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.

Identification of differentially expressed long non-coding RNAs and mRNAs in orbital adipose/connective tissue of thyroid-associated ophthalmopathy.

Extracellular matrix remodeling and orbital adipose/connective tissue expansion are two key features of thyroid-associated ophthalmopathy (TAO). Recent studies have indicated the critical role of long non-coding RNAs (lncRNAs) in the pathogenesis of ocular disorders. However, little is known about the roles of lncRNAs in orbital adipose/connective tissue of TAO. In this study, the profiles of lncRNAs and mRNAs in the orbital adipose/connective tissue of TAO were identified by RNA sequencing. A total of 809 differential lncRNAs and 607 differential mRNAs were identified, among which 52 genes were found to be significantly related to the extracellular matrix. Co-expression network analysis suggested that lncRNAs might regulate extracellular matrix remodeling in orbital adipose/connective tissue of TAO. Additionally, the target genes of lncRNAs involved in the lipid metabolism and cytokine-cytokine receptor interaction were also identified. These results may provide potential regulatory mechanisms of lncRNAs in the orbital adipose/connective tissue of TAO.

Effect of early prophylactic low-dose recombinant human erythropoietin on retinopathy of prematurity in very preterm infants.

BACKGROUND: Very preterm infants are at risk of developing retinopathy of prematurity (ROP). Recombinant human erythropoietin (rhEPO) is routinely used to prevent anemia in preterm infants; however, the effect of rhEPO on ROP development is still controversial. The purpose of this study was to evaluate the effect of early prophylactic low-dose rhEPO administration on ROP development in very preterm infants. METHODS: A total of 1898 preterm infants born before 32 weeks of gestation were included. Preterm infants received rhEPO (n = 950; 500 U/kg, rhEPO group) or saline (n = 948, control group) intravenously within 72 h of birth and then once every other day for 2 weeks. RESULTS: The total incidence of ROP was not significantly different between the two groups (10.2% vs. 13.2%, p = 0.055). Further analysis showed that rhEPO group had lower rates of type 2 ROP than the control group (2.2% vs. 4.1%, RR 0.98; 95% CI 0.96-1.00; p = 0.021). Subgroup analysis found that rhEPO treatment significantly decreased the incidence of type 2 ROP in infant boys (1.8% vs. 4.3%, p = 0.021) and in those with a gestational age of 28-296/7 weeks (1.1% vs. 4.9%, p = 0.002) and birth weight of 1000-1499 g (1.2% vs. 4.2%, p = 0.002). There was a small increasing tendency for the incidence of ROP in infants with a gestational age of < 28 weeks after rhEPO treatment. CONCLUSIONS: Repeated low-dose rhEPO administration has no significant influence on the development of ROP; however, it may be effective for type 2 ROP in infant boys or in infants with gestational age > 28 weeks and birth weight > 1500 g. Trial registration The data of this study were retrieved from two clinical studies registered ClinicalTrials.gov (NCT02036073) on January 14, 2014, https://clinicaltrials.gov/ct2/show/NCT02036073 ; and (NCT03919500) on April 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03919500 .

Differentially expressed circular RNAs in orbital adipose/connective tissue from patients with thyroid-associated ophthalmopathy.

Our study aimed to investigate the differentially expressed circRNAs and their potential roles in orbital adipose/connective tissue from patients with thyroid-associated ophthalmopathy (TAO). The orbital adipose/connective tissue samples from three TAO patients and three control individuals were collected for RNA sequencing after depletion of ribosomal RNA. Differentially expressed mRNAs and up-regulated circRNAs were used for co-expression analysis. Functional and pathway enrichment analysis were conducted for the up- and down-regulated mRNAs in the circRNA-mRNA co-expression network. Meanwhile, circRNA-miRNA interaction network was established by miRanda software. The expression levels of mRNAs and circRNAs in control and TAO samples were determined by qRT-PCR. Among all the 16,329 circRNAs predicted from RNA sequencing data, 163 circRNAs (95 down-regulated and 68 up-regulated) were differentially expressed in TAO samples. Besides, 607 differentially expressed mRNAs were identified. The co-expression analysis showed circRNA_14940 was correlated with CCND1 and TNXB, while circRNA_10135 was correlated with PTGFR, and circRNA_14936 was correlated with TNFRSF19. The up-regulated CCND1 participated in Wnt signaling pathway. The down-regulated TNXB was involved in the ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathway. PTGFR participated in neuroactive ligand-receptor interaction and calcium signaling pathway. TNFRSF19 was involved in cytokine-cytokine receptor interaction. In the interaction network, circRNA_14936 could interact with hsa-miR-10392-3p, and circRNA_12367 could interact with hsa-miR-1228-3p. Moreover, the expression changes of MMP2, TNXB, PTGFR, CCND1, and TNFRSF19, as well as circRNA_14936, circRNA_14940, and circRNA_12367 were validated by qRT-PCR. In conclusion, the differentially expressed circRNAs might participate in pathogenesis of TAO, and we speculated that circRNA_14940-CCND1-Wnt signaling pathway might be an important regulatory axis.

