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

OBJECTIVETo evaluate the accuracy and safety of pedicle screw insertion with the aid of novel patient-specific drill-guide templates in scoliosis cases.

METHODSTen patients with scoliosis were selected to participate in the research (the observation group) from December 2013 to December 2014. The data was obtained from CT scanning, and put into the computer to perform reconstruction of spine, simulation of pedicle screw insertion, and design of patient-specific drill-guide templates with software. The templates were made with rapid prototyping technique. After sterilization, the templates were used to aid the pedicle screw insertion intraoperatively. The blood loss, operation duration, change of creatinine level pre- and post-operation, and complications related to pedicle screw insertion were recorded. The location of pedicle screws were graded so as to evaluate the accuracy. A comparative study was then performed with the data of ten scoliosis cases operated with free-hand method during the same period (control group). There were 5 cases of idiopathic scoliosis and 5 cases of congenital scoliosis in the observation group, including 3 males and 7 females. Their average age was 11.9 years old (ranged, 4 to 18 years old), and the average Cobb angle of main curve was 54.9° (ranged, 42.1° to 78.4°). There were also 5 cases of idiopathic scoliosis and 5 cases of congenital scoliosis in the control group,including 2 males and 8 females. Their average age was 12.6 years old (ranged, 6 to 17 years old), and the average Cobb angle of main curve was 56.6° (ranged, 38.2° to 93.4°).

RESULTSA total of 167 pedicle screws were inserted intraoperatively, with 138 screws (82.6%) in grade I, 26 screws (15.0%) in grade II, 4 screws in grade III (2.4%), but no screws in grade IV according to the CT image. There were 29 (17.4%) screws perforated, and 163 (97.6%) screws could be accepted. In the control group, a total of 165 pedicle screws were inserted intraoperatively, with 98 screws (59.4%) in grade I, 39 screws (23.6%) in grade II, 21 screws in grade III (12.7%), and 7 screws in grade IV (4.2%). There were 67 (40.6%) screws perforated, and 137 (83.0%) screws could be accepted. The grade distribution of screw position, ratio of perforated and accepted screws were significantly different between the two groups respectively (Z=-5.013, P=0.000; χ2=9.347, P=0.002; χ2=20.242, P=0.000). The correction rate of Cobb angle were (74.1±10.0)% vs (69.7±17.6)%; blood loss were (455±447) ml vs (415±389) ml; operation duration were (163.5±53.7) min vs (164.0±48.7) min; and the changes of creatinine level pre- and post-operatively were (-5.3±3.2) μmol/L vs (-3.4±3.1) μmol/L; all above data had no significant differences respectively (t=0.696, P=0.496; t=0.214, P=0.833; t=0.022, P=0.983; t=1.375, P=0.192). There were no complications related to pedicle screw insertion in each group.

CONCLUSIONThe novel patient-specific drill guide template can be used to assist the insertion of pedicle screws in scoliosis cases with much higher accuracy than that of freehand method and fair safety.

Adolescent ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Humans ; Male ; Pedicle Screws ; Scoliosis ; surgery ; Tomography, X-Ray Computed

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 effect of NGX6 with 5-Fu on the apoptosis of colon cancer cells. Methods: The NGX6-transfected HT-29 cell line with 5-Fu was used in the test group. HT-29 cell line with 5-Fu and PDTC was used in the control group. The expression of NF-κB was detected by EMSA. The proliferation of HT-29 cell line was assayed by MTT. The effect of NGX6 on the apoptosis was detected by FCM. HT-29 cells were double-stained by PI/Annexin-V and AO/EB and observed by fluorescence microscopy. Results: The expression of NF-κB was inhibited in NGX6 transfected colon carcinoma cell group and in colon carcino-ma cell group treated with PDTC. Treatment with the chemopreventive compounds 5-Fu and PDTC resulted in different responses in the effects of anti-proliferation and induced apoptosis of colon carcinoma cells. There was no significant difference in apoptosis between NGX6-transfected HT-29 call line with 5-Fu and the cells in the control group. NGX6 gene enhanced the effect of 5-Fu on the proliferation and apoptosis of colon carcino-ma cells. Conclusion: NGX6 gene can induce apoptosis and inhibit the proliferation of colon carcinoma cells. NGX6 gene can enhance the effect of 5-Fu on the proliferation and apoptosis of colon carcinoma cells through NF-κB pathway.