Background Econazole nitrate is not effective as an antifungal eyedrop because of its poor intraocular permeability,therefore changing the formulation of econazole nitrate to improve its intraocular permeability become a critical point in the treatment of intraocular fungal infection. Objective The present study was to observe the penetration of 0.5％ econazole nitrate nanoparticles in the corneas and aqueous humors following its topicaladministration. Methods Econazole nitrate nanoparticles were prepared by quasi-emulsion solvent diffusion.Characteristics and size of nanoparticles were examined with transmission electron microscope and laser scatteringmethod,respectively.Econazole nitrate nanoparticles drops (0.5％ )was topically administered in 27 New Zealandwhite rabbits bilaterally,and aqueous humor and corneas were obtained after the application of the eye drops for 5,15,30,45,60,90,120,180,240 minutes respectively to detect the concentration of econazole nitrate with highperformance liquid chromatography (HPLC). The pharmacokinetic parameters were calculated with 3 p97pharmacokinetic computer software.The use of the animals followed the Regulation for the Administration of AffairsConcerning Experimental Animals by State Science and Technology Commission. Results The diameter of thenanoparticles was 50 nm with the round shape and encapsulation efficiency was 96.0％.Econazole nitrate nanoparticlesat the concentration of 0.5％ could be rapidly separated with other elements by HPLC with a lowest quantitativeconcentration of 0.1 mg/L.The mean recovery rates of econazole nitrate nanoparticles were 98.09％ in cornea and 99.66％ in aqueous humor,respectively after topical administration.The peak levels of econazole nitrate nanoparticles in cornea and aqueous humor were achieved at 5 minutes after application ( cornea:40.620 μg/g± 7.756 μg/g;aqueous humor:0.504 mg/L±0.153 mg/L),and its half-life( t1/2 )in cornea and aqueous humor was 23.5 minutes and 18.6 minutes,respectively. Conclusions Econazole nitrate nanoparticles at 0.5％ concentration can remain a feasible bioavailability in ocular tissue and therapeutic level in cornea and aqueous humor.

Objective To investigate the effects of metformin on cell proliferation in differentiation degree of endometrial carcinoma cells and related mechanisms. Methods The endometrial cancer cell lines Ishikawa and AN3CA were used. Cell proliferation was assessed after exposure to metformin with or without epithelial growth factor receptor (EGFR) inhibitor AG1478 by cell counting kit-8 (CCK-8) method. EGFR mRNA was determined by reverse transcription (RT)-PCR. The expression of phosphorylation EGFR (p-EGFR) and total EGFR (t-EGFR) and phosphorylation extracellular signal-regulated kinase 1/2 (p-ERK1/2) and total ERK1/2 (t-ERK1/2) were examined by western blot. Results (1)CCK-8 experiment showed that metformin could inhibit the proliferation of endometrial cancer cells in a time-dependent manner and a dose-dependent manner (P<0.05), but the inhibition of well differentiated cell line Ishikawa was lower than that in poorly differentiated cells AN3CA (P<0.05). AG1478 also could inhibit the proliferation of endometrial cancer cells in a time-dependent manner and in a dose-dependent manner (P<0.05), but the inhibition rate of well differentiated cell line Ishikawa was higher than that in poorly differentiated cells AN3CA (P<0.05). Metformin+AG1478 also could inhibit the proliferation of endometrial cancer cells in a time-dependent manner and in a dose-dependent manner (P<0.05), and the inhibition of combined with metformin and AG1478 was stronger than that with a single application of drugs, but the inhibition rate of Ishikawa was higher than that in AN3CA (P<0.05).(2)RT-PCR method showed that different concentrations of metformin (0.01, 0.1, 1, 5, 10 mmol/L, respectively) for 24 hours, the expression level of EGFR mRNA in Ishikawa cells were respectively 0.74±0.03, 0.61±0.04, 0.46±0.03, 0.31±0.03 and 0.23±0.03, the expression level of EGFR mRNA in AN3CA cells were respectively 0.79±0.20, 0.61±0.03, 0.50±0.05, 0.32±0.03 and 0.26 ± 0.04, the inhibition effect showed a significant concentration-dependent manner (all P<0.01). (3) Western blot method displayed that the effect of metformin treated respectively 2, 4, 6 or 8 hours, there were not significant difference in the expression levels of t-EGFR protein and t-ERK1/2 between Ishikawa and AN3CA cells (all P>0.05). But the expression levels of p-EGFR and p-ERK1/2 protein were significantly lower between two groups (P<0.01), which showed a time-dependent manner(P<0.01). Conclusion Metformin could inhibit the proliferation of endometrial cancer cells, the inhibition is associated with the differentiation degree of cancer cells. Metformin could enhance the EGFR signaling pathway inhibitor AG1478 inhibition of endometrial cancer cells, which may inhibit EGFR expression of phosphorylated proteins to inhibit the phosphorylation of ERK1/2 proteins and then inhibit proliferation of endometrial cancer cells.

