Establishment of OPG Transgenic Mice and the Effect of OPG on Bone Microarchitecture

Osteoprotegerin (OPG) plays a determinant role in regulating bone metabolism, but the effect of OPG on bone microarchitecture needs to be further elucidated. We attempted to construct pCI-hOPGp-mOPG vector containing human OPG promoter and FLAG tag and to microinject vector into fertilized zygotes from C57BL/6J × CBA mice to prepare transgenic mice. The OPG transgenic positive mice were identified by PCR and western blotting. Twelve-week-old OPG transgenic mice (OPG-Tg mice) and wild-type mice (WT mice) were utilized in the study of bone microarchitecture. Microcomputed tomography (micro-CT) data showed that compared with WT mice, the tibia of OPG-Tg mice showed an increased volumetric BMD (vBMD), tissue BMD (tBMD), trabecular thickness (Tb.Th), and trabecular number (Tb.N), and a decreased trabecular separation (Th.Sp) (P<0.05) . The cortical bone microarchitecture parameters, such as cortical area (Ct.Ar), cortical thickness (Ct.Th), cortical BMD (Ct.BMD), cortical BMC (Ct.BMC), BMD, and BMC of femur, were increased, and the inner perimeter (In.Pm) was decreased, in OPG-Tg mice, compared to those in WT mice (P<0.05). The established OPG transgenic mouse model could be valuable for further studying the biological significance and gene regulation of OPG in vivo

A new approach for quantifying epithelial and stromal thickness changes after orthokeratology contact lens wear

The aim of the study was to develop an automatic segmentation approach to optical coherence tomography (OCT) images and to investigate the changes in epithelial and stromal thickness profile and radius of curvature after the use of orthokeratology (Ortho-K) contact lenses. A total of 45 right eyes from 52 participants were monitored before, and after one month of, uninterrupted overnight Ortho-K lens wear. The tomography of their right eyes was obtained using optical OCT and rotating Scheimpflug imaging (OCULUS Pentacam). A custom-built MATLAB code for automatic segmentation of corneal OCT images was created and used to assess changes in epithelial thickness, stromal thickness, corneal and stromal profiles and radii of curvature before, and after one month of, uninterrupted overnight wear of Ortho-K lenses. In the central area (0–2 mm diameter), the epithelium thinned by 12.8 ± 6.0 µm (23.8% on average, p < 0.01) after one month of Ortho-K lens wear. In the paracentral area (2–5 mm diameter), the epithelium thinned nasally and temporally (by 2.4 ± 5.9 µm, 4.5% on average, p = 0.031). The stroma thickness increased in the central area (by 4.8 ± 16.1 µm, p = 0.005). The radius of curvature of the central corneal anterior surface increased by 0.24 ± 0.26 mm (3.1%, p < 0.01) along the horizontal meridian and by 0.34 ± 0.18 mm (4.2%, p < 0.01) along the vertical meridian. There were no significant changes in the anterior and posterior stromal radius of curvature. This study introduced a new method to automatically detect the anterior corneal surface, the epithelial posterior surface and the posterior corneal surface in OCT scans. Overnight wear of Ortho-K lenses caused thinning of the central corneal epithelium. The anterior corneal surface became flattered while the anterior and posterior surfaces of the stroma did not undergo significant changes. The results are consistent with the changes reported in previous studies. The reduction in myopic refractive error caused by Ortho-K lens wear was mainly due to changes in corneal epithelium thickness profile

Interferon Impedes an Early Step of Hepatitis Delta Virus Infection

Hepatitis delta virus (HDV) infects hepatocytes, the major cell type of the liver. Infection of the liver may be either transient or chronic. The prognosis for patients with chronic HDV infection is poor, with a high risk of cirrhosis and hepatocellular carcinoma. The best antiviral therapy is weekly administration for at least one year of high doses of interferon alpha. This efficacy of interferon therapy has been puzzling in that HDV replication in transfected cell lines is reported as insensitive to administration of interferon alpha or gamma. Similarly, this study shows that even when an interferon response was induced by transfection of poly(IC) into a cell line, HDV RNA accumulation was only modestly inhibited. However, when the HDV replication was initiated by infection of primary human hepatocytes, simultaneous addition of interferons alpha or gamma at 600 units/ml, a concentration comparable to that achieved in treated patients, the subsequent HDV RNA accumulation was inhibited by at least 80%. These interferon treatments were shown to produce significant time-dependent increases of host response proteins such as for Stat-1, phosphoStat-1, Mx1/2/3 and PKR, and yet interferon pretreatment of hepatocytes did not confer an increased inhibition of HDV replication over interferon treatment at the time of (or after) infection. These and other data support the interpretation that interferon action against HDV replication can occur and is largely mediated at the level of entry into primary human hepatocytes. Thus in vivo, the success of long-term interferon therapy for chronic HDV, may likewise involve blocking HDV spread by interfering with the initiation of productive infection of naïve hepatocytes

Data-Driven Approach to Assess Street Safety: Large-Scale Analysis of the Microscopic Design

