Leber congenital amaurosis (LCA) is one of the main inherited retinal diseases causing congenital blindness.LCA is also characterized by genetic heterogeneity and variable clinical phenotypes.Recent years,a lot of molecular genetic studies related with its pathogenesis have been performed.So far,20 causative genes have been identified that account for LCA.Some correlations between genotype and clinical phenotype have also been found.Those specific clinical manifestations may help to identify the mutant gene that causes the LCA.This review summarized the causal genes,their roles in the pathogenesis of LCA,coupled with relationship between specific gene and Corresponding phenotype,which will assist the clinician in patient diagnosis and counseling.

Abstract? AIM: To analyze the ocular manifestations of meningiomas in the trigone of the lateral ventricle, discuss the relevant factors of visual impairment in these patients and things need attention clinically.?METHODS:Retrospectively study on the clinical data of 90 eyes in 45 patients diagnosed of trigonal meningiomas treated at Beijing Tian Tan Hospital from October 2011 to October 2015.Preoperative examinations including visual acuity, optic disc findings, visual field, size of tumors and other change in MRI were analyzed.?RESULTS: Patients'age was 12-68 years old ( mean 41.7 ±13.7 years ). Male/female ratio was 1 ∶4.6. Decreased visual acuity occurred in 18 eyes.Optic disc edema was found in 24 eyes and optic disc pale in 6 eyes. Fourty -seven eyes had visual field defect, mostly homonymous hemianopia or defect. The maximum diameter of tumors was 2.1-9.6cm (4.8±1.7cm).Range of tumor volume was 3.02-193.2cm3(48.3±47.8cm3).A positive correlation of preoperative visual field defect was found with tumor volume, tumor maximum diameter, and brain midline shift respectively. While the preoperative visual field defect was not found any correlation with age, gender, course, and the enlargement of the ventricle and the edema of the tissue around the tumors. After Mann-Whitney U test, the differences on tumor volume, the maximum diameter of tumors, and brain midline shift between the two groups were significant.? CONCLUSION: Patients with trigonal meningiomas often have ocular signs and symptoms.The major reason of visual field defect is the damage of optic radiation around the tumor.The specific position of injured optic radiation determines the type and extent of visual field defect.Both ophthalmologist and neurosurgeon should pay attention to tumors nearby posterior visual pathway. Doing neurophthalmology examinations for these patients and realizing the position between the tumor and posterior visual pathway will be helpful and necessary in surgical planning.

At the moment,neural stem cells(NSC)therapy is one of the main means to improve stroke and neurodengenera?tive disease. This paper analyses the key molecular targets that promote NSC migration,such as chemokines,brain-derived neuro?trophic factor and vascular endothelial growth factor,and clarifies the relationships as well as important nodes between pathways,like PI3K/Akt,MAPK/ERK,and JAK/STAT.It is helpful to understand the molecular network mechanisms of NSC migration and provide ideas and targets to design creative drugs to promote NSC migration.

ObjectiveTo determine the serum MDA5 levels and their clinical associations in patients with polymyositis/dermatomyositis (PM/DM).MethodsSerum anti-MDA5 antibody was detected by ELISA in 119 adult PM/DM patients,30 patients with systemic lupus erythematosus(SLE),30 patients with rheumatoid arthritis (RA),15 patients with primary Sj(O)gren's syndrome (SS),21 patients with pulmonary infection and 50 healthy controls.t-test,Mann-Whitney U test or chi-square test or Fisher exact test as well as Logistic multivariate regression analysis were carried out to compare the results of this study.ResultsSerum antiMDA5 antibody positive rate in DM patients(22.6％) were significantly higher compared with that of patients with PM (0,P＜0.01),patients with SLE (3.3％,X2=5.68,P＜0.05),RA (3.3％,X2=5.68,P＜0.05),pSS (0,P＜0.05) and pulmonary infection(0,P＜0.05) and healthy controls (0,P＜0.01).In the DM subgroup,CADM patients presented a higher positive anti-MDA5 antibody rate than classic DM patients.The incidence of arthritis,fever,vrash raised CEA and CA153 level,and serum concentration of GGT and ferritin were significantly higher in the anti-MDA5 positive DM group than anti-MDA5 negative DM group (X2=4.08,8.06,6.357,32.4,4.867; Z=-2.86,-2.44; P value of all these tests were less than 0.05 ),while the rate of serum positive ANA,serum level of CK and T,NK cell counts in the peripheral blood were much lower than those in anti-MDA5 negative DM group(X2=4.08; Z=-2.072,-2.013,-2.907; all P＜0.05).Moreover,the incidence of acute/subacute interstitial pneumonia(A/SIP) was significantly higher in anti-MDA5 positive DM patients than anti-MDA5 negative DM patients.The sensitivity and specificity of anti-MDA5 antibody for diagnosing A/SIP in DM patients were 88.2％ and 94％ respectively.Additionally,logistic multivariate analysis showed that anti-MDA5 was an independent risk factor for death of interstitial lung diseases (ILD) in DM (OR=8.46,95％CI 1.77～40.36,P＜0.01).ConclusionIn Chinese PM/DM patients,serum anti-MDA5 antibody is mainly present in DM patients and is a strong predictor for poor prognosis diagnosis of DM with A/SIP and is an independent risk factor for death of ILD in DM.

