BRAF gene has the highest mutation rate and plays an important role in the occurrence,development,invasion and metastasis of melanoma.The frequency of the mutation varies in different clinical phenotypes,clinical pathology classifications and stages of malignant melanoma,which indicate a certain association of BRAF gene with the growth and prognosis judgment in malignant melanoma.BRAF gene mutation is the new direction of treatment in malignant melanoma molecular target therapy.

Background Statins has prominent roles in regulating lipids,anti-inflammation,autoxidation and protecting vascular endothelial cells.Sartans can promote cell growth and the expression of cytokines.Since the pleiotropic effects of statins and sartans on a variety of cell types,it is inferred that the two medicines can delay retinal aging.Objective This study was to explore the anti-aging effect of simvastatin and telmisartan on the physiological aging of retina.Methods Sixty-six three-month-old healthy SD rats were selected in this study,and 6 of them served as the youth group and the right eyeballs were immediately enucleated.The other rats were raised until 9-month-old in the same conditions and then randomly divided into the simvastatin group,telmisartan group and the control group with 20 rats for each group.The simvastatin of 5 mg/kg and telmisartan of 8 mg/kg were given by intragastric administration once a day in the simvastatin group and the telmisartan group until 17-month-old,and the equal amount of normal saline was used in the control group in the same way.The number of survival rats was 12 in the simvastatin group,10 in the telmisartan group and 8 in the control group.The right eyes were enucleated after heart perfusion of 4％ paraformaldehyde solution for the preparation of retinal paraffin sections.Retinal thickness was measured by pathological examination,and the expressions of the retinal neuron markers,including Thy-1,protein kinase C-α (PKC-ot),opsin and rhodopsin,were detected by immunofluorescence technique to evaluate the morphology of retinal ganglion cells (RGCs),bipolar cells as well as the thickness of the outer segment of photoreceptors.Results The retinal structure was clear in the rats of the youth group.However,the RGCs arrangement and inner segment (IS) and outer segment (OS) structure were abnormal in the simvastatin group,the telmisartan group and the control group.Compared with the rats of the youth group,the thickness of outer nuclear layer (ONL),outer plexiform layer (OPL),inner nuclear layer (INL),inner plexiform layer (IPL) and the total thickness of the aging rats were decreased,and the IS/OS thickness was increased in the simvastatin group and the telmisartan group (all at P＜ 0.01).Thy-1 stain showed that the number of RGCs was reduced in the simvastatin group,telmisartan group and the control group compared with the youth group,and that in the simvastatin group was increased in comparison with the control group (all at P＜0.01).PKC-αt stain exhibited that the density of bipolar cells was increased but the axon terminal bouton was declined in the simvastatin group,telmisartan group and the control group compared with the youth group,and the axon terminal bouton was declined in the simvastatin group compared with the youth group and the control group (all at P=0.000).Opsin and rhodopsin stains displayed that the OS thickness was increased in the simvastatin group,telmisartan group and the control group compared with the youth group,and that in the telmisartan group was reduced in comparison with the control group (all at P＜0.01).Conclusions As SD rat aging,retinal thickness is gradually attenuated and the number of RGCs is gradually declined.Although the density of bipolar cells seem to be unchanged,their synaptic connections are decreased and the OS is thicken.Simvastatin and telmisartan can delay retinal senescence by protecting retinal neurons against aging and thinning thickened OS.