Integrative transcriptomics and proteomic analysis of extraocular muscles from patients with thyroid-associated ophthalmopathy.

Our study aimed to reveal the underlying pathologic mechanisms of thyroid-associated ophthalmopathy (TAO) by integrative transcriptomics and proteomic analysis of extraocular muscles (EOM). The study involved 11 TAO patients (clinical activity score ≤ 2) and 11 control donors. Total RNA was extracted from EOM samples of 5 TAO patients and 5 control individuals for gene microarray analysis to reveal differentially expressed genes. Concurrently, EOM samples from 3 TAO patients and 3 control individuals were lysed for quantitative proteomic analysis. Differentially expressed genes and proteins were identified, followed by functional and pathway enrichment analysis and protein-protein interaction network construction. Concordance between proteins and transcripts was examined, and functional annotations were conducted. Expressions of versican (VCAN) and lipocalin 1 (LCN1) in EOM samples from another 3 TAO patients and 3 control individuals were measured by western blotting. In total, 952 genes and 137 proteins were identified as differentially expressed, as well as 96 differentially expressed proteins without significantly changed mRNA abundance. Proteins mainly related to the composition (such as MYH1, MYH2, and MYH13) and contraction force (MYH3, MYH8, ACTN3, and TNNT1) of the muscle fibers were significantly up-regulated in EOM samples of TAO, as well as those (such as VCAN, MPZ, and PTPRC) associated with cell adhesion. In addition, differentially expressed proteins related to the components and metabolism of extracellular matrix (ECM) (such as COL1A1, COL1A2, COL2A1, VCAN, OGN, and DCN) were identified. Similarly, expressions of genes involved in cell adhesion and ECM metabolism were significantly different between EOM samples of TAO patients and controls. Western blotting verified that VCAN involved in ECM proteoglycans and diseases associated with glycosaminoglycan metabolism was markedly higher in EOM samples of TAO, whereas LCN1 was obviously decreased. In conclusion, this study demonstrated the significantly altered cellular components of EOM, muscle contraction, cell adhesion and ECM metabolism, which might be involved in the pathologic mechanisms and/or consequences of TAO.

The Biological Effect and Clinical Application of Long Noncoding RNAs in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common malignancies in the world. Easier recurrence and metastasis is the main cause of mortality in CRC patients, and the markers applied for diagnosis and treatment of CRC is still urgently needed to early diagnose and evaluate therapeutic effect. Long noncoding RNA (lncRNA) is a class of noncoding RNA that the length is more than 200 nucleotides. With the development of sequencing technique about transcriptome, increasing lncRNAs are focused on their function and mechanism related to the nosogenesis and pathology of CRC. Recent studies report that lncRNAs acted as crucial role in CRC and could be as biomarker for CRC diagnosis and treatment. In this review, we display the regulation of lncRNA by interacting with DNA, RNA and protein and highlight the double role of lncRNAs as oncogene or anti-tumor gene involved in Wnt signaling pathway, p53 signaling pathway or others to be an regulator in CRC development. Lastly, we discuss some new finding of lncRNAs, especially lncRNA in exosome, which could be as potential markers for diagnosis and treatment of CRC in future.

Distinct mutations with different inheritance mode caused similar retinal dystrophies in one family: a demonstration of the importance of genetic annotations in complicated pedigrees.

