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Background: The Lingqihuangban Granule (LQHBG), a remarkable Chinese herbal compound, has been used for decades to treat diabetic retinopathy (DR) in Department of Ophthalmology, Shanghai General Hospital (National Clinical Research Center for Eye Diseases) with obvious effects. Through the method of network pharmacology, the present study constructed bioactive component-relative targets and protein-protein interaction network of the LQHBG and implemented gene function analysis and pathway enrichment of targets, discussing the mechanisms of traditional Chinese medicine LQHBG in treating DR. Materials and Methods: The bioactive ingredients of LQHBG were screened and obtained using TCMSP and ETCM databases, while the potential targets of bioactive ingredients were predicted by SwissTargetPrediction and ETCM databases. Compared with the disease target databases of TTD, Drugbank, OMIM and DisGeNET, the therapeutic targets of LQHBG for DR were extracted. Based on DAVID platform, GO annotation and KEGG pathway analyses of key targets were explored, combined with the screening of core pathways on Omicshare database and pathway annotation on Reactome database. Results: A total of 357 bioactive components were screened from LQHBG, involving 86 possible targets of LQHBG treating DR. In PPI network, INS and ALB were identified as key genes. The effective targets were enriched in multiple signaling pathways, such as PI3K/Akt and MAPK pathways. Conclusion: This study revealed the possible targets and pathways of LQHBG treating DR, reflecting the characteristics of multicomponent, multitarget and multipathway treatment of a Chinese herbal compound, and provided new ideas for further discussion.

AimsTo investigate the associations of anthropometric indices, including body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), waist circumference (WC) and hip circumference (HC), with diabetic retinopathy (DR) and diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes mellitus (T2DM).Materials and methodsThis cross-sectional study evaluated 5226 participants with T2DM at Shanghai General Hospital between 2005 and 2016. Logistic regression models and restricted cubic spline analysis were used to assess the associations of anthropometric indices with DR and DKD.ResultsA BMI of around 25 kg/m2 was related to a low risk of DR (OR based on the third fifth: 0.752, 95%CI: 0.615-0.920). Besides, HC had an inverse association with DR in men independently of BMI (OR based on the highest fifth: 0.495, 95%CI: 0.350-0.697). In the restricted cubic spline models, BMI, WHtR, WC, and HC showed J-shaped associations with DKD, while WHR showed an S-shaped association with DKD. Compared to the lowest fifth, the odds ratios (OR) based on the highest fifth of BMI, WHR, WHtR, WC and HC for DKD were 1.927 (1.572-2.366), 1.566 (1.277-1.923), 1.91 (1.554-2.351), 1.91 (1.554-2.351) and 1.585 (1.300-1.937) respectively in multivariable models.ConclusionsA median BMI and a large hip might be related to a low risk of DR, while lower levels of all the anthropometric indices were associated with a lower risk of DKD. Our findings suggested maintain a median BMI, a low WHR, a low WHtR and a large hip for prevention of DR and DKD.

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.Retrospective cohort study.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.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.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.

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.

AimsTo determine the distribution of three different intraepithelial growth patterns (pagetoid, bowenoid and papillary) in eyelid sebaceous carcinoma (SC) and correlate them with the clinical characteristics and prognosis.MethodsA retrospective cohort study. The medical charts and pathological sections were retrospectively reviewed. All eligible patients were followed up for recurrence, metastasis and tumour-related mortality. The clinical significance of each intraepithelial growth pattern was determined by Cox regression.ResultsOf the 214 patients, 67 (31%) presented with intraepithelial invasion, among them, 34 (16%) were pagetoid, 27 (13%) were bowenoid and 6 (2.8%) were papillary. Patients of pagetoid intraepithelial spread showed significantly longer diagnostic delay (p=0.001) and more initial misdiagnoses of blepharitis (p=0.035). After a median follow-up period of 34.0 months, 67 (46%) patients in the non-intraepithelial group, 17 (50%) in the pagetoid group, 8 (30%) in the bowenoid group and 2 (33%) in the papillary group recurred. And 30 (20%) patients in the non-intraepithelial group, 9 (27%) in the pagetoid group and 4 (15%) in the bowenoid group developed metastasis. Moreover, 15 (10%) patients in the non-intraepithelial group, 6 (18%) in the pagetoid group and 1 (3.7%) in the bowenoid group died of SC. Cox regression indicated that pagetoid intraepithelial growth pattern was remarkably associated with increased chances of tumour-related mortality (HR=2.95, 95% CI 1.14 to 7.64, p=0.026).ConclusionsIntraepithelial tumour invasion was presented in nearly one third of patients with eyelid SC. Pagetoid intraepithelial neoplasia, the predominant growth pattern, significantly increased the risk of tumour-related mortality. Meticulous histopathological intraepithelial examination is recommended for every patient of eyelid SC. Special attention should be paid to those with pagetoid invasion, who may require more intensive managements.

