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

[Objective]To analyze the prognostic factors of resectable acral melanoma patients ,then develop a novel prognostic model and examined its prognostic value.[Methods]The study retrospectively analyzed clinicopathological characteristics and inflam?matory markers of 232 acral melanoma patients who underwent radical surgical resection between 2000 and 2011 at the Sun Yat-sen University Cancer Center. Kaplan-Meier curves were plotted to estimate overall survival. Significantly predictive factors were identified by multivariate Cox regression analyses and a prognostic model based on these variables was constructed to predict survival.[Results]Cox regression analysis revealed that age,lactic dehydrogenase(LDH),stage,globulin(GLB)and C-reactive protein (CRP)were independently related to survival. After computing these scores ,patients were classified into three risk groups. The new prognostic model identified three categories of patients with different prognoses(P<0.001)and significantly stratify patient prognosis in different tumor stages. The 5-year survival rate was 42.9%,25.7%,and 3.7%in groups 1,2,and 3,respectively. The AUC of new prognostic model is 0.664(95%CI:0.599-0.724).[Conclusion]Age,LDH,stage,GLB and CRP were independently related to survival in our study population,and the prognostic model is useful to stratify patients into different risk groups and it is a useful complement to AJCC staging for Asian patients with acral melanoma.

Objective To evaluate the efficacy of haploidentical hematopoietic stem cell transplantation (HSCT) with supplemental umbilical cord blood (UCB) infusion in treatment of malignant hematological diseases.Method Clinical data of 66 patients with hematological malignancies treated with HSCT in our hospital between January 2010 and May 2013,were retrospectively analyzed.Among them 25 cases received infusion of human UCB before HSCT (experimental group) and other 41 cases had no UCB injection before HSCT (control group).Results There were no differences in age,gender,donor type,disease categories,disease status before transplant between two groups (P ＞ 0.05).There was a significant difference in conditioning regimes between two groups (P ＜ 0.05),but no clinical implication.The infused mononuclear cell (MNC) count in experimental group was higher than that in control group (9.94 ± 2.88 × 108/kg vs.7.80 ±0.82 × 108/kg,P =0.00),while there were no difference in infused CD34 + cell count (5.46 ±3.54 × 106/kg vs.3.54 ± 1.60 × 106/kg,P =0.16).Neutrophil recovery time in experimental group was shorter than that in control group (13.7 ±2.9 d vs.16.6 ±2.9 d,P =0.023).The incidences of grade Ⅲ-Ⅳ acute graft versus host disease (aGVHD,P =0.036),bacterial infection (P =0.001) and fungal infection (P =0.001)and hemorrhagic cystitis (P =0.00)in experimental group were lower than those in control group.There were no significant differences in platelet recovery time(P =0.43),the incidence of grade Ⅰ-Ⅱ aGVHD (P =0.27),implanted syndrome (P =0.24),sinusoidal obstruction syndrome (P =0.57)and viraemia (P =0.31)between two groups.Conclusion HSCT with supplemental infusion of human UCB may alleviate the degree of aGVHD,but the long-term outcome remains to be studied.

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