determine bacterial burden .Inflammatory proteins ( CRP,PCT) and cytokines ( IL-1β, IL-6 and TNF-α) were determined by ELISA kits.Histopathologic changes were also assessed by pathological inflammation scores(PIS),macroscopic and microscopic examination.Results: About 70% survival rate was observed in 4.5×108 CFU/ml S.aureus induced BSIs mice.Body weight decreased and sepsis scores increased significantly since 24 h post-infection in BSIs mice,and more prominent in IV group.The counts of WBC began to significantly increase at 3 h post-infection,while CRP and PCT levels peaked at 48 hours in IV and IP groups ( 60.80 ±5.63 vs 40.58 ±7.54 for CRP;6.796 ±1.16 vs 2.740 ±0.36 for PCT ) . Moreover,the levels of IL-1β,IL-6 and TNF-αin serum and tissue homogenates ( liver,lungs,and kidneys ) were significantly elevated in BSIs mice.Pathological changes in tissues (liver,lungs and kidneys) and higher pathological inflammation scores (PIS) were also observed in BSIs mice.Conclusion:Our study represents an effective approach for S.aureus BSIs model to mimic human sepsis.Our results demonstrated that inflammation protein (PCT,CRP) and cytokines(IL-6,IL-1βand TNF-α) play an important role in the in-flammatory response and histopathological changes during BSIs caused by S .aureus.

Objective 99Tcm-4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime(HL91),a new type of hypoxic agents,accumulates in tumor hypoxic tissue specifically.The aim of this study was to evaluate the value of 99Tcm-HL91 imaging in the diagnosis of bone metastasis.Methods Nineteen cases with bone metastasis(without any treatment)and 8 cases with benign lesions underwent SPECT imaging at 4 h after injection of 740 MBq of 99Tcm-HL91 along with 99Tcm-methylene diphosphonic acid(MDP)imaging.Regions of interest(ROIs)were drawn in tumor tissue and contralateral normal tissue respectively,and the radioactivity ratios of tumor-to-normal(T/N)were calculated.The t-test was used for data analysis with SPSS 11.0.Results There were visible uptake of 99Tcm-HL91 in 79 out of 85 focuses in 19 patients of bone metastasis;however,there was no obvious uptake of 99Tcm-HL91 in 12 focuses of 8 patients of benign lesions.Significant difference existed between the T/N values of malignant(1.877±0.288)and benign lesions[(0.735±0.236);t=13.065,P＜0.05].However,the T/N value of bone metastasis from lung cancer did not differ with that from prostate cancer(1.915±0.344 and 1.825±0.175,respectively;t=1.378,P＞0.05).Conclusion The results indicated that 99Tcm-HL91 was useful in diagnosing the malignant and benign bone lesions.

OBJECTIVETo explore the effects and molecular mechanisms of rhein on reducing starvation-induced autophagic protein expression in renal tubular epithelial ( NRK-52E) cells.

METHODHank's balanced salt solution (HBSS) was used to induce NRK-52E cells to be in the state of starvation. After the intervention of HBSS for 0, 0.5,1, 2 and 6 hours, firstly, the protein expression of microtubule-associated protein 1 light chain 3(LC3 I/II), which is a key protein in autophagy, was detected. Secondly, the protein expressions of mammalian target of rapamycin (mTOR) and phosphorylated-mTOR Ser2448 (p-mTOR S2448) were examined. And then, after the co-treatment of rhein (5 mg x L(-1)) and HBSS (1 mL) without or with mTOR inhibitor, rapamycin (100 nmol x L(-1)), the protein expressions of LC3 I/II, mTOR and p-mTOR S2448 were tested, respectively.

RESULTHBSS could induce the up-regulation of LC3 II and the down-regulation of p-mTOR S2448 at protein expression level in NRK-52E cells. The co-treatment of rhein and HBSS could reversely regulate the protein expressions of LC3 II and p-mTOR S2448 in NRK-52E cells significantly. The co-treatment of rapamycin, rhein and HBSS could recover the level of LC3 II protein expression in HBSS-intervened NRK-52E cells.