Background Angiogenesis is an important parameter in the development of diabetic retinopathy (DR), and it is indicative of an early stage evolving into a late phase. Therefore, examining the role of angiogenic factors in early DR is crucial to understanding the mechanism of neovascularization. Methods The present study identified hub genes and pathways associated with angiogenesis in early DR using bioinformatics analysis. Genes from published literature and Gene Expression Omnibus (GEO) were collected and analysed. Results We collected 73 genes from 70 published studies in PubMed, which were referred to as DR-related gene set 1 (DRgset1). The gene expression profile of GSE12610 was downloaded, and 578 differentially expressed genes (DEGs) between diabetic and normal samples were identified. DEGs and DRgset1 were further combined to create DR-related gene set 2 (DRgset2). After an enrichment analysis, we identified 12 GO terms and 2 pathways associated with neovascularization in DRgset1, and 8 GO terms and 2 pathways in DRgset2. We found 39 new genes associated with angiogenesis and verified 8 candidate angiogenesis-related genes in DR cells using real-time PCR: PIK3CB, ALDH3A1, ITGA7, FGF23, THBS1, COL1A1, MAPK13, and AIF1. We identified 10 hub genes associated with neovascularization by constructing a protein-protein interaction (PPI) network: TNF, VEGFA, PIK3CB, TGFB1, EDN1, MMP9, TLR4, PDGFB, MMP2, and THBS1. Conclusions The present study analysed angiogenesis-related genes and pathways in early DR in a comprehensive and systematic manner. PIK3CB, ALDH3A1, ITGA7, FGF23, THBS1, COL1A1, MAPK13, and AIF1 may be the candidate genes to further explore the mechanisms of angiogenesis in early DR. TNF, PIK3CB, TGFB1, EDN1, MMP9, TLR4, PDGFB, MMP2, and THBS1 may be new targets for early neovascularization therapy in the future.

Cracks have a significant impact on the stability of rotating machinery. However, most studies focus on rotating machinery with only one crack. This paper discusses the influence of two cracks on the stability of a flywheel rotor-bearing system. In this study, the dynamic models of vertically placed flywheel rotor-bearing system with two open cracks and two breath cracks are established using the finite element method (FEM). Floquet theory is used to calculate the stability of the system and the influence of depth and positions of cracks are analyzed. The results show that breathing cracks cause more unstable regions than open cracks, and the range of rotating speeds over which the rotor is unstable increases with increasing crack depth. In addition, it is observed that when the crack locations are adjacent, the unstable region will become very large, covering most of the crack depth range and speed range, making the rotor extremely unstable. Besides, the bearing stiffness causes an offset in the unstable regions, whereas the damping influences the instability value of the rotor.

Histone deacetylase inhibitors (HDACis) have displayed neuroprotective effects in animal models of retinal ischemia/reperfusion (I/R) injury. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a redox-sensitive transcription factor responds to oxidative damage. We investigated the role of Nrf2 in retinal I/R injury, and further explored the mechanisms underlying Nrf2-mediated neuroprotection exerted by HDACi. High intraocular pressure was used to establish retinal I/R model in wild type (WT) and Nrf2 knockout (KO) mice. Nrf2 KO mice displayed more severe retinal damage after I/R. Trichostatin A (TSA) was administered to both WT and Nrf2 KO mice with retinal I/R damage. TSA significantly diminished the retinal ganglion cell degeneration in WT mice but offered no notable protection in Nrf2 KO mice. TSA markedly promoted Nrf2 nuclear translocation and its acetylation. In addition, TSA upregulated Nrf2 downstream proteins, such as Ho-1 and Nqo1, in retinal tissues. In the retinal neuronal cell line 661W, TSA reduced the expression of proinflammatory cytokines, Il-1β, Il-6, Tnf-α and Mmp-9, and it upregulated Bdnf under oxidative stress. However, this trend was not continued after silencing Nrf2. Chromatin immunoprecipitation assay demonstrated that Nrf2 at the Ho-1 promoter significantly increased transcriptional activity after oxidative stress induction. Nrf2, which is dispensable in HDACi-mediated neuroprotection, plays a major neuroprotective role in retinal I/R injury.

