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Xiao H.,Liaoning Medical University | Xiao H.,463th Hospital of the Peoples Liberation Army | Fan Z.-Y.,463th Hospital of the Peoples Liberation Army | Tian X.-D.,Fourth Peoples Hospital of Shenyang | Xu Y.-C.,Liaoning Medical University
International Journal of Ophthalmology | Year: 2014

AIM To study the efficacy difference between form-deprived myopia (FDM) and lens-induced myopia (L1M), the degree of myopia, axial length and pathological changes of the posterior sclera from guinea pigs were evaluated. METHODS Four-week pigmented guinea pigs were randomly assigned into 3 groups, including normal control (n=6), FDM group with monocular cover (n=i 1) and LIM group with monocular -7Dlens treatment (n=i 1). FDM group was form-deprived while LIM group was lens-induced for 1 4 d. Refractive error and axial length were measured prior to and post treatment, respectively. Morphological changes of sclera were examined using both light and electronic microscopes. RESULTS After 1 4d treatment, refractive errors for FDM group and LIM group were -3 .05 ±0.7 1 D and -2.1 2 ±1.29 D, respectively, which were significantly more myopic than that of normal controls and fellow control eyes (Po.os). Under light microscope, both FDM group and LIM group showed thinned sclera, disarrangement of fibrosis and enlarged disassociation between fibers. Consistently, ultrastructural examination showed degenerated fibroblasts and thinned fibers in posterior sclera. CONCLUSION Following two weeks of myopia induction in guinea pigs, with regard to the degree of myopia, axial length and pathological alterations, there was no significant difference between FDM and LIM models. Therefore, FDM and LIM are equally effective and useful as a model of experimental myopia and guinea pigs are ideal animals for induction of experimental myopia because their high sensitivity to both form-deprivation and lens-induction. © International Journal of Ophthalmology Press.


Tian X.-D.,Liaoning Medical University | Tian X.-D.,Fourth Peoples Hospital of Shenyang | Cheng Y.-X.,Heilongjiang University | Liu G.-B.,Heilongjiang University | And 4 more authors.
International Journal of Ophthalmology | Year: 2013

AIM: To investigate the expressions of type I collagen, α2 integrin and β1 integrin in the posterior sclera of guinea pigs with defocus myopia and whether basic fibroblast growth factor (bFGF) injection inhibits the formation and development of myopia by upregulating the expression of type I collagen, α2 integrin and β1 integrin. METHODS: After 14 days of treatment, the refractive state and axial length were measured and the levels of type I collagen, α2 integrin and β1 integrin were assayed in the posterior sclerae of groups of guinea pigs that wore a monocular-7D polymethylmethacry late (PMMA) lens or had-7 D lens wear followed by the peribulbar injection of Phosphate Buffer Solution (PBS) or bFGF. The untreated fellow eye served as a control. Guinea pigs with no treatment served as normal group. RESULTS: The results showed that 14 days of monocular defocus increased axial eye length and refraction, while bFGF delivery inhibited them markedly. Further, it was also found that the monocular-7D lens could decrease the levels of type I collagen, α2 integrin and β1 integrin expressions, while, unlike PBS, bFGF increased them significantly in comparison to contralateral control eyes and normal eyes. CONCLUSION: bFGF can prevent the formation and development of defocus myopia by upregulating the expressions of type I collagen, α2 integrin and β1 integrin. Taken together, our results demonstrate that bFGF promotes sclera remodeling to prevent myopia in guinea pigs. Copyright International Journal of Ophthalmology Press.


Zhuang X.,Shenyang University | Zhuang X.,Fourth Peoples Hospital of Shenyang | Wang L.,Peking Union Medical College | Wang L.,Central Hospital of Zibo | And 2 more authors.
PLoS ONE | Year: 2015