BACKGROUND: Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy presenting remarkable genetic heterogeneity. Genetic annotations would help with better clinical assessments and benefit gene therapy, and therefore should be recommended for RP patients. This report reveals the disease causing mutations in two RP pedigrees with confusing inheritance patterns using whole exome sequencing (WES). METHODS: Twenty-five participants including eight patients from two families were recruited and received comprehensive ophthalmic evaluations. WES was applied for mutation identification. Bioinformatics annotations, intrafamilial co-segregation tests, and in silico analyses were subsequently conducted for mutation verification. RESULTS: All patients were clinically diagnosed with RP. The first family included two siblings born to parents with consanguineous marriage; however, no potential pathogenic variant was found shared by both patients. Further analysis revealed that the female patient carried a recurrent homozygous C8ORF37 p.W185*, while the male patient had hemizygous OFD1 p.T120A. The second family was found to segregate mutations in two genes, TULP1 and RP1. Two patients born to consanguineous marriage carried homozygous TULP1 p.R419W, while a recurrent heterozygous RP1 p.L762Yfs*17 was found in another four patients presenting an autosomal dominant inheritance pattern. Crystal structural analysis further indicated that the substitution from arginine to tryptophan at the highly conserved residue 419 of TULP1 could lead to the elimination of two hydrogen bonds between residue 419 and residues V488 and S534. All four genes, including C8ORF37, OFD1, TULP1 and RP1, have been previously implicated in RP etiology. CONCLUSIONS: Our study demonstrates the coexistence of diverse inheritance modes and mutations affecting distinct disease causing genes in two RP families with consanguineous marriage. Our data provide novel insights into assessments of complicated pedigrees, reinforce the genetic complexity of RP, and highlight the need for extensive molecular evaluations in such challenging families with diverse inheritance modes and mutations.

GUCA1A mutation causes maculopathy in a five-generation family with a wide spectrum of severity.

PURPOSE: The aim of this study was to investigate the genetic basis and pathogenic mechanism of variable maculopathies, ranging from mild photoreceptor degeneration to central areolar choroidal dystrophy, in a five-generation family. METHODS: Clinical characterizations, whole-exome sequencing, and genome-wide linkage analysis were carried out on the family. Zebrafish models were used to investigate the pathogenesis of GUCA1A mutations. RESULTS: A novel mutation, GUCA1A p.R120L, was identified in the family and predicted to alter the tertiary structure of guanylyl cyclase-activating protein 1, a photoreceptor-expressed protein encoded by the GUCA1A gene. The mutation was shown in zebrafish to cause significant disruptions in photoreceptors and retinal pigment epithelium, together with atrophies of retinal vessels and choriocapillaris. Those phenotypes could not be fully rescued by exogenous wild-type GUCA1A, suggesting a likely gain-of-function mechanism for p.R120L. GUCA1A p.D100E, another mutation previously implicated in cone dystrophy, also impaired the retinal pigment epithelium and photoreceptors in zebrafish, but probably via a dominant negative effect. CONCLUSION: We conclude that GUCA1A mutations could cause significant variability in maculopathies, including central areolar choroidal dystrophy, which represents a severe pattern of maculopathy. The diverse pathogenic modes of GUCA1A mutations may explain the phenotypic diversities.Genet Med advance online publication 26 January 2017.

Maternal germline mosaicism of kinesin family member 21A (KIF21A) mutation causes complex phenotypes in a Chinese family with congenital fibrosis of the extraocular muscles.

PURPOSE: To identify the causative mutation with its possible origin in a Chinese family with congenital fibrosis of extraocular muscles type 1 (CFEOM1) and to characterize the ocular phenotypes and lesions in the corresponding intracranial nerves. METHODS: Three affected siblings and their asymptomatic parents underwent comprehensive ophthalmic examinations and neuropathologic analysis involving magnetic resonance imaging (MRI). KIF21A, PHOX2A, and TUBB3 genes were sequenced on the leukocyte-derived DNA to detect variants. The disease-linked haplotype was analyzed using four microsatellite markers across the KIF21A locus. RESULTS: All three affected individuals displayed typical CFEOM1. MRI revealed complicated but consistent neuromuscular abnormalities in the two patients examined, including hypoplastic oculomotor nerves, complete absence of bilateral superior rectus muscles, and unilateral absence of the abducens nerve with marked atrophy of the corresponding lateral rectus muscle. A heterozygous hotspot mutation KIF21A c.2860C>T was identified in all patients, but it was absent in both parents. Haplotype analysis of the disease locus showed the likely maternal inheritance of the disease-associated haplotype to all three affected offspring, strongly suggesting maternal germline mosaicism of the mutation. CONCLUSIONS: Germline mosaicism of KIF21A c.2860C>T is likely to cause the high occurrence of this mutation in the population. This information may be useful for genetic counseling. KIF21A mutations can affect the abducens nerve and cause complete absence of the bilateral superior rectus muscles. MRI characterization of new CFEOM1 phenotypes would assist clinical management.