Uveal melanoma (UM) and retinoblastoma (RB), which cause blindness and even death, are the most frequently observed primary intraocular malignancies in adults and children, respectively. Epigenetic studies have shown that changes in the epigenome contribute to the rapid progression of both UM and RB following classic genetic changes. The loss of epigenetic homeostasis plays an important role in oncogenesis by disrupting the normal patterns of gene expression. The targetable nature of epigenetic modifications provides a unique opportunity to optimize treatment paradigms and establish new therapeutic options for both UM and RB with these aberrant epigenetic modifications. We aimed to review the research findings regarding relevant epigenetic changes in UM and RB. Herein, we 1) summarize the literature, with an emphasis on epigenetic alterations, including DNA methylation, histone modifications, RNA modifications, noncoding RNAs and an abnormal chromosomal architecture; 2) elaborate on the regulatory role of epigenetic modifications in biological processes during tumorigenesis; and 3) propose promising therapeutic candidates for epigenetic targets and update the list of epigenetic drugs for the treatment of UM and RB. In summary, we endeavour to depict the epigenetic landscape of primary intraocular malignancy tumorigenesis and provide potential epigenetic targets in the treatment of these tumours.

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.Retrospective cohort study covering all 31 provinces (38 retinoblastoma treating centers) of mainland China.One thousand six hundred seventy-eight patients diagnosed with group D or E retinoblastoma from January 2006 through May 2016.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.Overall survival and final eye preservation.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.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.

Microvascular dysfunction is the primary aetiology of visual impairment caused by diabetic retinopathy (DR). Dihydroartemisinin (DHA), the active metabolite of the antimalarials artemisinins, exhibits antiangiogenic properties in numerous diseases. Here, we investigated the function and mechanisms of DHA as a vasculoprotective agent in DR. DHA exerted its protective effect on vascular injuries in diabetic mice and inhibited cell proliferation and tube formation in human retinal microvascular endothelial cells by decreasing the level of fatty acid synthase (FASN), enhancing the malonylation of mechanistic target of rapamycin (mTOR) at lysine 1218 (K1218) and attenuating the activation of mTOR complex 1 (mTORC1). Impressively, a chemosynthetic small interfering RNA against FASN and mutagenesis of K1218 of mTOR showed therapeutic potential in suppressing cell proliferation and tube formation induced by high glucose. Notably, suppression of mTORC1 kinase activity further inhibited FASN by reducing p70S6K phosphorylation to subsequently reduce the expression of sterol regulatory element binding protein 1, which interacted directly with the FASN promoter at nucleotide positions −64 and −55. In conclusion, our study elucidated the promising effects of FASN and malonylation on vascular injuries of DR and indicated the great potential of DHA as a therapeutic approach.

Objective An elevated serum calcium level is associated with a higher risk of type 2 diabetes (T2D), but its role in microvascular complications remains unclear. This study was conducted to investigate the association between serum calcium levels and vision-threatening diabetic retinopathy (VTDR). Methods This study employed a cross-sectional and longitudinal design. The cross-sectional part included all patients treated for T2D at Shanghai General Hospital between 2007 and 2016, while the longitudinal part involved an overlapping cohort of diabetic patients without VTDR who were followed from their admission until December 2019. Multivariable logistic and Cox proportional hazard regression analyses were performed, respectively. VTDR was defined as severe nonproliferative diabetic retinopathy, proliferative diabetic retinopathy, or clinically significant macular edema. Results A total of 3269 patients were included in the cross-sectional analysis, and 649 patients were included in the longitudinal analysis. In the cross-sectional analysis, higher corrected serum calcium (odds ratio: 1.31 per 0.1 mmol/L, 95% confidence interval: 1.16-1.49), younger age, longer diabetes duration, albuminuria, impaired renal function, and lower serum magnesium were independently associated with VTDR. In the longitudinal analysis, 95 subjects developed VTDR during follow-up (9.7 years, interquartile range: 7.4-10.9 years). Higher corrected serum calcium (hazard ratio: 1.38 per 0.1 mmol/L, 95% confidence interval: 1.10-1.72), younger age, longer diabetes duration, sub-VTDR, albuminuria, lower serum magnesium, and higher glycated hemoglobin were identified as independent risk factors for VTDR. Conclusions A higher serum calcium level may be an independent risk factor for VTDR in patients with T2D.

