Eye-Preserving Therapies for Advanced Retinoblastoma: A Multicenter Cohort of 1678 Patients in China.

PURPOSE: This study attempted to estimate the impact of eye-preserving therapies for the long-term prognosis of patients with advanced retinoblastoma with regard to overall survival and ocular salvage. DESIGN: Retrospective cohort study covering all 31 provinces (38 retinoblastoma treating centers) of mainland China. PARTICIPANTS: One thousand six hundred seventy-eight patients diagnosed with group D or E retinoblastoma from January 2006 through May 2016. METHODS: Chart review was performed. The patients were divided into primary enucleation and eye-preserving groups, and they were followed up for survival status. The impact of initial treatment on survival was evaluated by Cox analyses. MAIN OUTCOME MEASURES: Overall survival and final eye preservation. RESULTS: After a median follow-up of 43.9 months, 196 patients (12%) died, and the 5-year overall survival was 86%. In total, the eyeball preservation rate was 48%. In this cohort, 1172 patients (70%) had unilateral retinoblastoma, whereas 506 patients (30%) had bilateral disease. For patients with unilateral disease, 570 eyes (49%) underwent primary enucleation, and 602 patients (51%) received eye-preserving therapies initially. During the follow-up (median, 45.6 months), 59 patients (10%) from the primary enucleation group and 56 patients (9.3%) from the eye-preserving group died. Multivariate Cox analyses indicated no significant difference in overall survival between the 2 groups (hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.85-1.84; P = 0.250). For patients with bilateral disease, 95 eyes (19%) underwent primary enucleation, and 411 patients (81%) received eye-preserving therapies initially. During the follow-up (median, 40.1 months), 12 patients (13%) from the primary enucleation group and 69 patients (17%) from the eye-preserving group died. For bilateral retinoblastoma with the worse eye classified as group E, patients undergoing primary enucleation exhibited better overall survival (HR, 2.35; 95% CI, 1.10-5.01; P = 0.027); however, this survival advantage was not evident until passing 22.6 months after initial diagnosis. CONCLUSIONS: Eye-preserving therapies have been used widely for advanced retinoblastoma in China. Patients with bilateral disease whose worse eye was classified as group E and who initially underwent eye-preserving therapies exhibited a worse overall survival. The choice of primary treatment for advanced retinoblastoma should be weighed carefully.

Molecular simulation of enhanced separation of humid air components using GO-PVA nanocomposite membranes under differential pressures.

Hydrophilic nanocomposite membranes have significant advantages in the separation of water vapor which is the core process in air dehumidification. This paper focuses on exploring the micro-mechanism of enhanced separation using graphene oxide-polyvinyl alcohol (GO-PVA) nanocomposite membranes. The sorption and diffusion behaviors of water vapor and nitrogen in GO-PVA membranes were investigated using molecular dynamics (MD) and Monte Carlo (MC) methods. The study showed that embedding GO into a PVA matrix results in a higher glass transition temperature and fractional free volume. The latter is believed to enhance the diffusivity of gas molecules in polymeric membranes. The interaction between the polymer chains and GO nanoparticles notably promotes the adsorption capacity of water vapor and inhibits nitrogen adsorption in the membrane. A water vapor permeance of 8844.07 Barrer and a separation factor of 3.53 could be achieved with the GO-PVA-0.5 membrane. The analysis confirmed that GO has the same effect on single gas and binary gas mixtures, i.e., increasing the water vapor permeability and selectivity. The calculated water vapor permeance of binary gas is 83% lower than that of single gas permeation. It is expected that this research could provide fundamentals for the optimization and synthesis of gas separation membranes.

Phosphine-catalyzed regiospecific (3 + 2) cyclization of 3-nitroindoles with allene esters.

A phosphine-catalyzed regiospecific (3 + 2) cyclization of 3-nitroindoles with allene esters has been established, which constructed indole-fused five-membered rings in good yields (up to 86%). This reaction serves as a powerful method for the construction of indole-fused five-membered rings. In addition, this reaction provides a useful strategy toward settling the challenge of utilizing other 1,3-dipoles or 1,3-dipole surrogates to perform (3 + 2) cyclizations with 3-nitroindoles in different catalytic modes, which will enrich the chemistry of nitroindoles and catalytic asymmetric dearomatization cyclizations.