OBJECTIVETo evaluate the effect of melittin and 5-Fu, DDP, and TXT on human gastric cancer cell line BGC-823 and to primarily explore their possible mechanisms.

METHODSMedian effect analysis was employed to determine the interaction between melittin and 5-Fu, DDP, TXT by analyzing the relationship between fraction affected (FA) and the combination index (CI) acquired from the dose-effect curve. Expressions of chemotherapeutic agent-associated genes of BGC-823 cells with or without treatment were measured by real-time fluorescent quantitative PCR.

RESULTS(1) Both melittin and chemotherapeutic agents inhibited the growth of BGC-823. (2) For BGC-823 cells were acted by 5-Fu +melittin, when FA ranged between 0.35-0.75, CI was less than 1. For BGC-823 cells were acted by DDP + melittin, when FA ranged 0.55 or so, CI = 1; when Fa ranged below 0.55, CI was less than 1. For BGC-823 cells were acted by TXT + melittin, CI less than 1 could be seen in the whole interval. (3) After treatment suppressed were the expressions of chemotherapeutic agent-associated genes of BGC-823 cells such as thymidylate synthetase (TS), excision repair cross-complementing gene 1 (ERCC1), breast cancer susceptibility gene 1 (BRCA1), beta-tubulin III (TUBB3), and microtubule-associated protein tau (MAPT).

CONCLUSIONSMelittin had a synergistic effect on the cytotoxicity of chemotherapeutic agents. The possible mechanisms might be associated with down-regulating chemotherapeutic agent-associated genes.

Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Synergism ; Fluorouracil ; pharmacology ; Humans ; Melitten ; pharmacology

Background Pathologic myopia is one of the common blinding eye diseases.Recent research suggests that immune response participates in the pathogenesis of pathologic myopia,and inflammation is an important factor that influent immune status.Objective Present study was to observe the change of high sensitive C-reactive protein(hs-CRP) in serum in the patients with pathologic myopia and explore the role of inflammation in the development of pathologic myopia. Methods Serum hs-CRP was measured from 30 patients with pathologic myopia,30 patients with simple myopia and 30 normal controls with Nephelometric Turbidity in the OLYMPUS AU5400 automatic biochemical analyzer.Written informed consent was obmined from each subject before medical examination.Results The mean age was(30+10) years in pathologic myopia group,and(32+8)years in simple myopia group and(32+9)years in normal control group.The range of preoperative spherical equivalent refraction was (-6.00--22.00) D in pathologic myopia group,(-1.00--6.00) D in simple myopia group and(-1.00-+1.00) D in normal control group.The level of hs-CRP in serum was(3.68±1.15)mmol/L in the patients with pathologic myopia and was significantly higher than that of simple myopia group(1.99±0.68 mmol/L)and normal controls (2.11±O.66 mmol/L)(q=10.69,P＜0.01;q=9.91,P＜0.01),respectively.No significant correlation was found between hs-CRP level and myopic degrees in pathologic myopia group(R2=0.037,P＞0.05). Conclusion Hs-CRP may play rule in the inflammatory reaction during the pathogenesis of pathologic myopia.