Safety is an important quality of street space that affects people’s psychological state and behavior in many ways. Previous large-scale assessment of street safety focuses more on social and physical factors and has less correlation with spatial design, especially the microscopic design. Limited by data and methods, street safety assessment related to microscopic design is mostly conducted on the small scale. Based on multisource big data, this study conducts a data-driven approach to assess the safety of street microscope design on a large scale from the perspective of individual perception. An assessment system including four dimensions of walkability, spatial enclosure, visual permeability, and vitality is constructed, which reflects the individual perceptions of the street space. Intraclass correlation coefficient (ICC) and location-based service (LBS) data are used to verify the effectiveness of the assessment method. The results show that multisource big data can effectively measure the physical elements and design features of streets, reflecting street users’ perception of vision, function, architecture, and street form, as well as the spatial selectivity based on their judgment of safety. The measurement of multidimensional connotations and the fusion of multiple data mining technologies promote the accuracy and effectiveness of the assessment method. Street safety presents the spatial distribution of high-value aggregation and low-value dispersion. Street safety is relatively low in areas with a large scale, lack of street interface, large amount of transit traffic, and high-density vegetation cover. The proposed method and the obtained results can be a reference for humanized street design and sustainable urban traffic planning and management

Positive Interaction between Transportation Hub and Urban Space in Mega-city. Redesign the Generation of Urban Design Strategies at Shanghai West Railway Station

Book of proceedings: Annual AESOP Congress, Definite Space – Fuzzy Responsibility, Prague, 13-16th July, 2015With the high-speed intercity passenger transportation gradually entering peopl definition of intercity railway transportation has been changing. Meanwhile, high-speed intercity passenger service station and the surrounding areas are still stuck in outdated facilities and chaotic image. The essay focus to figure out what is the positive interaction between transportation hub and urban space. It aims to provide people available and affordable transportation not only with traffic and infrastructure planning, but also with outstanding urban design quality and its Social Dimension. As the rapid development of China's mega-cities, Shanghai has a dominant role in transportation in the Yangtze River Delta region. Through the description of current situation between urban space and transportation hub at Shanghai West Railway Station, the redesign intends to put forward the challenges that Shanghai West Railway Station will face at present and in the future development, evaluate the transformation of the old city with concrete examples, design and bring forward the corresponding strategies in six aspects: space, transportation, function, form, ecology and the connection to the surrounding area, determine a more appropriate and more extensive updates and development from multiple angles on the basis of a variety of factors so as to improve the vitality of the region gradually. On this basis, this paper will make an objective analysis on how to enhance the quality of the environment around the station and along the railway and improve the split urban space caused by the rail lines, thus creating a more effective system design mode to make sustainable development in Shanghai West Railway Station area.Published Versio

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

A convenient synthetic procedure for the construction of novel dispirooxindole motifs was successfully developed by base-promoted three-component reaction of ammonium acetate, isatins and in situ-generated 3-isatyl-1,4-dicarbonyl compounds. The piperidine-promoted three-component reaction of ammonium acetate, isatins and the in situ-generated dimedone adducts of 3-ethoxycarbonylmethyleneoxindoles afforded mutlifunctionalized dispiro[indoline-3,2'-quinoline-3',3''-indoline] derivatives in good yields and with high diastereoselectivity. On the other hand, a similar reaction of the dimedone adducts of 3-phenacylideneoxindoles afforded unique dispiro[indoline-3,2'-pyrrole-3',3''-indoline] derivatives with a cyclohexanedione substituent. A plausible reaction mechanism is proposed to explain the formation of the different spirooxindoles

Cost-effectiveness of camrelizumab combined with chemotherapy in the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma in China

Objective This study aimed to investigate the cost-effectiveness of adding Chinese-developed anti-PD-1 antibody camrelizumab to first-line platinum-doublet chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma (L/M NPC) from the perspective of Chinese healthcare system.Design A Markov model consisting of four health states, progression-free survival, first progression survival, second progression survival and death, was built to simulate 3-week patient transitions over a 20-year horizon. A direct comparison between first-line camrelizumab in combination with gemcitabine plus cisplatin and gemcitabine plus cisplatin was performed by calculating transition probabilities from the CAPTAIN-1st trial. Costs and utilities were collected from the local public database and literature. One-way and probabilistic sensitivity analyses were employed to evaluate the robustness of the model.Setting The Chinese healthcare system perspective.Participants A hypothetical cohort of Chinese patients with pathologically diagnosed L/M NPC who had an Eastern Cooperative Oncology Group performance status of 0 or 1.Interventions First-line camrelizumab in combination with camrelizumab and gemcitabine plus cisplatin (CGP) versus gemcitabine plus cisplatin (GP).Primary outcome measure Cost, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER).Results The baseline analysis demonstrated that, compared with first-line GP, first-line CGP yields an effectiveness increase of 0.26 QALY, accompanied by an increment of US$6137.59 in healthcare cost. This results in an ICER of US$23 482.32/QALY. With the willingness-to-pay (WTP) threshold for a QALY set at US$37 654.50, first-line CGP proves to be cost-effective in 97.20% of the iterations. Deterministic sensitivity analyses indicated that the uncertainty in model parameters had no substantial effect on our results. Probability sensitivity analysis indicated that CGP was cost-effective at the assumed WTP threshold.Conclusion For Chinese patients with L/M NPC, adding Chinese-developed anti-PD-1 antibody camrelizumab to the first-line GP chemotherapy may be cost-effective