Design and control of a novel variable stiffness actuator based on antagonistic variable radius principle.

Variable stiffness actuators (VSAs) are essential for ensuring safe human-robot interactions in robotic applications. This paper proposes a novel rotary VSA using an antagonistic Hoberman linkage mechanism (AHLM), which offers a large stiffness range and a compact structure. The VSA-AHLM consists of two sets of antagonistic-type quadratic springs based on spiral cams connected to the Hoberman linkage mechanism (HLM) through four cables. By simultaneously adjusting both the radius of the HLM and the spring preload, the stiffness of the VSA-AHLM can be varied within a large range. Furthermore, the position and stiffness of the VSA-AHLM can be controlled independently by two rotary motors. The geometric parameters of the spiral cam are determined to achieve the desired linear stiffness-elongation behavior of a quadratic spring, and detailed models of the actuator's stiffness, elastic energy, and torque are established. An actuator prototype is fabricated to demonstrate the proposed variable stiffness approach. Experiments show that the developed actuator can achieve significant stiffness changes and exhibits excellent positioning and trajectory tracking performance.

PRMT5 promotes retinoblastoma development.

Epigenetic mechanism, including DNA methylation and histone modifications, contributes to alterations in the expression patterns of genes regulating malignant phenotype of cancer cells. However, the epigenetic modulation of vascular endothelial growth factor-A (VEGFA) in retinoblastoma (RB) has not been clearly established. We aimed to examine the epigenetic regulation of VEGFA by protein arginine methyltransferase 5 (PRMT5) in RB. Using the GEO database, we identified VEGFA as a pathogenic gene in RB. Silencing of VEGFA in SO-RB50 and Y79 cells inhibited cell proliferation, angiogenesis, and migration, promoted apoptosis, and suppressed tumor growth in mice. Mechanistically, PRMT5 promoted H3K4me3 modification of the VEGFA promoter, thereby activating VEGFA expression. VEGFA could regulate the expression of MMP1, MMP2, and MMP9. Further silencing of VEGFA in RB cells overexpressing PRMT5 constrained the expression of MMP1, MMP2 and MMP9, and suppressed the growth of tumors in mice. In conclusion, this study clarifies that the depletion of PRMT5 reduces H3K4me3-mediated VEGFA transcription and retards the carcinogenesis of RB by suppressing the expression of MMPs.

Design and analysis of a passive exoskeleton with its hip joint energy-storage.

A novel passive hip exoskeleton has been designed and built with the aim of reducing metabolic consumption during walking by a passive way of storing the negative mechanical energy in the deceleration phase and releasing it in the acceleration phase. A ratchet spiral spring mechanism with a set of double stable switches is designed inside the exoskeleton for the above purpose. An analysis is conducted on the mechanism and the switching timing for the energy management to automatically store or release the energy according to the biomechanics of walking. In addition, a gravity-balance mechanism embedded inside the exoskeleton is designed as well to minimize the influence of the lower limb weight on muscle work. Human-exoskeleton interaction has been studied using the Opensim software, and simulation results demonstrated the effectiveness of the exoskeleton in reducing metabolic consumption during walking. An exoskeleton prototype has been built and tested with experiments measuring assistive torque and surface electromyography signal, confirming the effectiveness of the gravity-balance mechanism and energy-storage method, as well as the exoskeleton's actual assistive effect.

Systemic conbercept pharmacokinetics and VEGF pharmacodynamics following intravitreal injections of conbercept in patients with retinopathy of prematurity.