Objective: To investigate a novel insertion variant of CRYGD identified in a Chinese family with nuclear congenital cataract. Methods: A Chinese family with congenital nuclear cataract was recruited for the mutational screening of candidate genes by direct sequencing. Recombinant N-terminal Myc tagged wildtype or mutant CRYGD was expressed in HEK293T cells. The expression pattern, protein solubility and subcellular distribution were analyzed by western blotting and immunofluorescence. Principal Findings: A novel insertion variant, c.451-452insGACT, in CRYGD was identified in the patients. It causes a frameshift and a premature termination of the polypeptide to become Y151∗. A significantly reduced solubility was observed for this mutant. Unlike wildtype CRYGD, which existed mainly in the cytoplasm, Y151∗ was mis-located in the nucleus. Conclusions: We have identified a novel mutation, c.451-452insGACT, in CRYGD, which is associated with nuclear cataract. This is the first insertion mutation of CRYGD found to cause autosomal dominant congenital cataract. The mutant protein, with loss of solubility and localization to the nucleus, is hypothesized to be the major cause of cataract in these patients. © 2015 Zhuang et al.


Sun L.,Shenyang University | Yuan Q.,Shenyang University | Cao N.,General Hospital of Shenyang Military Command | Guo W.,Fourth Peoples Hospital of Shenyang | And 4 more authors.
Scientific World Journal | Year: 2014

Objective. This meta-analysis aimed to investigate a comprehensive and reliable conclusion on the correlations of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) gene with the risk of diabetic nephropathy (DN) in patients with diabetes mellitus (DM). Methods. We screened PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM, and CNKI databases for those relevant studies that investigated the association of 14,945 subjects with clinicopathological parameters in gastric cancer. Results. Eleven case-control studies that met all inclusion criteria were included in this meta-analysis. A total of 14,945 subjects were involved, including 3,049 DN patients and 11,896 DM patients. Our meta-analysis results revealed that VEGF rs2010963 and rs3025039 polymorphisms might contribute to the risk of DN in DM patients. Ethnicity-stratified analysis suggested that VEGF genetic polymorphisms were associated with an increased risk of DN among Asians. However, we found no correlations of VEGF genetic polymorphisms with susceptibility to DN among Caucasians. Conclusion. Our findings suggest that VEGF rs2010963 and rs3025039 polymorphisms may contribute to the risk of DN in DM patients, especially among Asians. Thus, VEGF genetic polymorphisms could be useful biomarkers for early diagnosis of DN in DM patients. © 2014 Li Sun et al.


Sun X.,Shenyang University | Sun X.,Fourth Peoples Hospital of Shenyang | Zhang J.,Shenyang University
Molecular Medicine Reports | Year: 2013

N-methyl-D-aspartate receptor subunit 1 (NMDAR1) and cAMP response element binding protein (CREB) play a role in vision plasticity. However, the correlation between their expression and vision plasticity is not clear. The present study aimed to examine the expression of NMDAR1 and phosphorylated CREB (pCREB) in the visual cortex of monocularly-deprived (MD) rats in the developmental phase. Eighty healthy Sprague Dawley rats were randomly divided into 4 groups (n=20); normal, MD, KN-93 (MD rats treated with KN-93, a calmodulin kinase IV inhibitor) and saline (MD rats treated with saline as control). All rats were reared for 45 days in a naturally lit environment. The expression of NMDAR1 and pCREB in the hibateral visual cortex of rats from each group was detected by immunohistochemistry and western blot analysis. The results demonstrate that, compared with the normal group, the expression of NMDAR1 and pCREB was increased in deprived and decreased in the non-deprived-side visual cortex in MD. Compared with the saline group, no significant difference was identified in NMDAR1 expression while pCREB expression was decreased in the deprived-side visual cortex in KN-93. No significant difference in the expression of NMDAR1 and pCREB in the non-deprived-side visual cortex between the KN-93 and saline groups was observed. The results indicate that NMDAR1 and CREB are involved in the ocular dominance forming process and play a role in vision plasticity. Copyright © 2013 Spandidos Publications Ltd.