BackgroundDry eye is a multi-factorial-induced tear film and ocular surface disorder.Immunoinflammation plays a key role in the pathogenesis of dry eye.As inhibitor of the cyclo-oxygenase pathway,nonsteroidal anti-inflammatory drugs play an anti-inflammatory and anti-hypersensitivity role,and it can be a potential treatment for dry eyes.ObjectiveThis study was to investigate the effectiveness of nonsteroidal anti-inflammatory drugs (0.1％topical pranoprofen) on moderate to severe dry eyes and its mechanism.MethodsThis was a small sample of randomized controlled clinical trial.Thirty right eyes of 30 patients with moderate to severe dry eyes were included in the study according to the diagnosis criteria and randomized into two groups.The patients of the trial group received topical administration of 0.1％ pranoprofen plus 0.1％ sodium hyaluronate,and those of the control group received the topical 0.1％ sodium hyaluronate only.Ocular surface inflammation index scores (OSDI) and ocular surface fluorescine staining (OSS) scores were measured under the slit lamp,and tear film break-up time (BUT),Schirmer Ⅰ test values were evaluated.The expression of human leucocyte antigen-DR (HLA-DR) and CD11b in conjunctiva epithelial cells were detected by impression cytology and flow cytometry (FCM).All the indexes were compared between the two groups before and after treatment.Informed consent was obtained from all patients.ResultsThere were no significant differences in terms of age and gender and their baseline values between the trial group and control group (t=0.412,P=0.684;x2=0.240,P=0.624),and so were all the indexes (P＞0.05).Compared with the control group,the OSDI,OSS scores and cells positive for HLA-DR were lowered but the BUT was delayed in the trial group on day 15 ( t=2.43,P=0.03;t=2.83,P=0.01;t=3.29,P=0.00;t=3.23,P=0.00 ).No significant differences were found in the Schirmer Ⅰ test value and CD11b expression between these two groups (t=0.17,P=0.87;t=0.28,P=0.79).The OSDI,OSS scores and BUT were significantly improved,and the number of cells positive for HLA-DR were reduced 15 days after administration of drugs in comparison with before treatment in the trial group ( t =12.30,10.70,6.10,7.92,P =0.00 ).However,there were no comparable alteration seen in these indexes before and after the usage of drugs in the control group ( P＞0.05).Positive correlations were found in HLADR expression with OSDI and OSS ( r =0.601,P =0.018 ; r =0.586,P =0.022 ) and a negative correlation in HLADR expression with BUT (r=-0.697,P=0.004) on day 15 in the trial group.ConclusionsTopical usage of 0.1％ pranoprofen is beneficial for remitting the ocular signs and symptoms in moderate to severe dry eyes.This study illustrates that topical usage of 0.1％ pranoprofen can down-regulate the expression of inflammatory markers in conjunctival epithelial cells.

Objective To investigate the risk factors of postmenopausal osteoporosis ( PMOP) in Chongqing region,and provide the theoretical basis for osteoporosis prevention and treatment. Methods A hospital-based case-control study was conducted and standardized questionnaire was applied in this project. All patients were informed of the purpose of this study and signed an informed consent form. The protocol and consent form were approved by the Ethics Committee of Third Military Medical University. Non-conditional logistic model was used to estimate the association between risk factors and PMOP. Results After adjustment for some potential confounding factors,multivariate non-conditional logistic regression analysis indicated that family history of hip fracture ( OR = 8. 567,95% CI 3. 463 to 12. 620) ,lower body mass index ( OR = 3. 081,95% CI 1. 344 to 5. 632) ,and parities ( OR = 2. 539,95% CI 1. 263 to 4. 175) were significantly positive correlated with the incidence of PMOP. However,frequently exercise ( OR = 0. 276,95% CI 0. 152 to 0. 730) ,tea drinking ( OR =0. 354,95%CI 0. 209 to 0. 764) and older at menopause ( OR =0. 621,95%CI 0. 327 to 0. 942) were significantly negative correlated with it. Conclusion Family history of hip fracture,lower body mass index and higher parities are the risk factors of PMOP in Chongqing region. Besides,frequent exercise,tea drinking and proper endogenous estrogen level are the protective factors.