BACKGROUND: Data on serum vascular endothelial growth factor (VEGF) and drug levels in patients with retinopathy of prematurity (ROP) following intravitreal injections of conbercept (IVC) are lacking. METHODS: Multicentre, prospective, non-randomised study of patients with aggressive posterior retinopathy of prematurity (APROP) or type 1 ROP who had not received other treatment. All infants received therapy in both eyes plus intravitreal IVC 0.25 mg/0.025 mL in one eye and had at least 6 months of follow-up. Blood samples were collected before and 1 week and 4 weeks after IVC. The main outcome measures were serum conbercept and VEGF concentrations. RESULTS: Forty infants with APROP or type 1 ROP were enrolled. The mean serum VEGF at baseline and 1 week and 4 weeks after a total of 0.25 mg of IVC was 953.35±311.90 pg/mL, 303.46±181.89 pg/mL and 883.12±303.89 pg/mL, respectively. Serum VEGF 1 week after IVC was significantly lower (p<0.05) than baseline, and at 4 weeks after IVC, it was significantly higher (p<0.05) than at 1 week. There was no significant difference (p>0.05) between baseline and 4 weeks. Serum conbercept was below the limit of quantitation (BLOQ) at baseline and 4 weeks and was 19.81±7.60 ng/mL at 1 week. CONCLUSION: Serum VEGF 1 week after IVC was significantly lower than baseline but returned to baseline at 4 weeks. Serum conbercept increased at 1 week and was BLOQ at 4 weeks.

Outcomes of a Simple Lateral Rectus Belly Transposition Procedure Combined With Ipsilateral Antagonist Recession for Vertical Rectus Palsy.

PURPOSE: To report the surgical effects of a combination treatment comprising the lateral rectus belly transposition (LRBT) procedure, without muscle splitting or disinsertion, and ipsilateral antagonist recession for vertical rectus palsy. METHODS: The medical records of consecutive patients who underwent the LRBT procedure between 2017 and 2020 were reviewed. Preoperative and postoperative deviation in primary position, preoperative and postoperative scale of duction of the palsied muscle, any induced horizontal or torsional deviation, and other complications were collected. RESULTS: Thirteen patients were identified: 10 with inferior rectus palsy and 3 with superior rectus palsy. The mean postoperative follow-up time was 20.4 ± 8.0 months. Eleven patients (84.6%) underwent simultaneous recession of the ipsilateral antagonist muscle of the palsied vertical rectus. After surgery, the mean vertical deviation improved from 31.4 ± 16.4 to 1.9 ± 3.6 prism diopters (PD) (P < .001). The mean vertical duction limitation of the palsied muscle improved from -2.7 ± 0.6 to -0.6 ± 0.5 (P = .001). In one patient, the scleral fixation suture was removed due to continuous reverse vertical diplopia. The total success rate was 76.9%. No induced horizontal deviation was noted. Anterior segment ischemia or other severe surgical complications did not occur. CONCLUSIONS: The LRBT procedure can be effective, safe, and reversible in patients with vertical rectus palsy. It allows for the option of simultaneous ipsilateral antagonist recession, and it is especially valuable in patients whose vertical duction deficiency is worse in abduction but mild in adduction. [J Pediatr Ophthalmol Strabismus. 2022;59(6):396-404.].

SP2509, a Selective Inhibitor of LSD1, Suppresses Retinoblastoma Growth by Downregulating ß-catenin Signaling.

Purpose: To study the role of lysine-specific demethylase 1 (LSD1) in retinoblastoma (RB) growth and to determine whether the LSD1 inhibitor SP2509 can inhibit RB progression. Methods: We detected the levels of LSD1 in 12 RB tissue samples, two RB cell lines (Y79 and Weri-RB1), and a retinal pigment epithelium cell line (ARPE-19). Overexpression or knockdown of LSD1 was performed to examine the role of LSD1 in RB cancer cell survival. In vitro and in vivo experiments were conducted to detect the antitumor effect of SP2509, and the antitumor mechanism of SP2509 was examined by RNA sequencing and Western blot. Results: LSD1 is overexpressed in RB tissues and cells and increases RB cancer cell viability and colony formation ability. The LSD1 inhibitor SP2509 inhibits RB cell proliferation in vitro and in vivo. Treatment with SP2509 increases the levels of dimethylated histone 3 lysine 4 (H3K4me2) and inhibits the expression of ß-catenin signaling pathway-related proteins in RB cells. Conclusions: We demonstrated that LSD1 is overexpressed in RB cells and promotes RB cell survival. The LSD1 inhibitor SP2509 exerted strong growth inhibition in vitro and in vivo, which was at least partially mediated by suppression of the ß-catenin pathway.

Contemporary Update of Retinoblastoma in China: Three-Decade Changes in Epidemiology, Clinical Features, Treatments, and Outcomes.