BackgroundLong non-coding RNAs (lncRNAs) have been identified as important epigenetic regulators that play critical roles in human cancers. However, the regulatory functions of lncRNAs in tumorigenesis remains to be elucidated. Here, we aimed to investigate the molecular mechanisms and potential clinical application of a novel lncRNA, retinoblastoma associated transcript-1 (RBAT1), in tumorigenesis.MethodsRBAT1 expression was determined by real-time PCR in both retinoblastoma (Rb) and bladder cancer (BCa) cell lines and clinical tissues. Chromatin isolation using RNA purification (ChIRP) assays were performed to identify RBAT1-interacting proteins. Patient-derived xenograft (PDX) retinoblastoma models were established to test the therapeutic potential of RBAT1-targeting GapmeRs.ResultsHere, we found that RBAT1 expression was significantly higher in Rb and BCa tissues than that in adjacent tissues. Functional assays revealed that RBAT1 accelerated tumorigenesis both in vitro and in vivo.Mechanistically, RBAT1 recruited HNRNPL protein to E2F3 promoter, thereby activating E2F3 transcription. Therapeutically, GapmeR-mediated RBAT1 silencing significantly inhibited tumorigenesis in orthotopic xenograft retinoblastoma models derived from Rb cell lines and Rb primary cells.ConclusionsRBAT1 overexpression upregulates a known oncogene, E2F3, via directly recruiting HNPNPL to its promoter and cis-activating its expression. Our finding provides a novel mechanism of lncRNA biology and provides potential targets for diagnosis and treatment of Rb and BCa.

Background: LingqiHuangban Granule(LQHBG) is a famous traditional Chinese medicine formula used to manage retinal diseases, as an effective holistic treatment through warming Yang to exert tonifying effects on kidney and invigorating spleen to remove dampness to nourish essence of effect. The study examined protection of LQHBG on oxidative stress-induced injury in human retinal endothelial cells(HRECs) in vitro, determined the potential molecular targets of LQHBG using network pharmacology.Methods: The potential targets of active ingredients in LQHBG were predicted using pharmmapper. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were carried out using Molecule Annotation System. The protein-protein interaction networks were constructed using Cytoscape. LQHBG was administered to rabbits to prepare medicated serum. The apoptosis of HRECs was evaluated by TUNEL and Flow Cytometry(FCM). MDA, SOD, LDH, GSH-Px, and T-AOC were detected. The mRNA expressions of Nrf2, NF-κB and HO-1 were detected, protein expression levels of Nrf2, Bcl-2, NF-κB, HO-1 and caspase-3 were analyzed.Results: TUNEL demonstrated the numbers of apoptotic cells in low-and high-dose LQHBG groups was obviously less than model group(PConclusion: LQHBG protected HRECs against oxidative-stress via suppression of apoptosis and elevation of antioxidant ability, which may involve activation of Nrf2/ARE/HO-1 pathway and inhibition of NF-κB pathway.