Objective To investigate the role of protein O-linked N-acetyl-glucosamine (O-GlcNAc) modification in glutamine-induced improvement in the vascular hyporeactivity in rats with septic shock.Methods Thirty-two adult male Sprague-Dawley rats,aged 2-3 months,weighing 250-300 g,were randomly divided into 4 groups (n =8 each):sham operation group (S group); septic shock group (C group); glutamine group (G group) ; alloxan group (A group).Septic shock was induced by cecal ligation and puncture (CLP).In G and A groups,glutamine 0.75 g/kg was infused intravenously over 30 min at 1 h before CLP,and in addition alloxan 90 mg/kg was infused intraperitoneally in A group.Phenylephrine (PE) 0.5,1.0,2.0,and 2.5 μg/kg was injected intravenously at 20 min intervals at 6 h after CLP and the percentage increase in mean arterial pressure (MAP) was calculated.The thoracic aorta rings were isolated to perform the isolated vascular tension experiment.The concentration-response curve of PE was obtained in tension experiments,and the PE maximum efficacy (Emas) and median effective dose ( EC50 ) were calculated.The expression of O-GlcNAc modification and iNOS content in the thoracic aorta were detected in all groups.Blood samples were taken to determine the serum concentration of NO.Results Compared with S group,the percentage increase in MAP and Emax were significantly decreased,while the EC50,serum concentration of NO,and expression of O-GlcNAc modification and iNOS content in thoracic aorta were significantly increased in C,G and A groups ( P ＜ 0.05).Compared with C group,the expression of O-GlcNAc modification in the thoracic aorta was significantly increased,and EC50 was significantly decreased in G group,and the percentage increase in MAP and Emax were significantly increased,while the serum concentration of NO,and content of iNOS in the thoracic aorta were significantly decreased in G and A groups ( P ＜ 0.05).Compared with G group,the EC50,serum concentration of NO,and content of iNOS in the thoracic aorta were significantly increased,while the percentage increase in MAP,Emax and expression of O-GlcNAc modification in the thoracic aorta were significantly decreased ( P ＜ 0.05 ).Conclusion Glutamine improves the vascular hyporeactivity through increasing the level of protein O-GlcNAc modification in rats with septic shock.

Objective:To evaluate the profile esthetics of children with skeletal class Ⅲ malocclusion treated with micro-implant.Methods:20 patients (12 boys and 8girls) aged 11-13 years were treated by micro-implant and maxillary protraction for 8 to 10 months.The profile esthetic indexes were measured on pre-and post-treatment cephalometric radiography.Results:The esthetic of the patients were remarkably improved after treatment.The factors that influence the esthetic index of children were the anteroposterior relationship of the maxilla,the mandible and the thickness of soft tissue.The results were stable 1 year after treatment.Conclusion:Maxillary protraction by micro-implant can improve the profile esthetic of children with Class Ⅲ malocclusion,correct over-bite and over-jet.

Statins are a class of hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors, which are pervasively used to reduce blood cholesterol concentration in hypercholesterolemic patients and prevent cardiovascular diseases in clinic, duo to excellent drug efficiency and good safety. In recent years, increasing evidences have demonstrated that statins have potential anti-tumor effect through inhibiting cancer cells growth, invasion, metastasis, preventing angiogenesis, promoting cancer cells apoptosis and synergetically enhancing the effect of radiotherapy and chemotherapy. However, there are no domestic reports about statins' effect on endometrial carcinoma, additionally, conclusions of related foreign studies are inconsistent. This review summarized the effect of statins on endometrial carcinoma.

OBJECTIVETo investigate the changes in the craniofacial morphology ofdeepbite from childhood to adulthood using cross-sectional methods. To analyze the maxillofacial characteristics of adult deepbite.

METHODSThe sample included 159 children (with average age of 12.47 years old) and 81 adults (with average age of21.76 years old) with class III deepbite. The control group consisted of51 normal individuals (with average age of 18.41 years old). Lateral cephalometric radiographs were taken and recorded in a computer through a scanner. Cephalometric measurements were conducted by using Winceph 7.0 software, and results were analyzed with SPSS 12.0 software.

RESULTSSignificant differences between child and adult deepbite were observed in the following: N-ANS, ANS-Me, A-Ms, A-Ptm, Wits, Mo-Ms, Ii-Ii, A-B plane angle to the mandibular plane angle, Gonial angle, L1 to NB length, overjet, mandibular body to anterior cranial base, Mo-Mi, posterior facial height, U1 to NA length, Pog-Go, Cd-Go, occlusion plane angle to SN, and U1 to SN. In addition, significant differences between adult deepbite and normal occlusion were observed in SNB, ANB, convexity, APDI, ODI, Wits, A-B plane to mandibular plane, Gonial angle, overjet, mandibular body to anterior cranial base, S-Ptm, Mo-Mi U1 to SN; Pog-Go, Cd-Go, posterior cranial base, and occlusion plane to SN and posterior facial height.