PURPOSE: To report three-decade changes of clinical characteristics, progress of treatments, and risk factors associated with mortality and enucleation in patients with retinoblastoma in China. DESIGN: Retrospective cohort study. METHODS: This multicenter study included 2552 patients diagnosed with retinoblastoma in 38 medical centers in 31 provinces in China from 1989 to 2017, with follow-up data. Kendall's tau-b value was used to describe correlation coefficients between the three eras (between 1989 and 2008, between 2009 and 2013, and between 2014 and 2017) and clinical or demographic features. Hazard ratios and odds ratios were applied to measure risk factors. RESULTS: A total of 324 (13%) patients died and 1414 (42%) eyes were removed. The 1-year, 3-year, and 5-year overall survival rates were 95%, 86%, and 83%, respectively. Patients were diagnosed at a better stage by International Classification for Retinoblastoma over time (Kendall's tau-b value = -0.084, P < .001). Pathological risk factors were also observed less in recent eras. New conservative therapies were adopted and used in more patients. The eye removal rate gradually decreased (Kendall's tau-b value = -0.167, P < .001). The overall survival rates were 81%, 83%, and 91% in the three eras. By multivariate Cox regression, bilateral tumors and extraocular extension were identified as risk factors for death. Among intraocular disease, Group E indicated higher risk of mortality. By multivariate logistics regression, unilateral tumors, earlier era of diagnosis, and extraocular extension were risk factors for eye salvage failure. Among intraocular retinoblastoma, Groups D and E had higher risk of eye salvage failure. CONCLUSIONS: Patients were diagnosed at an earlier stage in recent eras. Conservative therapies, including intra-arterial chemotherapy, were increasingly being used. The above changes may contribute to the decreasing enucleation rate. Although no significant impact was identified on the mortality by the three eras, a decreasing trend was shown.

Differential expression and alternative splicing of transcripts in orbital adipose/connective tissue of thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy is a typical autoimmune disease of orbital tissues. Alternative splicing significantly influences many diseases progression, including cancer, age-related macular degeneration, and multiple sclerosis, by modulating the expression of transcripts. However, its role in thyroid-associated ophthalmopathy is still unclear. In this study, differential expression transcripts and differential alternative splicing genes in orbital adipose/connective tissues of thyroid-associated ophthalmopathy patients were detected using RNA sequencing, Cuffdiff, and replicate multivariate analysis of transcript splicing. Three thousand ninety six differential expression transcripts and 2355 differential alternative splicing genes were screened out, while functional enrichment analysis indicated that differential expression transcript and differential alternative splicing genes were associated with immune modulation, extracellular matrix remodeling, and adipogenesis. The expression of the SORBS1, SEPT2, COL12A1, and VCAN gene transcripts was verified by qRT-PCR. In conclusion, prevalent alternative splicing is involved in the disease development in thyroid-associated ophthalmopathy. More attention should be paid to the mechanism of alternative splicing to explore more potential therapeutic targets in thyroid-associated ophthalmopathy.

Outcomes of modified vertical rectus belly transposition versus augmented superior rectus transposition for chronic abducens nerve palsy.

PURPOSE: To compare the surgical outcomes of modified vertical rectus belly transposition (mVRBT) and medial rectus recession (MRc) versus augmented superior rectus transposition (aSRT) and MRc in Chinese patients with chronic abducens nerve palsy. METHODS: The medical records of patients with chronic abducens nerve palsy who underwent mVRBT/MRc or aSRT/MRc were retrospectively reviewed. Pre- and postoperative deviation in primary position, pre- and postoperative abduction limitation, and complications were recorded. Follow-up was at least 6 months. RESULTS: A total of 26 patients (mean age, 37.9 ± 19.6 years; 16 males [62%]) were included. Fourteen patients underwent mVRBT/MRc (mVRBT group) and 12 underwent aSRT/MRc (aSRT group). Both groups had similar amounts of recession (t = 0.27; P = 0.79). After surgery, statistically significant changes of abduction limitation and esotropia were observed (both P < 0.05). However, the difference in abduction improvement between groups was not statistically significant (mVRBT vs aSRT, 2.3 ± 0.91 vs 2.3 ± 0.97; t = 0.10, P = 0.92). Of the 19 patients who underwent unilateral surgery, preoperative esotropia was similar in both groups (t = 1.3; P = 0.21), but more esotropia was corrected in the mVRBT group than in the aSRT group (mVRBT vs aSRT, 57.8Δ ± 14.3Δ vs 44.6Δ ± 9.8Δ; t = 2.1; P = 0.047). There was no symptomatic vertical or torsional deviation. CONCLUSIONS: In our patient cohort, mVRBT/MRc showed a better effect in correcting esotropia and a similar effect in improving abduction limitation compared with aSRT/MRc.

