Xianqun Fan

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.

Putative tumor suppressor miR-145 inhibits colon cancer cell growth by targeting oncogene friend leukemia virus integration 1 gene

Tumor suppressor microRNA miR‐145 is commonly down‐regulated in colon carcinoma tissues, but its specific role in tumors remains unknown.

Intrachromosomal Looping Is Required for Activation of Endogenous Pluripotency Genes during Reprogramming

Generation of induced pluripotent stem cells (iPSCs) by defined factors is an extremely inefficient process, because there is a strong epigenetic block preventing cells from achieving pluripotency. Here we report that virally expressed factors bound to the promoters of their target genes to the same extent in both iPSCs and unreprogrammed cells (URCs). However, expression of endogenous pluripotentcy genes was observed only in iPSCs. Comparison of local chromatin structure of the OCT4 locus revealed that there was a cohesin-complex-mediated intrachromosomal loop that juxtaposes a downstream enhancer to the genes promoter, enabling activation of endogenous stemness genes. None of these long-range interactions were observed in URCs. Knockdown of the cohesin-complex gene SMC1 by RNAi abolished the intrachromosomal interaction and affected pluripotency. These findings highlight the importance of the SMC1-orchestrated intrachromosomal loop as a critical epigenetic barrier to the induction of pluripotency.

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.

Long noncoding RNA-mediated intrachromosomal interactions promote imprinting at the Kcnq1 locus

A long noncoding RNA directly builds an intrachromosomal interaction complex to establish allele-specific transcriptional gene silencing over a large chromosomal domain.

Bone marrow stromal cells with a combined expression of BMP-2 and VEGF-165 enhanced bone regeneration*

Bone graft substitutes with osteogenic factors alone often exhibit poor bone regeneration due to inadequate vascularization. Combined delivery of osteogenic and angiogenic factors from biodegradable scaffolds may enhance bone regeneration. We evaluated the effects of bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF), combined with natural coral scaffolds, on the repair of critical-sized bone defects in rabbit orbits. In vitro expanded rabbit bone marrow stromal cells (BMSCs) were transfected with human BMP2 and VEGF165 genes. Target protein expression and osteogenic differentiation were confirmed after gene transduction. Rabbit orbital defects were treated with a coral scaffold loaded with BMP2-transduced and VEGF-transduced BMSCs, BMP2-expressing BMSCs, VEGF-expressing BMSCs, or BMSCs without gene transduction. Volume and density of regenerated bone were determined by micro-computed tomography at 4, 8, and 16 weeks after implantation. Neovascularity, new bone deposition rate, and new bone formation were measured by immunostaining, tetracycline and calcein labelling, and histomorphometric analysis at different time points. The results showed that VEGF increased blood vessel formation relative to groups without VEGF. Combined delivery of BMP2 and VEGF increased new bone deposition and formation, compared with any single factor. These findings indicate that mimicking the natural bone development process by combined BMP2 and VEGF delivery improves healing of critical-sized orbital defects in rabbits.

Recent advances in bioprinting techniques: approaches, applications and future prospects.

Bioprinting technology shows potential in tissue engineering for the fabrication of scaffolds, cells, tissues and organs reproducibly and with high accuracy. Bioprinting technologies are mainly divided into three categories, inkjet-based bioprinting, pressure-assisted bioprinting and laser-assisted bioprinting, based on their underlying printing principles. These various printing technologies have their advantages and limitations. Bioprinting utilizes biomaterials, cells or cell factors as a “bioink” to fabricate prospective tissue structures. Biomaterial parameters such as biocompatibility, cell viability and the cellular microenvironment strongly influence the printed product. Various printing technologies have been investigated, and great progress has been made in printing various types of tissue, including vasculature, heart, bone, cartilage, skin and liver. This review introduces basic principles and key aspects of some frequently used printing technologies. We focus on recent advances in three-dimensional printing applications, current challenges and future directions.

Electrospun chitosan-graft-poly (ɛ-caprolactone)/poly (ɛ-caprolactone) nanofibrous scaffolds for retinal tissue engineering.