CONCLUSIONHBSS induces autophagy in renal tubular epithelial cells by inhibiting mTOR signaling pathway activation. Rhein reduces the autophagic protein expression in renal tubular epithelial cells through regulating mTOR signaling pathway activation, which is the possible effects and molecular mechanisms.

Animals ; Anthraquinones ; pharmacology ; Autophagy ; drug effects ; Cells, Cultured ; Epithelial Cells ; drug effects ; metabolism ; Isotonic Solutions ; pharmacology ; Kidney Tubules ; drug effects ; metabolism ; Microtubule-Associated Proteins ; genetics ; Rats ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; antagonists & inhibitors ; genetics ; physiology

To explore novel coumarin derivatives with more potent anti-proliferative activity, a series of novel compounds were designed and synthesized by linking Schiff base and N, N-bis (2-chloroethyl) amine pharmacophore of nitrogen mustards to the coumarin's framework. Their structures were confirmed by 1H NMR, MS and element analysis techniques. In vitro anti-proliferative activities were evaluated against HepG2, DU145 and MCF7 cell lines by the standard MTT assay. The results showed that some of the target compounds exhibited strong anti-proliferative activities against selected tumor cells, and compounds 7c, 7f, 7g, 7h and 7q were better than or equal to the activities of positive control, they deserved further development.
Antineoplastic Agents ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Coumarins ; chemical synthesis ; pharmacology ; Drug Design ; Drug Screening Assays, Antitumor ; Humans ; Nitrogen Mustard Compounds ; chemical synthesis ; pharmacology ; Schiff Bases ; Structure-Activity Relationship

OBJECTIVETo explore the regulative effects and possible mechanisms of emodin on autophagy induced by starvation in rat's renal tubular epithelial cells (NRK-52E).

METHODFirstly, Hank's balanced salt solution (HBSS) was used to induce starvation and the protein expression of microtubule-associated protein 1 light chain 3 (LC3) I/II, an autophagic marker of mammalian congener, was detected by Western blot with or without the treatment of emodin. Secondly, the changes of red fluorescent protein-microtubule associated protein light chain3 (RFP-LC3) fluorescent particles, treated by HBSS (1 mL) and bafilomycin A1 (10 nmol x L(-1)) with or without emodin, were observed through fluorescence microscopy in NRK-52E cells transient transfected by RFP-LC3 plasmid. With the intervention of mammalian target of rapamycin mTOR inhibitor rapamycin (100 nmol x L(-1)) , the effect of blocking mTOR signaling pathway on autophagic inhibition of emodin was observed. Finally, the effect of mTOR signaling pathway on autophagic inhibition of emodin was further evaluated through the over-expression of endogenous mTOR inhibitory protein DEP domain-containing mTOR-interacting protein-(DEPTOR).

RESULTHBSS hunger could induce high protein expression of LC3 II in NRK-52E cells, and the intervention of emodin could reverse the unregulated protein expression of LC3 II induced by HBSS. The number of RFP-LC3 fluorescent particles was increased after the co-treatment of HBSS and bafilomycin A1, and this increase was inhibited by emodin. After the co-treatment of rapamycin, emodin and HBSS, the LC3 II protein expression restored in NRK-52E cells, compared with the treatment of HBSS. Over-expression of DEPTOR could also block the inhibitive effect of emodin on LC3 II protein expression.

CONCLUSIONEmodin could inhibit HBSS-induced LC3 II protein expression and the activation of autophagy in NRK-52E cells, and the effect of blocking autophagy may be mediated through mTOR signaling pathway.

Animals ; Autophagy ; drug effects ; Cell Line ; Down-Regulation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Emodin ; pharmacology ; Isotonic Solutions ; adverse effects ; Kidney Tubules ; cytology ; drug effects ; metabolism ; Microtubule-Associated Proteins ; genetics ; metabolism ; Rats ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; genetics ; metabolism