Injury of photoreceptors and retinal pigment epithelium in macular area of a preterm infant: A case analysis.

RATIONAL: Injury of photoreceptors and retinal pigment epithelium (RPE) in macular area of premature infants is very rare. PATIENT CONCERNS: A preterm infant delivered under general anesthesia. The infant was born at 28 weeks' and 4 days' gestation, with a birth weight of 1.15 kg and a treatment of oxygen inhalation after birth. According to the related protocol formulated by the Ophthalmology Branch of the Chinese Medical Association in 2014, the infant was regularly checked in our hospital. DIAGNOSIS: Optical coherence tomography (OCT) examination showed injuries of the photoreceptors and RPE in macular area. INTERVENTIONS: The fundus screening at 40 weeks' and 4 days' gestation (corrected gestational age) showed retinopathy of prematurity in bilateral eyes, with round yellow-white lesions at the macular area of right eye and sub-temporal macular area. OCT examination showed interrupted signals in the external limiting membrane (ELM), inner segment of the photoreceptors (IS)/outer segment of the photoreceptors (OS) layer, interdigitation zone (IZ), and RPE of the central fovea of macula of the right eye, with the area of defect of approximately 184 µm. Enhanced signal reflection was found under the defect area. Interrupted signals were also found in the IS/OS layer of the central fovea of macula of the left eye, with the area of defect of approximately 222 µm. Fundus fluorescence angiography (FFA) examination showed transmitted fluorescence at the macular area of the right eye and sub-temporal macular area of the left eye, suggesting retinopathy of prematurity in bilateral eyes. OUTCOMES: Several factors, such as photic damage, eye injuries, hyperpyrexia, and underlying diseases, could cause macular retinal injuries. However, the baby had not received any radiation from high energy intense light sources, and had no history of hyperpyrexia or trauma. Fundamental screening was performed 1 year and 4 months of age and no obvious change was found in the round yellow-white lesions of the eyes compared with that in earlier stages. We have contacted with the patient for the follow-up OCT and FFA examinations a month later to check the possible structural changes of the macular area. LESSONS: The retina of a preterm infant is underdeveloped, we speculated that the bilateral retinal injuries in this baby could be caused by various factors.

Long noncoding RNA SNHG15 enhances the development of colorectal carcinoma via functioning as a ceRNA through miR-141/SIRT1/Wnt/ß-catenin axis.

Colon cancer, also known as colorectal carcinoma (CRC), remains to be one of the most mainsprings of cancer-produced deaths entire world. We planned to grab the role and possible biological cause of a long noncoding RNA, namely, small nucleolar RNA host gene 15 (SNHG15), in CRC. The mRNA level of SNHG15 in CRC tissues and cells was detected, followed by investigating the impacts of the depression of SNHG15 on CRC cell proliferation (viability and colony-forming), apoptosis, migration, and invasion. Moreover, the association between SNHG15 and miR-141 and the correlation between miR-141 and SIRT1 were also explored. Besides, the influences of dysregulated SNHG15 on the Wnt/ß-catenin signal-related proteins were determined. SNHG15 was highly expressed in CRC tissues and cells. Depression of SNHG15 depressed proliferation, enhanced apoptosis, and repressed the migration and invasion of CRC cells. In addition, SNHG15 presented a downside tendency on regulating miR-141, and the miR-141 inhibitor dramatically changeover the impacts of SNHG15 depression on tumor growth and metastasis. Moreover, SIRT1 was verified as a functional target of miR-141 in CRC cells. Besides, the suppression of SNHG15 remarkably controlled activating the Wnt/ß-catenin signals, which was reversed after inhibiting miR-141 at the same time. The investigated results in this research revealed that the increased expression of SNHG15 may enhance the process of CRC by acting as a ceRNA in regulating SIRT1 expression by sponging miR-141. Thus we propose that Wnt/ß-catenin signals may be a downriver regulator in mediating the impacts of SNHG15 in CRC and SNHG15-miR-141-SIRT1 axis may pave a new sight in explaining the biological processes of CRC.