Yixiong Zhou

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.

Microarray-based analysis: identification of hypoxia-regulated microRNAs in retinoblastoma cells.

Hypoxia is an essential feature of retinoblastoma and contributes to poor prognosis and resistance to conventional therapy. MicroRNAs (miRNAs) are small non-coding RNAs involved in a wide variety of biological processes, including cell differentiation, proliferation, death and metabolism. However, the relationship between hypoxia and the expression of miRNAs in retinoblastoma is not well understood. In this study, we aimed to analyze the pattern of miRNA expression in a retinoblastoma cell line under hypoxic conditions and to identify the miRNAs regulated by hypoxia, as well as their possible functions. miRNA expression profiling in retinoblastoma cells (HXO-RB44) under normal and hypoxic conditions was assessed by microarray techniques. The differentially expressed miRNAs were subjected to bioinformatic analyses to predict and categorise the key miRNAs and their target genes. A quantitative real-time RT-PCR approach was used to validate their expression. A Cell Counting kit was used to evaluate the functional significance of miR-181b in RB cell proliferation. There were 46 miRNAs that changed expression more than 2-fold in response to hypoxia (34 up-regulated and 12 down-regulated). We identified a cluster of miRNAs that includes miR-181b, miR-125a-3p, miR-30c-2, miR-497 and miR-491-3p as hypoxia-regulated miRNAs (HRMs) in retinoblastoma cells, of which miR-181b was the most typically differentially expressed miRNA under hypoxic conditions. Functionally, these HRMs are involved in apoptosis, cell adhesion, cell proliferation and mRNA processing, all processes that associate closely with the hypoxia response of cancer cells. Additionally, we found that administration of miR-181b inhibitor can suppress proliferation of retinoblastoma cells. These findings provide the first evidence that miRNAs play an important role in the hypoxia response of retinoblastoma cells. MiR-181b, the most typically up-regulated miRNA may aid in future clinical intervention of retinoblastoma.

Evaluation of the optimum solute concentration for good glass forming ability in multicomponent metallic glasses

Abstract Previous work suggests that the size factor may be the most crucial one on the glass forming ability (GFA). But the alloys in a system have significant deference for GFA. A criterion λ n is defined in the present work to comprehensively evaluate concentration dependence of GFA of alloys in a system. It is found that the values of λ n of bulk glass formers with greatest GFA in Zr-, Pd-, Mg-, Nd- and Fe-based systems are nearly constant of 0.18. Based on the mathematical description of regular polytopes and the dense random packing of hard sphere (DRPHS) model, a cluster model is suggested. This model provides the physical meaningful origin of the λ n from the view of free volume. The glass structure of bulk glass formers with λ n ≈0.18 has optimum defect concentration within the framework of the cluster model. In the term of λ n criterion, an alloy with λ n of about 0.18 will be one of bulk glass former candidates, which is verified by the experimental result of ZrAlNi system.

Wigner–Ville distribution based on cyclic spectral density and the application in rolling element bearings diagnosis

The vibration signals of rolling element bearings are random cyclostationary when they have faults. Also, statistical properties of the signals change periodically with time. The accurate analysis of time-varying signals is an essential pre-requisite for the fault diagnosis and hence safe operation of rolling element bearings. The Wigner distribution is probably most widely used among the Cohen’s class in order to describe how the spectral content of a signal changes over time. However, the basic nature of such signals causes significant interfering cross-terms, which do not permit a straightforward interpretation of the energy distribution. To overcome this difficulty, the Wigner–Ville distribution (WVD) based on the cyclic spectral density (CSD) is discussed in this article. It is shown that the improved WVD, based on CSD of a long time series, can render the time–frequency distribution less susceptible to noise, and restrain the cross-terms in the time–frequency domain. Simulation and experiment of the rolling element-bearing fault diagnosis are performed, and the results indicate the validity of WVD based on CSD in time–frequency analysis for bearing fault detection.

Inhibition of retinoblastoma in vitro and in vivo with conditionally replicating oncolytic adenovirus H101.