Objective To summarize the application of endovascular treatment of the acute ruptured intracranial aneurysms with the new Trufill detachable coil system.Methods Thirty five patients with the acute ruptured intracranial aneurysms were treated with DCS or DCS Orbit within 72 hours. Results All 35 cases were successful with compact embolization in 29 aneurysms,95% in 3 aneurysms,90% in 2 aneurysms,80% in 1 anearysm.One case hemorrhaged during operation and 1 case had thrombosis after operation,but with good prognosis of both.One case died of pneurmonia.Thirty cases achieved clinic follow-up 1 to 15 months after operation with only one rebleeing.Sixteen cases achieved DSA follow-up 3 to 12 months after the operation.Partial recurrence of the occluded aneurysm was shown in 1 case.Conclusions Trufill DCS or DCS Orbit is a safe,reliable and effective therapy for the endovascular treatment of intracraranial aneurysms.

Objective To identify mutations site and clinical characteristics of a familial hypercholesterolemia(FH) proband diagnosed clinically through DNA sequencing and family analysis in the proband and his family members of 3 generations.Methods Blood samples and clinical data of the kindred of total 29 from 3 generations members were collected.Proband had a physical examination electrocar-diogrom and vascular ultrasound.The proband and his family members took routine clinical exams,and genomic DNA was isolated.The promoter region and the 18 exons of low density liporotein receptor(LDLR) gene were screened by Touch down polymerase chain reaction -single strand conformation polymorphism(PCR-SSCP) and DNA sequencing.The result of sequencing were matched gene sequence published in the BLAST database.Results 1.Increased intima-media thickness and plaque were detected in the common carotid artery,right subclavian artery of the proband.Aortic valve regurgitation was found by echocardiography.2.No mutation R3500Q of ApoB100 was observed.3.Two heterozygous mutations in exon 10 and 13 of LDLR gene (W462X and A606T) were identified.The proband and 5 members of paternal relatives showed W462X heterozygosis mutation in exon 10 of LDLR gene which introduced the change from tryptophone to a new stop codon.The proband's mother and grandmother harboured A606T heterozygous mutation in exon 13 of LDLR gene due to a single base pair substitution of G for A in the codon for residue 1 879.Conclusions Disease causing mutations of proband are W462X and A606T compound heterozygosis mutation in exon 10 and 13 of LDLR gene inherited from mother and father.Proband shows homozyous phenotype though the genotype analysis indicates heterozygous mutations.

Animals ; Disease Models, Animal ; Hypoglycemia ; chemically induced ; metabolism ; Hypothalamus ; drug effects ; metabolism ; Insulin ; pharmacology ; Intracellular Signaling Peptides and Proteins ; metabolism ; Male ; Neuropeptides ; metabolism ; Orexins ; Rats ; Rats, Sprague-Dawley