Binocular treatment for individual with amblyopia: A systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy of binocular treatment for individual with amblyopia. METHODS: In this meta-analysis, a comprehensive search of literatures was performed from PubMed, Embase, Cochrane Library and Web of Science databases up to December 21, 2020. Sensitivity analysis was performed for all outcomes. The Begg's test was used to assess the publication bias. Heterogeneity test was conducted for each effect indicator. Indicators were analyzed by random-effects model when the heterogeneity statistic I2 ≥ 50%, on the contrary, indicators were analyzed by fixed-effect model. Standard mean difference (SMD) or weighted mean difference (WMD) was adopted as effect indicators, and the effect amount was expressed as 95% confidence intervals (CIs). RESULTS: A total of 13 literatures including 1146 participants were finally enrolled, with 595 in the intervention group and 551 in the control group. The results indicated that the improvement of amblyopic eye visual acuity [SMD: 0.882, 95%CI: (0.152, 1.613), P = 0.018] in binocular treatment group was better than that in control group. And binocular treatment could improve stereo acuity in individual with amblyopia [WMD: 0.138, 95%CI: (0.068, 0.208), P < 0.001]. CONCLUSION: Binocular treatment may be beneficial to visual acuity, stereo acuity and binocular function improvement for individual with amblyopia. In clinical practice, binocular treatment can be used as one of the treatments for individual with amblyopia.

A Review on the Morphology and Material Properties of the Gas Separation Membrane: Molecular Simulation.

Gas membrane separation technology is widely applied in different industry processes because of its advantages relating to separation performance and economic efficiency. It is usually difficult and time consuming to determine the suitable membrane materials for specific industrial separation processes through traditional experimental research methods. Molecular simulation is widely used to investigate the microscopic morphology and macroscopic properties of materials, and it guides the improvement of membrane materials. This paper comprehensively reviews the molecular-level exploration of the dominant mechanism and influencing factors of gas membrane-based separation. The thermodynamics and kinetics of polymer membrane synthesis, the molecular interactions among the penetrated gases, the relationships between the membrane properties and the transport characteristics of different gases in the composite membrane are summarized and discussed. The limitations and perspectives of the molecular simulation method in the study of the gas membrane separation process are also presented to rationalize its potential and innovative applications. This review provides a more comprehensive reference for promoting the materials' design and engineering application of the gas separation membrane.

Second hit impels oncogenesis of retinoblastoma in patient-induced pluripotent stem cell-derived retinal organoids: direct evidence for Knudson's theory.

Retinoblastoma (Rb) is a type of malignant tumor due to abnormal retinogenesis with biallelic mutations of the RB1 gene. Its pathogenesis has been proposed as a "two-mutation hypothesis" by Knudson since 1971; however, there remain some debates on disease onset sufficiency of the biallelic RB1 mutations. To obtain straightforward evidence for this hypothesis, we investigated whether two-hit mutations of the RB1 gene drive tumorigenesis in patient-induced pluripotent stem cell (hiPSC)-derived human retinal organoids (hROs) and whether single allelic mutation hiPSC-derived hROs exhibit molecular and cellular defects. We generated hiPSCs with a heterozygous germline mutation (RB1m1/ wt ) from a Rb patient. A second-allele RB1 gene mutation was knocked in to produce compound heterozygous mutations (RB1m1/m2 ) in the hiPSCs. These two hiPSC lines were independently developed into hROs through a stepwise differentiation. The hiPSC-RB1m1/m2 derived organoids demonstrated tumorigenesis in dishes, consistent with Rb profiles in spatiotemporal transcriptomes, in which developmentally photoreceptor fate-determining markers, CRX and OTX2, were highly expressed in hiPSC-RB1m1/m2 derived hROs. Additionally, ARR3+ maturing cone precursors were co-labeled with proliferative markers Ki67 or PCNA, in agreement with the consensus that human Rb is originated from maturing cone precursors. Finally, we demonstrated that retinal cells of hROs with monoallelic RB1 mutation were abnormal in molecular aspects due to its haploinsufficiency. In conclusion, this study provides straightforward supporting evidence in a way of reverse genetics for "two-hit hypothesis" in the Rb tumorigenesis and opens new avenues for development of early intervention and treatment of Rb.