A promising therapy for retinal diseases is to employ biodegradable scaffolds to deliver retinal progenitor cells (RPCs) for repairing damaged or diseased retinal tissue. In the present study, cationic chitosan-graft-poly(ɛ-caprolactone)/polycaprolactone (CS-PCL/PCL) hybrid scaffolds were successfully prepared by electrospinning. Characterization of the obtained nanofibrous scaffolds indicated that zeta-potential, fiber diameter, and the content of amino groups on their surface were closely correlated with the amount of CS-PCL in CS-PCL/PCL scaffolds. To assess the cell–scaffold interaction, mice RPCs (mRPCs) were cultured on the electrospun scaffolds for 7 days. In-vitro proliferation assays revealed that mRPCs proliferated faster on the CS-PCL/PCL (20/80) scaffolds than the other electrospun scaffolds. Scanning electron microscopy and the real-time quantitative polymerase chain reaction results showed that mRPCs grown on CS-PCL/PCL (20/80) scaffolds were more likely to differentiate towards retinal neurons than those on PCL scaffolds. Taken together, these results suggest that CS-PCL/PCL(20/80) scaffolds have potential application in retinal tissue engineering.

Long non-coding RNA ROR decoys gene- specific histone methylation to promote tumorigenesis

Long non-coding RNAs (lncRNAs) are not translated into proteins and were initially considered to be part of the ‘dark matter’ of the genome. Recently, it has been shown that lncRNAs play a role in the recruitment of chromatin modifying complexes and can influence gene expression. However, it is unknown if lncRNAs function in a similar way in cancer. Here, we show that the lncRNA ROR occupies and activates the TESC promoter by repelling the histone G9A methyltransferase and promoting the release of histone H3K9 methylation. Suppression of ROR in tumors results in silencing of TESC expression, and G9A-mediated histone H3K9 methylation in the TESC promoter is restored, which significantly reduces tumor growth and metastasis. Without ROR silencing, TESC knockdown presents consistent and significant reductions in tumor progression. Our results reveal a novel mechanism by which ROR may serve as a decoy oncoRNA that blocks binding surfaces, preventing the recruitment of histone modifying enzymes, thereby specifying a new pattern of histone modifications that promote tumorigenesis.BackgroundLong non-coding RNAs (lncRNAs) are not translated into proteins and were initially considered to be part of the ‘dark matter’ of the genome. Recently, it has been shown that lncRNAs play a role in the recruitment of chromatin modifying complexes and can influence gene expression. However, it is unknown if lncRNAs function in a similar way in cancer.ResultsHere, we show that the lncRNA ROR occupies and activates the TESC promoter by repelling the histone G9A methyltransferase and promoting the release of histone H3K9 methylation. Suppression of ROR in tumors results in silencing of TESC expression, and G9A-mediated histone H3K9 methylation in the TESC promoter is restored, which significantly reduces tumor growth and metastasis. Without ROR silencing, TESC knockdown presents consistent and significant reductions in tumor progression.ConclusionsOur results reveal a novel mechanism by which ROR may serve as a decoy oncoRNA that blocks binding surfaces, preventing the recruitment of histone modifying enzymes, thereby specifying a new pattern of histone modifications that promote tumorigenesis.

Late reconstruction of the complex orbital fractures with computer-aided design and computer-aided manufacturing technique.

Background: To construct three-dimensional (3D) imaging and computer generated models of complex orbital fractures, and develop a Computer-Aided Design/Computer-Aided Manufacture (CAD/CAM) system to help improve the surgical planning of complex orbital fracture and promote its outcome. Methods: A prospective study was carried out on 17 patients with unilateral complex orbital fractures from Mar 2003 to Mar 2006 at the Shanghai ninth peoples hospital. The utilization of a CAD/CAM technique based on Helical computer tomography data, with stereolithographical (SLA) modelling as intermediate step, enabled surgeons to plan for the surgical progress of osteotomy, movement, reposition, fixation and material implanting. Orbital volume was calculated pre and post-operatively. Orbital fracture reconstruction and globe repositioning was performed and followed up 3-9 months post-treatment. Ocular function and aesthetic deformities such as enophthalmos, diplopia and extraocular motility problems were accessed. The data was processed with SAS 6.17 statistical software. Results: 17 patients with complex orbital fractures underwent successful orbital fracture reconstruction surgery. The deformities of orbit, medial canthus, nose, zygomata, maxillary and frontal bone were well corrected. The volume of reconstructed orbit was approximately symmetrical with respect to the contralateral orbit. Enophthalmos was corrected and diplopia, extraocular movement were improved. Conclusions: CAD/CAM system enables the surgeon to predict reconstructive surgical steps before the operation, and can help to improve the outcome of surgery. This technique may be proved as one of the most useful clinical tools for orbital surgery.