Wang H.,Fourth Peoples Hospital of Shenyang | Wang H.,Shenyang University | Chen X.,Fourth Peoples Hospital of Shenyang
International Journal of Molecular Medicine | Year: 2013

The aim of the present study was to evaluate the effects of blocking the Rho kinase pathway on non-perfused regions and angiogenesis in the retina of rats using a rat model of oxygen-induced retinopathy (OIR) by observing the sequential expression of intercellular adhesion molecule-1 (ICAM-1), hypoxia-inducible factor-1 (HIF-1), B-cell lymphoma/leukemia-2 gene (Bcl-2) and caspase-3 mRNA following the administration of the Rho kinase inhibitor, fasudil (FSD). A total of 240 newborn rats were randomly divided into a normoxia control (N) group, a hyperoxia (H) group and a H + FSD (HF) group. The rats were sacrificed, and the eyes were enucleated from postnatal day (P)12 to P21. Samples were prepared for retinal flat mounts, mRNA and protein quantification. On P14, a higher number of circuitous retinal veins was observed in the H group compared with the HF group. In the HF group, the avascular area was significantly reduced compared with the H group on P18 (P>0.01). In the HF group, the mRNA expression of Bcl-2 was significantly increased on P15 compared with the N and H group (P>0.01). On P15 and P17 in the H group and on P13 in the HF group, the mRNA expression of ICAM-1 was significantly increased compared with the other groups (P>0.05). In the H and HF group, the expression of HIF-1a was significantly increased on P12 compared with the N group (P>0.05). On P19 and P21, HIF-1a expression was significantly increased to a maximum level in the HF group compared with the H and N group (P>0.01). In conclusion, these results suggest that FSD inhibits the expression of ICAM-1, assisting in the release of Bcl-2, suppressing caspase-3. In the HF group, the retinal flat mounts revealed that FSD had a vasorelaxant effect. On P18, a double-layered retinal vascular network was formed, and the number of non-perfused regions was significantly reduced. However, the late-phase peak expression of HIF-1a resulted in an inevitable increase in vascular endothelial growth factor expression and further accelerated neovascularization and vascular reconstruction in the immature retinal model.


Li L.-C.,Liaoning Blood Center | He Z.,Fourth Peoples Hospital of Shenyang | Li J.-P.,Liaoning Blood Center
Chinese Journal of Tissue Engineering Research | Year: 2013

BACKGROUND: Compared to bone marrow-, peripheral blood-, fat- and embryo-derived mesenchymal stem cells, umbilical cord- and placenta-derived mesenchymal stem cells possess advantages including wide source, ease of harvesting, no immunological rejection or ethical compromise.OBJECTIVE: To investigate the methods to in vitro isolate, culture and sub-culture of placenta-derived mesenchymal stem cells, providing experimental basis for clinical application of placenta-derived mesenchymal stem cells.PO. Box 1200, Shenyang 110004 www.CRTER.org. METHODS: A computer-based online retrieval was performed to search papers regarding placenta-derived mesenchymal stem cells published in PubMed database, Chinese Journal Full Text Database, Wanfang database using key words "placenta-derived mesenchymal stem cells, induction and differentiation in vitro". A total of 98 papers were retrieved, and 33 were suitable for final analysis.RESULTS AND CONCLUSION: Placenta-derived mesenchymal stem cells are in the stage of basic research in China, but some progress has been made in basic research and clinical application of placenta-derived mesenchymal stem cells in countries outside China. Placenta-derived mesenchymal stem cells possess advantages including wide source, ease in sample harvesting and no immunological rejection or ethical compromise as well as less pain, fewer infection opportunities and stronger proliferative capacity compared to bone marrow donation or peripheral blood collection. For these reasons, placenta-derived mesenchymal stem cells should be further studied.


Liu L.,Liaoning Medical University | Jiao J.,Shenyang Medical College | Wang Y.,Liaoning Medical University | Zhang D.,Fourth Peoples Hospital of Shenyang | And 2 more authors.
PLoS ONE | Year: 2014

Objective: The TP53BP1 gene may be involved in the development of cancer through disrupting DNA repair. However, studies investigating the relationship between TP53BP1 Glu353Asp (rs560191) polymorphism and cancer yielded contradictory and inconclusive outcomes. In order to realize these ambiguous findings, a meta-analysis was performed to assess the association between the TP53BP1 Glu353Asp (rs560191) polymorphism and susceptibility to cancer. Methods: We conducted a search of all English reports on studies for the association between the TP53BP1 Asp353Glu (rs560191) polymorphism and susceptibility to cancer using Medline, the Cochrane Library, EMbase, Web of Science, Google (scholar), and all Chinese reports were identified manually and on-line using CBMDisc, Chongqing VIP database, and CNKI database. The strict selection criteria and exclusion criteria were determined, and odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. The fixed or random effect model was selected based on the heterogeneity test among studies. Publication bias was estimated using funnel plots and Egger's regression test. Results: A total of seven studies were included in the meta-analysis including 3,213 cases and 3,849 controls. The results indicated that the Glu353Asp (rs560191) polymorphism in TP53BP1 gene had no association with cancer risk for all genetic models. In the subgroup analysis, the results suggested that Glu353Asp polymorphism was not associated with the risk of cancer according to ethnicity, cancer type, genotyping method, adjusted with control or not, HWE and quality score. Conclusions: This meta-analysis suggested that the Glu353Asp (rs560191) polymorphism in TP53BP1 gene was not associated with risk of cancer. Copyright: © 2014 Liu et al.


Zhang X.-Y.,Fourth Peoples Hospital of Shenyang | Guo X.-F.,Liaoning Medical University | Zhang S.-D.,Fourth Peoples Hospital of Shenyang | He J.-N.,Fourth Peoples Hospital of Shenyang | And 4 more authors.
International Journal of Ophthalmology | Year: 2014

AIM To compare the effectiveness and safety between bevacizumab and ranibizumab in the treatment of age-related macular degeneration (AMD) through a systematic review and meta-Analysis. METHODS We performed a comprehensive search of randomized controlled trials (RCTs), non-RCTs, case-control and cohort studies that compared bevacizumab and ranibizumab using PubMed and the Cochrane Library. After the related data were extracted by two investigators independently, pooled weighted mean differences (WMDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using a random-effects or a fixed-effects model. RESULTS A total of four RCTs involving 1927 patients and eleven retrospective case series involving 2296 patients were included. For the primary outcomes, no significant differences were found between ranibizumab group and bevacizumab group in visual acuity (WMD: -0.04; 95%CI: -0.08 to 0.00; P=o.o6), best corrected visual acuity (WMD: -0.05; 95%CI: -0.10 to 0.00; P=o.O5), retina thickness (WMD: -4.69; 95%CI: -13.15 to 3.7 6; P=o.86) and foveal thickness (WMD: 10.91; 95%CI: -14.73 to 36.56; ^=0.40). The pooled analyses in the evaluation of safety showed that compared to bevacizumab, ranibizumab was associated with decreased risks of ocular inflammation (RR: 0.45; 95% CI: 0.23 to 0.89; P=o.O2) and venous thrombotic events (RR: 0.27; 95%CI: 0.08 to 0.89; P=o.O3). However, there were no significant differences observed in deaths (^=0.69) and arterial thromboembolic events (P=o.7 1) between the two groups. CONCLUSION With equal clinical efficacy, ranibizumab was found to be associated with less adverse events compared to bevacizumab, indicating that ranibizumab might be a safer management. © International Journal of Ophthalmology Press.


Chen P.,Fourth Peoples Hospital Of Shenyang | Wang J.,Liaoning Medical University
Chinese Journal of Tissue Engineering Research | Year: 2015

BACKGROUND: Lung cancer stem cells are tightly related to the treatment and prognosis of lung cancer. We can provide more references for clinical diagnosis and treatment of lung cancer through the study on the tumorigenicity and surface markers of lung cancer stem cells. OBJECTIVE: To explore the enrichment methods for lung cancer stem cells and cellular tumorigenicity. METHODS: Lung cancer stem cells were induced in serum-free culture medium containing epidermal growth factor, insulin-like growth factor 1, and basic fibroblast growth factor. Then, the expressions of related surface markers were detected using immunofluorescence method. After that, mice were implanted subcutaneous with lung cancer stem cell spheres to understand the tumorigenicity of lung cancer stem cells. RESULTS AND CONCLUSION: Lung cancer stem cells under serum-free induction and culture were changed to sphere-forming cells, and the immunofluorescence detection showed that over 80% of sphere-forming cells were positive for CCSP, SP-C and OCT4. After transplantation of sphere-forming cells, the mice showed a high tumorigenicity. These findings indicate that sphere-forming cells are formed after serum-free suspension culture of lung cancer stem cells, which have a higher tumorigenicity. © 2015, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.

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