CONCLUSIONDeepbite patients have certain growth potential after puberty, but the sagittal relationship of their jaws exhibits no improvement. Adult deepbite patients exhibit significant problems in the vertical and sagittal jaw positions.

Adult ; Bone and Bones ; Cephalometry ; Child ; Cross-Sectional Studies ; Dental Occlusion ; Female ; Humans ; Male ; Mandible ; Sexual Maturation

Background Alkali burn-induced corneal neovascularization(CNV) usually leads to blindness.Recently,study determined that vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(bFGF) were the main regulating factors inducing angiogenesis,and canstatin proteins can inhibit the growth of VEGF and bFGF and thereby inhibit CNV growth.Objective The present study was to investigate the effect of recombinant canstatin protein on mouse CNV induced by alkali burn and its mechanism.Methods CNV models were induced in the right eyes of 40 female BALB/c mice by sticking the 2.0 mm filtering paper with 1 mol/L NaOH at the central cornea for 10 seconds.The animals then were randomized into two groups.Recombinant canstatin protein drops(5 mg/L) was topically administered 4 times daily in the mice of the experimental group,and normal saline solution was used at the same way in the control group.Corneas of the mice were examined under the slit lamp to calculate the CNV area 1 day,3,7,14 days after modeling.The mice were sacrificed at above time points and corneas were obtained.The expressions of VEGF protein and bFGF protein in cornea were detected by Western blot,and the results were analyzed by enhanced chemiluminescence(ECL).The use of the experimental animals complied with the Instructive Notions with Respect to Caring for Laboratory Animals by State Ministry of Science and Technology.Results In 3,7 and 14 days after establishment of models,the area of CNV was (1.98-0.31) mm2,(6.21 ±0.44) mm2 and (9.83±0.72) mm2 in the experimental group,and that in the control group was (2.92 ± 0.41) mm2,(8.04 ± 0.56) mm2 and (11.78 ±0.84) mm2,showing significant reduce in the mice treated with recombinant canstatin protein(t3d =4.332,P=0.005 ;t7 d =11.729,P =0.000 ;t14 d =14.562,P =0.000).Western blot analysis showed that there was significant increase in the gray scale of VEGF protein 1 day,3,7,14 days following alkali burn in the experimental group compared with the control group(t1 d =-3.980,P＜0.001 ;t3d =-10.020,P＜0.001 ;t7d =-4.355,P＜0.001 ;t14 d =-8.156,P＜0.001),and the gray scale of bFGF was significantly ascent at various time points in the the experimental in comparison with the control groups (t1 d =-3.488,P＜0.001 ; t3 d =-2.124,P =0.013; t7 d =-1.977,P =0.028; t14 d =-4.542,P＜0.001).Conclusions Topical application of recombinant canstatin protein drops inhibits CNV growth induced by alkali burn by down-regulating the expressions of VEGF and bFGF proteins.

BACKGROUND:Skin-derived mesenchymal stem cels may reflect the onset of psoriasis.
OBJECTIVE:To analyze the biological characteristics of skin-derived mesenchymal stem cels in psoriasis patients.
METHODS:Skin-derived mesenchymal stem cels from 30 patients with psoriasis and 20 healthy controls were isolated and cultured by trypsin. Flow cytometry was used to detect the celular immune phenotypes CD34, CD44, CD29, CD45, CD90, CD105, CD73 and HLA-DR. The mesenchymal stem cels were induced by the corresponding cartilage, osteogenic and osteogenic inducing agents, to identify the multi-directional differentiation ability. The cel proliferation curve was plotted at passage 3, and the levels of transforming growth factor-β1 and epidermal growth factor in culture supernatant were detected by ELISA assay.
RESULTS AND CONCLUSION: Under an inverted phase contrast microscope, primary skin-derived mesenchymal stem cels isolated from patients with psoriasis and normal controls both exhibited heterogeneity. In the two groups, CD29, CD90, CD44, CD73 and CD105 were highly expressed, and CD45, CD34, and HLA-DR were lowly expressed. Under certain conditions, skin-derived mesenchymal stem cels were induced to differentiate into adipocytes, osteoblasts or chondrocytes. Proliferation of skin-derived mesenchymal stem cels in the psoriasis group was significantly faster than that in control group, but the final number of cels in the two groups tended to be consistent. The levels of transforming growth factor-β1 and epidermal growth factor in the psoriatic skinhad no correlation with the severity of the disease (P > 0.05). Compared with the control group, the epidermal growth factor level in the cel supernatant was significantly higher in the psoriasis group (P < 0.01), while the level of transforming growth factor-β1 was significantly lower (P < 0.01). These results showed that there is heterogeneity in the morphology of skin-derived mesenchymal stem cels from psoriasis patients, and the biological activity of mesenchymal stem cels is abnormal.