High-altitude retinopathy (HAR) is an ocular manifestation of acute oxygen deficiency at high altitudes. Although the pathophysiology of HAR has been revealed by many studies in recent years, the molecular mechanism is not yet clear. Our study aimed to systematically identify the genes and microRNA (miRNA) and explore the potential biomarkers associated with HAR by integrated bioinformatics analysis. The mRNA and miRNA expression profiles were obtained from the Gene Expression Omnibus database. We performed Gene Ontology functional annotations and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Potential target gene analysis and miRNA–mRNA network analysis were also conducted. Quantitative RT-PCR (qRT-PCR) was used to validate the results of the bioinformatics analysis. Through a series of bioinformatics analyses and experiments, we selected 16 differentially expressed miRNAs (DE-miRNAs) and 157 differentially expressed genes related to acute mountain sickness (AMS) and constructed a miRNA–mRNA network containing 240 relationship pairs. The hub genes were filtered from the protein-protein interaction network: IL7R, FOS, IL10, FCGR2A, DDX3X, CDK1, BCL11B and HNRNPH1, which were all down-regulated in the AMS group. Then, nine up-regulated DE-miRNAs and eight hub genes were verified by qRT-PCR in our hypoxia-induced HAR cell model. The expression of miR-3177-3p, miR-369-3p, miR-603, miR-495, miR-4791, miR-424-5p, FOS, IL10 and IL7R was consistent with our bioinformatics results. In conclusion, FOS, IL10, IL-7R and 7 DE-miRNAs may participate in the development of HAR. Our findings will contribute to the identification of biomarkers and promote the effective prevention and treatment of HAR in the future.

Purpose. To assess the quality of life (QoL) and the long-term psychosocial outcomes in adult survivors of unilateral retinoblastoma (RB). Methods. This is a cross-sectional study. Enrolment was offered to all adult survivors of unilateral RB who were treated by enucleation and were followed up in the Ninth People’s Hospital of Shanghai Jiao Tong University School of Medicine; noncancer healthy adults served as a control group. All participants completed a series of questionnaires consisting of two aspects, QoL and psychosocial status. The psychosocial outcomes included anxiety, depression, fear of cancer, and satisfaction with facial appearance. Results. A total of 66 RB survivors (43.0% male) and 66 healthy adults (33.3% male) were aged 27.94 ± 7.63 and 29.18 ± 8.37 at the time of the study, respectively. Adult RB survivors did not have significantly higher rates of depression and anxiety compared with the control group, and they experienced a relatively good QoL. RB survivors were more likely to worry about their facial appearance (median, 1.59 [inter-quartile range, IQR, 1.27 to 2.16] v median, 0.36 [IQR, 0.09 to 1.18]; p<0.001). Radiotherapy was not the factor affecting satisfaction with facial appearance (β, −0.27 [confidence interval, CI, −0.69 to 0.16]; p=0.214). Females were more likely to be influenced by the disease (mean, 29.59 ± 8.89 v mean, 24.37 ± 6.92; p=0.031) and worry about their appearance (mean, 1.88 ± 0.84 v mean, 1.46 ± 0.77; p=0.041). Conclusions. Unilateral RB survivors are a fairly healthy and resilient group. Most unilateral RB survivors experience a relatively good QoL, and they do not have poorer psychosocial functioning compared with a noncancer sample. Females may need more specific psychosocial care.

Background NUT midline carcinoma (NMC) is a poorly differentiated squamous cancer with a median survival at less than 7 months. NMC is resistant to conventional chemotherapies and characterized by rearrangement of the NUT gene. Case presentation Here, we described a patient who initially presented with epiphora, and an orbit involved NMC. In addition, we for the first time demonstrated that local radiotherapy combined with tyrosine kinase inhibitor (TKI) could significantly inhibit tumor progression in orbital involvement by NMC. Conclusions Our study for the first time described an orbit involved NMC patient initially presented with epiphora. In addition, we provided an alternative to the management of orbit involved NMC.

Transmission towers are structurally complex, which makes it challenging to choose the right place and number of sensors for health monitoring. In this paper, optimal sensor placement of a cat-head-type transmission tower is conducted by using the Effective Independent Method (EIM) and a method is proposed for calculating the minimum number of sensors for structural health monitoring by combining EIM and Modal Assurance Criterion (MAC). The method for calculating the number of sensors prescribed in this paper derives a curve that shows the relationship between MAC value and the number of sensors. It is found that the MAC value decreases with increase in the number of sensors. When the number of sensors reaches a certain threshold, the curve tends to stabilize. Then, the number of sensors corresponding to the minimum MAC is proposed as the minimum number of sensors. Through calculation, the minimum number of sensors of the cat-head-type transmission tower is obtained. Also, the optimal sensor placement results show that the position of a large number of sensors includes the position of a smaller number of sensors.

Additional file 1: Supplementary Table 1. Clinicopathological features and demographics of retinoblastoma (Rb) patient cohorts. Supplementary Table 2. Clinicopathological features of Bladder Urothelial Carcinoma (BCa) patient cohorts. