Yefei Wang

High prevalence of myopia and high myopia in 5060 Chinese university students in Shanghai.

PURPOSE Myopia is an important cause of correctable visual impairment worldwide. Genetic and environmental factors contribute to its development. The population of Chinese university students consists of approximately 30 million young people characterized by academic excellence and similar ages. To date, little is known about their refractive status. Our study is designed to investigate the prevalence of myopia in this specific population. METHODS This is a cross-sectional study of myopia among university students in Shanghai, China; 5083 students from Donghua University were enrolled. All participants first responded to a detailed questionnaire, including questions on ethnicity, birth date, and family history, and then undertook a standardized ophthalmologic examination, including visual acuity, a slit-lamp examination, and non-cycloplegic autorefraction. RESULTS The mean spherical equivalent refraction (SER) of the university students was -4.1 diopters (D). Of the subjects 95.5% were myopic (SER < -0.50 D), 19.5% were highly myopic (SER < -6.0 D), and only 3.3% were emmetropic (-0.5 D ≤ SER ≤ 0.5 D). The postgraduates were more myopic than the undergraduates (96.9% and 94.9%, respectively). Being female (-4.1 ± 2.4 D in female versus -3.8 ± 2.4 D in male subjects), of Han ethnicity (-4.1 ± 2.4 D in Han versus -3.4 ± 2.2 D in minorities), and of older age were associated with a higher probability of myopia only in the undergraduate population. CONCLUSIONS The prevalence of myopia and high myopia in this university student population was high. The refractive status of this population deserves further attention.

Effects of a miR-31, Runx2, and Satb2 Regulatory Loop on the Osteogenic Differentiation of Bone Mesenchymal Stem Cells

Recently, a cohort of miRNAs, including miR-31, was reported to be downregulated during osteogenic induction by miR microarray analysis. It remains unclear how changes in miR-31 expression collaborate with bone transcription factors to activate the biological pathways that regulate the differentiation of bone mesenchymal stem cells (BMSCs). Here the effects of miR-31, Runx2, and Satb2 on the osteogenic differentiation of BMSCs were investigated using mimics and inhibitors of miR-31, small interfering RNA for knockdown of Runx2 and plasmids for overexpression of Runx2. Our results showed that miR-31 expression decreased progressively in BMSC cultures during differentiation. Inhibition of miR-31 dramatically increased the alkaline phosphatase activity and mineralization in BMSC cultures. Additionally, miR-31 diminished the levels of the Satb2 protein without significantly affecting Satb2 mRNA levels, and Runx2 directly repressed miR-31 expression. Overexpression of miR-31 significantly reduced expression of the osteogenic transcription factors OPN, BSP, OSX, and OCN, but not Runx2. Furthermore, the high expression of miR-31 in BMSCs cultured in the proliferation medium repressed Satb2 protein levels, which may contribute to the maintenance of BMSCs in an undifferentiated state. In conclusion, our results suggest that a Runx2, Satb2, and miR-31 regulatory mechanism may play an important role in inducing BMSC osteogenic differentiation. The results of this study provide us with a better understanding of the molecular mechanisms that govern the BMSC fate.

Effects of miR-31 on the osteogenesis of human mesenchymal stem cells.

Exploring the molecular mechanisms that regulate the osteogenesis of human mesenchymal stem cells (hMSCs) will bring us more efficient methods for improving the treatment of bone-related diseases. In this study, we analyzed the effects of miR-31 on the osteogenesis of hMSCs. The overexpression of miR-31 repressed the osteogenesis of hMSCs, whereas the downregulation enhanced this process. SATB2 was testified to be a direct target of miR-31, and its effects on the osteogenesis were also described. Most importantly, the knockdown of SATB2 attenuated miR-31s osteogenic effects. Taken together, our findings suggest that miR-31 regulates the osteogenesis of hMSCs by targeting SATB2.

Insulin-like growth factor 1 promotes the proliferation and adipogenesis of orbital adipose-derived stromal cells in thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) is characterised by increased volume of the orbital contents involving adipose tissue, but the factors responsible for stimulation of orbital adipogenesis remain uncertain. Previous studies have shown that insulin-like growth factor 1 (IGF-1) is increased in the orbital fatty connective tissues of patients with TAO. The present study was conducted to investigate the effects of IGF-1 on orbital adipose-derived stromal cells (OADSCs) derived from TAO patients and to identify the signalling mechanisms involved. Our results showed that IGF-1 significantly promoted the cell proliferation and lipid accumulation of TAO OADSCs. The mRNA expression of adipogenic markers (adiponectin, leptin, adipocyte fatty acid binding protein [AP2] and fatty acid synthase [FAS]) was increased in TAO cultures treated with IGF-1. Further research demonstrated that the protein levels of peroxisome proliferator-activated receptor-γ (PPARγ) were up-regulated when OADSCs were treated with IGF-1. We also found that the inhibition of either IGF-1 receptor (IGF-1R) or phosphoinositide 3-kinase (PI3K) activity decreased the levels of IGF-1-stimulated mRNA encoding adiponectin, leptin, AP2, and FAS, as well as PPARγ protein levels. Moreover, the expression of phosphorylated Akt (p-Akt) protein in TAO cells was up-regulated by IGF-1, while a specific PI3K inhibitor (LY294002) or an antibody of IGF-1R blocked this effect. These results indicate that IGF-1 is a pro-proliferative and pro-adipogenic factor in TAO OADSCs. IGF-1 enhances the adipogenesis of TAO OADSCs by up-regulation of PPARγ via the activation of the IGF-1R and PI3K pathways, suggesting that the blocking of IGF-1R or inhibition of PI3K signalling might be a potential novel therapeutic approach to TAO.