Objective To investigate the role of epidermal growth factor receptor (EGFR) in the growth and migration of melanoma.Methods A brain-metastatic human melanoma cell line H1,which had been developed in our laboratory,was used in this study.Some H1 melanoma cells were stably transfected with wild-type EGFR via lentiviral vectors to overexpress EGFR (H1EGFRwt),and some H1 cells transfected with green fluorescent protein (GFP) served as the control group (H1GFP).After transfection,the cells were sorted and purified.Then,scratch wound healing assay was performed to estimate the migratory activity of H1 cells; colony-forming assay was conducted to investigate the effects of EGFR on the survival ability and colony-forming ability of H1 cells,and resazurin reduction test was used to evaluate colony formation results; Western blot was carried out to measure the expressions of signaling pathways activated by EGFR.Statistical analysis was done by repeated measures analysis of variance (ANOVA) for the comparison of wound-area healing rate,and by paired t test for the comparison of metabolic activity,between the two groups of H1 cells by using SPSS software version 20.0.Results Flow cytometry showed that H1 cells were successfully transfected with EGFR and GFP respectively,and purified H1EGFRwt and H1GFP cells were obtained after cell sorting.The wound-area healing rate at 6,18,24 and 48 hours after epidermal growth factor (EGF) stimulation was 0.145 ± 0.066,0.479 ± 0.096,0.571 ± 0.198 and 0.672 ± 0.199 respectively for H1EGFRwt cells,0.051 ± 0.036,0.254 ± 0.038,0.303 ± 0.077 and 0.498 ± 0.111 respectively for H1GFP cells.The degree of wound healing in H1EGFRwt cells was significantly higher than that in H1GFP cells (F =68.49,df=5,P ＜ 0.05).Colony-forming assay revealed that the average metabolic activity score of H1EGFRwt cells was significantly higher than that of H1GFP cells (92 225.2 ± 6 632.1 vs.62 935.7 ± 8 159.2,t =2.26,df=9,P ＜ 0.01).Western blot showed that EGF might induce the phosphorylation of downstream signaling proteins such as phosphatidylinositol-specific phospholipase C-γ (PLCγ),signal transducer and activator of transcription 5 (STAT5) and 3 (STAT3) in H1EGFRwt cells,but not in H1GFP cells.In addition,the expressions of phosphorylated serine/threonine protein kinase (pAKT) and mitogen-activated protein kinase (pMAPK) were significantly higher in H1EGFRwt cells than in H1GFP cells after EGF stimulation.Conclusions EGFR may play an important role in the metastasis of H1 melanoma cells,and might serve as a target in the treatment of metastatic melanoma.

0.05). 73.96% of eczema were taken place at the age of 1～6 months, 13.02% were at the age of 6 months to 2 years, and 13.61% were at the age of 2～3 years. The incidence of eczema is also relevant to feeding patterns, which is 62.23%, 23.08% and 14.79% respectively by breast-feeding, mixed feeding and artificial feeding. Some other factors that relevant to the onset of eczema also have been found in the study, such as constitution, weather, genetic background, and so on. Conclusion Feeding pattern, genetic background and some other factors were relevant to the onset of eczema.