The aim of this study was to investigate the effects of AEG-1 gene silencing on the chemoresistance of human breast cancer cell line MCF-7/ADM and its possible mechanism. MCF-7/ADM cells were incubated in the medium containing adriamycin (ADM). The recombinant pLKO.1-shAEG-1 plasmid was constructed to silence AEG-1 expression in human breast cancer MCF-7/ADM cells. MTT assay was employed to detect the anti-tumor effect of ADM on MCF-7/ADM cells, and IC50 value of ADM was calculated according to MTT. Flow cytometry was used to determine the apoptosis. Western blot was used to analyze the expression levels of AEG-1, p-Akt, p-MDM2, p-Bad, p53 and MDR1. The result showed MCF-7/ADM had a significantly higher expression level of AEG-1 compared with that of MCF-7 (P < 0.05), however, the expression of AEG-1 was decreased after AEG-1 gene silencing. The IC50 value of ADM in shAEG-1 group was significantly lower than that in shcontrol group. AEG-1 gene silencing induced cell apoptosis and enhanced the pro-apoptotic effect of ADM on MCF-7/ADM cells. After AEG-1 gene silencing, the phosphorylation of Akt, MDM2 and Bad was inhibited (P < 0.05), the protein levels of p53 and MDR1 were up-regulated (P < 0.05) and down-regulated (P < 0.05) respectively, compared with control. In conclusion, the results suggest that AEG-1 gene silencing can reverse the ADM resistance in human breast cancer cell line MCF-7/ADM by means of inducing apoptosis and down-regulating the protein level of MDR1.
Apoptosis ; Breast Neoplasms ; genetics ; metabolism ; Cell Adhesion Molecules ; genetics ; metabolism ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; genetics ; Gene Silencing ; Humans ; MCF-7 Cells

BACKGROUNDEpigallocatechin-3-gallate (EGCG) has been demonstrated to have anti-neoplastic activity, but the effective concentration of EGCG and its possible mechanisms are uncertain. The study on the killing effects of EGCG on different digestive tract cancer cell lines can find target sites of its anti-neoplastic effect and provide a theoretical basis for its clinical application in the treatment of cancers.

METHODSMethyl thiazolyl tetrazolium (MTT) analysis was made to detect the differential sensitivities of eight digestive tract cancer cell lines to EGCG. The effect of EGCG on cell cycle distribution of sensitive cancer cell line was measured by flow cytometry. By polymerase chain reaction (PCR)-enzyme linked immunosorbent assay (ELISA) protocol, the influence of EGCG on telomerase activity of sensitive cancer cell line was also investigated. RT-PCR method was employed to detect the influence of EGCG on the expressions of hTERT, c-myc, p53 and mad1 genes in sensitive cancer cell line.

RESULTSEGCG exhibited dose-dependent killing effects on all eight digestive tract cancer cell lines. The 50% inhibitory concentration (IC50) of SW1116, MKN45, BGC823, SGC7901, AGS, MKN28, HGC27 and LoVo cells were 51.7 micromol/L, 55.9 micromol/L, 68.5 micromol/L, 79.1 micromol/L, 83.8 micromol/L, 119.8 micromol/L, 183.2 micromol/L and 194.6 micromol/L, respectively. There were no apparent changes in cell cycle distribution of sensitive cancer cell line MKN45 48 hours after incubating with three different concentrations of EGCG compared with the controls. It was found that EGCG could suppress the telomerase activity of MKN45 cells, and the effects were dose- and time-dependent. After EGCG administration, the expression of hTERT and c-myc genes in MKN45 cells was decreased, that of the mad1 gene increased, and that of the p53 gene unchanged.

CONCLUSIONSEGCG has dose-dependent killing effects on different digestive tract cancer cell lines. Administration of EGCG has no obvious effect on cell cycle distribution of sensitive cancer cell line MKN45. The anti-neoplastic activity of EGCG might be due to the inhibition of telomerase activity by means of its influence on hTERT and the up-stream regulation genes.

Antineoplastic Agents ; pharmacology ; Catechin ; analogs & derivatives ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; DNA-Binding Proteins ; genetics ; Digestive System Neoplasms ; drug therapy ; metabolism ; pathology ; Dose-Response Relationship, Drug ; Genes, myc ; Genes, p53 ; Humans ; Telomerase ; genetics ; metabolism