Characterization of human ethmoid sinus mucosa derived mesenchymal stem cells (hESMSCs) and the application of hESMSCs cell sheets in bone regeneration

Mesenchymal stem cells (MSCs) have been extensively applied in the field of tissue regeneration. MSCs derived from various tissues exhibit different characteristics. In this study, a cluster of cells were isolated from human ethmoid sinus mucosa membrane and termed as hESMSCs. hESMSCs was demonstrated to have MSC-specific characteristics of self-renewal and tri-lineage differentiation. In particular, hESMSCs displayed strong osteogenic differentiation potential, and also remarkably promoted the proliferation and osteogenesis of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Next, hESMSCs were prepared into a cell sheet and combined with a PSeD scaffold seeded with rBMSCs to repair critical-sized calvarial defects in rats, which showed excellent reparative effects. Additionally, ELISA assays revealed that secreted cytokines, such as BMP-2, BMP-4 and bFGF, were higher in the hESMSCs conditioned medium, and immunohistochemistry validated that hESMSCs cell sheet promoted the expression of BMP signaling downstream genes in newly formed bone. In conclusion, hESMSCs were demonstrated to be a class of mesenchymal stem cells that possessed high self-renewal capacity along with strong osteogenic potential, and the cell sheet of hESMSCs could remarkably promote new bone regeneration, indicating that hESMSCs cell sheet could serve as a novel and promising alternative strategy in the management of bone regeneration.

In Vivo Efficacy of Bone Marrow Stromal Cells Coated with Beta-Tricalcium Phosphate for the Reconstruction of Orbital Defects in Canines

PURPOSE To repair the segmental orbital rim defects of dogs with three-dimensional (3D) tissue-engineered constructs derived from culturing autogenous bone marrow stromal cells (BMSCs) on β-tricalcium phosphate (β-TCP) scaffolds. METHODS A 25-mm segmental defect on the canine inferior orbital rim was created. BMSCs were isolated and osteogenically induced in vitro, then were seeded onto 3D β-TCP scaffolds and implanted to repair the orbital defects after 5 days of cultivation. The group of noninduced BMSC/β-TCP, β-TCP alone, and the normal inferior orbital rim were set as controls. The orbits of all groups had spiral computed tomography (CT) scans 1, 4, 8, and 12 weeks after surgery. Gross examination, bone density, microCT, and histologic measurements were performed 12 weeks after surgery. The results were analyzed to evaluate the extent of bone repair. RESULTS Twelve weeks after surgery, CT examination revealed good inferior orbital rim recovery in the induced BMSC/β-TCP group, and the bone density was 0.30 ± 0.03 g/cm(2) with no dominant variance, compared with the normal control (P > 0.05). MicroCT and histologic examination confirmed that the implantations led to good repair of the defects. Pore-like spongy bone surrounded the implants through the section plane, with some residue remaining in the center. In contrast, the noninduced BMSC/β-TCP implants were not fully repaired, and nonunion was evident. The bony density for this group was 0.23 ± 0.07 g/cm(2), which was significantly lower than that of the control group (P < 0.05). The β-TCP group was largely held by fibrous tissues. CONCLUSIONS Engineered bone from induced BMSCs and 3D biodegradable β-TCP can efficiently repair critical-sized segmental orbital defects in dogs.

FOXL2 mutations in Chinese families with Blepharophimosis syndrome (BPES)

Blepharophimosis syndrome (BPES) is a rare, autosomal dominant disease. Two clinical types of BPES have been distinguished. In BPES type I, an eyelid malformation is associated with infertility in affected females as a result of premature ovarian failure. In BPES type II, eyelid anomalies alone are observed. Mutations of FOXL2, which is a gene encoding a forkhead transcription factor, have recently been shown to cause both types of BPES. Here, we report 1 novel duplication mutation of the FOXL2 gene identified in a large Chinese family affected by type II BPES and 1 less recurrent 17-bp duplication in a large Chinese family affected by BPES of an undetermined type. These new cases give additional support to the previously reported genotype-phenotype correlations and our findings have expanded the spectrum of known mutations of the FOXL2 gene.