Objective To explore the possible mechanism and protective effect of Xuebijing injection (血必净注射液)and dexamethasone on rats with paraquat-induced chronic pulmonary injury.Methods Thirty male Wistar rats were randomly divided into six groups:normal group(n=5),model group(n=5), treatment groups(n=20).In the normal group,normal saline was used,while in the other groups,20% paraquat 80 mg/kg was injected peritoneally for poisoning.After 2 hours of intoxication,low dose Xuebijing injection(1.25 g/kg),high dose Xuebijing injection(2.50 g/kg),dexamethasone(25 mg/kg),high dose Xuebijing injection combined with dexamethasone(combined group)respectively were administered into the four different treatment groups,equal amount of normal saline was given to the normal and model groups,and the treatment continued for 4 days.At 28 days after paraquat injection,5 rats in each group were killed respectively,serum transforming growth factor-?1(TGF-?1)and hydroxyproline(HYP)level in the lung homogenate were measured,and pulmonary coefficient and histological changes were observed.Results In the treatment groups,the levels of serum TGF-?1 and lung tissue HYP,pulmonary coefficient were leas than those of model group,and among the treatment groups,combined group had the best results(all P

Female ; Humans ; Infant, Newborn ; Maple Syrup Urine Disease ; diagnosis ; therapy

CDISC standard has become a set of global data standards that can be used in clinical study, covering the full life cycle of clinical researches. After nearly 20 years of development and continuous version upgrades, CDISC standard can improve the quality and efficiency of clinical research and drug review, and to facilitate all stakeholders involved in researches to exchange the study data and communicate the outcomes. CDISC standard has been or is to be adopted as standard format in data submission by multiple regulatory authorities, and more widely implemented by the global pharmaceutical community. CDISC standard is gradually adopted in China. The feasibility and roadmap of CDISC standard as the Chinese data submission format requirements are undergoing exploration and piloting further.
Biomedical Research ; standards ; China ; Clinical Trials as Topic ; standards ; Data Collection ; standards

Objective To identify histopathologic correlates for the various MRI appearances of breast fibroadenomas.Methods Thirty-eight fibroadenomas in 33 patients(aged 24—57 years)examined with gadolonium-enhanced MR imaging were observed for signal intensity on T_2-weighted images,contrast enhancement,shape,and internal septation,and these findings were correlated with histopathologic findings.All cases underwent surgery and were proved by pathology.Results(1)The lesion shape was lobular,or round in 34 of 38 fibroadenomas(89.5%).(2)The signal intensity on T_1-weighted images was less than or equal to that of fibroglandular tissue in all cases.The signal intensity on T_2-weighted images was highly varible:high T_2 signal intensity was associated with more myxomatous stromal(mean myxoid-sclerotic index value of 1.9),higher stromal cellularity(mean stromal cellularity index value of 2.2); Fibroadenomas with low T_2 signal intensity had stromal that was nearly uniformly sclerotic(mean myxoid- sclerotic index values of 2.8)and low stromal cellularity(mean stromal-cellularity index value of 1.2). Significant differences were found between these two groups,x~2=11.267 and x~2=10.415(P0.05).The degree of contrast enhancement was proved to be related to ages of patients.The enhancement was more intensely in younger patients.(5)Internal septations were identified within nine of 33 enhancing fibroadenomas (27.3%)and appeared to correlated with collagenous bands at histopatholigic analysis.Conclusions Fibroadenomas demonstrate marked histopathologic variability.The resultant variability in the MR appearance correlated with the degree of myxomatous or sclerotic and stromal cellularity.Lobulation and internal septation,which appear to reflect intrinsic growth patterns of fibroadenomas,may provide more reliable information for distinction.Familiarity with the diagnostic features would facilitate to make the differential diagnosis correctly.

Objective　To explore the relationship between angiogenesis and tumor metastasis and prognosis by studying the angiogen esis in colorectal carcinoma tissues and metastasized tissues. Me thods　The microvessel density (MVD) and the expression of vascular endo thelial growth factor (VEGF) were studied with immunohistochemical assays in 15 samples of colorectal carcinoma with lymph node and liver metastasis, 20 specime ns of colorectal carcinoma without metastasis. Normal rectal mocosal tissues wer e taken from 10 cases of colorectal carcinoma with metastasis and 10 without.Re sults　The MVD was obviously higher in the cases of colorectal carcinoma with or without metastasis than in normal rectal tissues, and that in those wit h metastasis was higher than that of those without. The MVD was significantly hi gher in those positive to VEGF staining than those negative in colorectal carcin oma tissues and metastasized tumors. Conclusion　The MVD and VEG F expression can be regarded as indexes for tumor metastasis and prognosis in co lorectal carcinoma.