PURPOSE To determine the therapeutic effect of oncolytic adenovirus H101 on retinoblastoma in vitro and in vivo. METHODS The expression of coxsackievirus-adenovirus receptor (CAR) in human retinoblastoma cell line HXO-RB(44) was determined by RT-PCR, Western blot, immunofluorescence, and immunocytochemistry staining. Appropriate multiplicity of infection was determined using flow cytometry in retinoblastoma cells with green fluorescent protein-expressing adenovirus (AdGFP). The viability of HXO-RB(44) cells treated with H101 or AdGFP was measured using a cell counting kit-8-based procedure. Viral proliferation in vitro was measured by end point dilution titration and real-time PCR. Cell cycle and apoptotic activity of HXO-RB(44) were analyzed by flow cytometry. NOD-SCID mice bearing retinoblastoma xenografts were treated with intratumoral injection of H101, AdGFP, or PBS. Tumor volume and survival time were recorded. Immunohistochemistry for adenoviral fiber protein and Western blot for adenoviral Hexon protein of retinoblastoma xenografts were performed to evaluate H101 virus replication in vivo. RESULTS HXO-RB(44) cells expressed CAR and were sensitive to adenoviral infection. HXO-RB(44) cells treated with H101 had reduced cell viability compared with AdGFP-treated cells (P < 0.01). Abundant replication of H101 in HXO-RB(44) cells resulted in G(2)/M-phase arrest and finally tumor cell lysis, but the apoptosis pathway was not activated. Tumor-bearing mice treated with H101 had reduced tumor burdens and prolonged survival times compared with PBS and AdGFP controls (both P < 0.01). Immunohistochemical and Western blot examination revealed widespread replication of H101 within the tumor. CONCLUSIONS These results suggest that H101 effectively inhibits the growth of retinoblastoma cells in vitro and in mice and may serve as a novel therapy for retinoblastoma.

Potentiation of tumor radiotherapy by a radiation-inducible oncolytic and oncoapoptotic adenovirus in cervical cancer xenografts

The p53 tumor suppressor pathway is impaired in more than 90% of cervical cancers and cancer‐derived cell lines as a result of infection by human papillomavirus (HPV). The HPV E6 oncoprotein forms complexes with p53 and promotes its degradation via ubiquitin‐dependent mechanism. In our study, we attempted to improve the clinical outcomes of this combined therapy by modifying the p53‐targeted adenovirus to become radiation‐responsive. The antitumor adenovirus was constructed by inserting a radiation‐responsive expression cassette composed of the promoter of early growth response‐1 (Egr‐1) and the proapoptotic protein TRAIL. We showed that the addition of adenovirus containing Egr‐1/TRAIL significantly increased cell death and apoptosis caused by radiotherapy. In mice bearing xenograft tumors, intratumoral administration of the Egr‐1/TRAIL adenovirus followed by radiation significantly reduced tumor growth and enhanced tumor survival. Our Egr‐1/TRAIL adenoviral gene product may offer a novel “one‐two punch” tumor therapy for cervical cancers not only by potentiating radiation treatment but also by preserving p53 defect‐specific tumor killing of the oncolytic adenovirus.

Recombinant oncolytic adenovirus H101 combined with siBCL2: cytotoxic effect on uveal melanoma cell lines

Background Deregulation of Bcl2 pathway is implicated in the pathogenesis of uveal melanoma (UM). Oncolytic adenovirus H101 is the worlds first oncolytic viral therapy for cancer approved for clinical use. We aimed to explore a potential synergy of downregulating Bcl2 pathway using a small interfering RNA (siBCL2) combined with H101 therapy on UM cell lines. Methods The sensitivity to adenovirus infection was analysed by flow cytometry. PCR, real-time-PCR and western blot were used to detect Bcl2, p53, Bax and fibre expression. Appropriate multiplicity of H101 infection and cell survival rate were measured by a cell counting kit-8 assay. UM cells were stained with Annexin-V and propidium iodide for apoptosis assay and cell cycle distribution. Results VUP cells (without elevation of Bcl2) exhibited greater sensitivity to adenovirus infection than OM431 cells (Bcl2 elevated cell line). Bcl2 expression was markedly reduced by siBCL2 or siBCL2 plus H101. Combined treatment with siBCL2 and H101 produced substantial growth inhibition of OM431 cells by enhancing apoptosis and cell cycle arrest through Bax-p53-induced apoptotic pathway. Conclusions SiBCL2 and H101 exhibited synergistic cytotoxic effect in Bcl2 elevated UM cell lines and could potentially serve as a novel targeted molecular therapy for UM.