Tylectomy Safety in Salvage of Eyes with Retinoblastoma.

Intraocular surgery is tabooed in retinoblastoma management, due to the concern of lethal extraocular spread. We reviewed the outcomes of consecutive children with intraocular retinoblastoma diagnosed at 29 Chinese centers between 2012-2014. We compared the outcomes of three categories of treatment: eye salvage including tylectomy (Group I), eye salvage without tylectomy (Group II), and primary enucleation (Group III). A total of 960 patients (1243 eyes) were diagnosed: 256 in Group I, 370 in Group II, and 293 in Group III; 41 patients abandoned treatment upfront. The estimated 5-year overall survivals (OS) were, for Group I, 94%, for Group II 89%, and for Group III 95%. The estimated 5-year disease-specific survivals (DSS) were, for Group I, 96%, for Group II 90%, and for Group III 95%. Patients in Group I had a significantly higher 5-year DSS than patients in Group II (p = 0.003) and not significantly different than patients in Group III (p = 0.367). Overall survival was not compromised by the inclusion of tylectomy in eye salvage therapy compared to eye salvage without tylectomy or primary enucleation. Disease-specific survival was better when tylectomy was included in eye salvage treatments. Tylectomy as part of multimodal treatment may contribute to the care of retinoblastoma patients with chemotherapy-resistant tumor, eyes with concomitant ocular complications, or at the risk of treatment abandonment.

Fundus examination of 199 851 newborns by digital imaging in China: a multicentre cross-sectional study.

BACKGROUND: The prevalence of ocular abnormalities of newborn in China has seldom been reported. To report the implementation of digital imaging in ocular screening of all newborns in multiple centres in China and to describe the abnormal findings of fundus examination, we did the cross-sectional study. METHODS: Fundus examinations were performed on newborns within the 42 days after birth using a RetCam wide-field digital imaging system. Digital images of the posterior pole, superior, nasal and temporal retinal fields of each participant were taken. All newborns were from eights centres across China from January 2009 to July 2017. RESULTS: A total of 199 851 newborns were included in the study. We detected 18 198 (9.11%) abnormal cases. The most frequent abnormality was severe retinal haemorrhage (RH) found in 12 810 cases (6.41%). The other anomalies included familial exudative vitreoretinopathy, retinopathy of prematurity, abnormal fundus pigmentation, subconjunctival haemorrhage, choroidal coloboma, idiopathic retinal venous tortuosity, exudative changes and other anomalies with uncertain identities. CONCLUSION: This large-scale study of newborn fundus examination showed a relatively high prevalence of ocular abnormalities. Hundreds of neonates with rare disorders that severely impair ocular health were also detected at an early age. The long-term impact of other anomalies including RHs on the ocular system should be investigated by a perspective study. Our study suggested that fundus examination of newborns can play a beneficial role in ocular health.

Retrospective investigation of retinoblastoma in Chinese patients.

This is a retrospective investigation of patients with Retinoblastoma (RB) conducted from 2013 to 2016 at the Quanzhou Maternal and Child Health Hospital (China). Demographic and clinical characteristics, treatment outcomes, and risk factors were studied. In total, 436 patients were included in the study. Most of the findings obtained in this study are consistent with other previous reports. The male: female ratio was 1.41:1, and the unilateral: bilateral ratio was 1.51:1. Leukocoria was the most common presenting sign (79.44%), followed by strabismus (12.38%). While, the overall rates of enucleation (15.82%) and mortality (0.92%) were markedly lower than in other reports of RB in Chinese, and most of the patients received conservative therapy. There were signficant differences (p < 0.001) in the age of at first sign and diagnosis, and treatment modalities between patients with bilateral and unilateral RB. The treatment modalities did not show a specific trend over the 3-year study period. Our results suggest that an incorrect initial diagnosis and long lag time may be risk factors for ineffective treatment and a poor prognosis in patients with RB. This was a comprehensive retrospective investigation in which the sample size exceeded most previous retrospective investigations of RB. Our study confirmed that early detection, accurate diagnosis, and active intervention are conducive to control of retention of patients' vision. Fundus examinations, education regarding the early signs of RB, and optimization of the therapeutic strategy of RB may play important roles in ocular health.