In vitro osteogenic induction of bone marrow stromal cells with encapsulated gene-modified bone marrow stromal cells and in vivo implantation for orbital bone repair.

Osteogenic induction with either growth factors or genetic modification has limitations due to the short half-life and cost of the former, or safety concerns regarding the latter. The objective of this study was to employ a microcapsulation technique to separate genetically modified and nonmodified bone marrow stromal cells (BMSCs) to establish a cost-effective and biosafe osteogenic induction methodology with functional evaluation in vitro and in vivo in a canine model. Autologous BMSCs were isolated and transduced with adenoviral vectors containing either BMP-2 or vascular endothelial growth factor (VEGF) or were dual transduced followed by encapsulation in alginate microcapsules using an electrostatic bead generator. After cocultured with encapsulated cells, normal autologous BMSCs were analyzed for osteogenic differentiation and seeded onto tricalcium phosphate (TCP) scaffolds for in vivo implantation to repair orbital wall bone defects (12 mm in diameter) in a canine model. In vitro assays showed that the expression of the transduced genes was significantly upregulated, with significantly more transduced proteins released from the transduced cells compared with control cells. Importantly, examination of the BMSCs induced by soluble factors released from the encapsulated cells revealed a significant upregulation of expression of osteogenic markers Runx2, BSP, OPN, and OCN in dual-transduction or induction groups. In addition, dual transduction and induction resulted in the highest increase of alkaline phosphatase activity and mineralization compared with other experimental groups. In vivo assays using CT, micro-CT, and histology further supported the qPCR and western blot findings. In conclusion, encapsulation of genetically modified BMSCs was able to release a sufficient amount of BMP-2 and VEGF, which effectively induced osteogenic differentiation of normal-cultured BMSCs and demonstrated bone repair of the orbital wall defect after implantation with β-TCP in vivo.

A regulatory loop containing miR-26a, GSK3β and C/EBPα regulates the osteogenesis of human adipose-derived mesenchymal stem cells

Elucidating the molecular mechanisms responsible for osteogenesis of human adipose-derived mesenchymal stem cells (hADSCs) will provide deeper insights into the regulatory mechanisms of this process and help develop more efficient methods for cell-based therapies. In this study, we analysed the role of miR-26a in the regulation of hADSC osteogenesis. The endogenous expression of miR-26a increased during the osteogenic differentiation. The overexpression of miR-26a promoted hADSC osteogenesis, whereas osteogenesis was repressed by miR-26a knockdown. Additionally, miR-26a directly targeted the 3′UTR of the GSK3β, suppressing the expression of GSK3β protein. Similar to the effect of overexpressing miR-26a, the knockdown of GSK3β promoted osteogenic differentiation, whereas GSK3β overexpression inhibited this process, suggesting that GSK3β acted as a negative regulator of hADSC osteogenesis. Furthermore, GSK3β influences Wnt signalling pathway by regulating β-catenin, and subsequently altered the expression of its downstream target C/EBPα. In turn, C/EBPα transcriptionally regulated the expression of miR-26a by physically binding to the CTDSPL promoter region. Taken together, our data identified a novel feedback regulatory circuitry composed of miR-26a, GSK3β and C/EBPα, the function of which might contribute to the regulation of hADSC osteogenesis. Our findings provided new insights into the function of miR-26a and the mechanisms underlying osteogenesis of hADSCs.

Ocular Complications of Human Immunodeficiency Virus Infection in Eastern China

PURPOSE To investigate ocular complications in patients with HIV/AIDS in eastern China during the time of highly active antiretroviral therapy (HAART). DESIGN Prospective study. METHODS This study was carried out from August 1, 2009 to July 31, 2010. Recruited HIV/AIDS patients underwent a series of surveys and ophthalmologic and laboratory examinations (including CD4 level) at enrollment. RESULTS In this study, all 787 HIV/AIDS patients (1574 eyes) had a history of HAART. Of these patients, 28.72% (95% CI = 0.26-0.32) had a history of systemic disease and 26.30% (95% CI = 0.23-0.29) had ocular complications. Of these ocular complications, cytomegalovirus retinitis (CMVR) had the highest prevalence (10.6%, 83/787) and ocular microangiopathy had the second-highest prevalence (9.4%, 74/787). Among the patients with CMVR, 16.9% (14/83) suffered from immune recovery uveitis (IRU). Furthermore, 3.4% (27/787) of the recruited AIDS patients had neuro-ophthalmologic disorders. The mean logMAR visual acuity of the group with ocular complications was 0.47 ± 0.64, which was significantly different from the asymptomatic group (0.17 ± 0.39, P < .001). The median CD4 T-cell count of the group with ocular complications is 43 cells/μL, which was significantly different from the asymptomatic group (116.5 cells/μL, P < .001). CONCLUSIONS The study shows a high rate of treatable ocular complications among patients with HIV/AIDS in eastern China. HIV/AIDS treatment programs in China must be prepared to identify ocular complications and refer patients to the correct treatment facilities.