Radiation‐inducible human tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) gene therapy: a novel treatment for radioresistant uveal melanoma

Uveal melanoma (UM) is one of the most therapy‐resistant cancers. Radiotherapy is the preferred treatment for most cases of UM. However, some UM cells, such as the SP6.5 or OM431 cell lines, are relatively radioresistant. In this study, we attempted to improve the current UM therapy using an adenovirus radio‐inducible gene therapy system. The antitumor adenovirus was constructed by inclusion of the radiation‐inducible early growth response gene 1 (EGR1) promoter and the anticancer tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) gene. We demonstrated that the UM SP6.5 and OM431 cell lines were susceptible to the TRAIL‐induced antitumor effect. TRAIL expression was enhanced in the adenovirus containing EGR1/TRAIL (Ad‐ET) treatment group by radiotherapy, whereas Ad‐ET significantly increased cell death and apoptosis caused by radiotherapy. In mice bearing xenograft tumors, apoptotic cells were detected in pathological tumor sections. Adenovirus Ad‐ET combined with radiation therapy significantly inhibited tumor growth compared with the other treatment groups (P < 0.01). Our findings indicate that radioresponsive gene therapy has the potential to be a more effective and specific therapy for UM because the therapeutic gene can be spatially or temporally controlled by exogenous radiation.

Functional significance of B7-H1 expressed by human uveal melanoma cells

B7-H1, a recently described B7 family member, has been reported to negatively regulate T-cell function in most cancer cells. In this study, we sought to investigate B7-H1 expression in four uveal melanoma (UM) cells (OCM1, SP6.5, OM431 and VUP) to determine the functional significance of B7-H1 expression in T-cell immune response. Using flow cytometry (FCM), we demonstrated that SP6.5 cells had high B7-H1 protein expression, while the other three UM cell lines had none. However, all four UM cell lines expressed B7-H1 mRNA, as confirmed by reverse transcription-polymerase chain reaction. In co-culture experiments using B7-H1-expressing UM cells with T-cells, FCM to determine CD69 expression in T-cells revealed that SP6.5 cell-related B7-H1 inhibited T-cell activation. This effect was eliminated by B7-H1-targeted RNA interference. An Annexin V/PI double staining assay further showed that B7-H1 expressed by SP6.5 cells did not increase the apoptosis of T-cells, though it was found in a variety of other solid tumors. In conclusion, all the UM cell lines constitutively expressed B7-H1 mRNA, while B7-H1 protein was expressed at different levels. UM-related B7-H1 expression negatively regulated T-cell immune response through the inhibition of T-cell activation, and not through the promotion of T-cell apoptosis. This provides new insight into anti-tumor immunity against B7-H1-expressing UM cells.

The relation between formation of compounds and glass forming ability for Zr–Al–Ni alloys

Abstract This paper reports the formation of compounds during the solidification process of liquid Zr 85− x Al 15 Ni x ( x =15, 20, 25, 30, 35) alloys studied by X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). The results indicate that compound AlNi 4 Zr 5 forms when liquid alloys containing 20, 25 and 30 at.% nickel solidify. It is suggested in this work that the large glass forming ability (GFA) of the Zr–Al–Ni system is attributed to the difficulty of formation of compound AlNi 4 Zr 5 as a primary phase during solidification process of liquid alloys. In comparing the phases appearing in the solidification structure of the liquid Zr 60 Al 15 Ni 25 alloy with the products formed during crystallization process of this amorphous alloy, it is assumed that Al 2 NiZr 6 is a metastable phase, which decomposes into equilibrium phases during the subsequent cooling process.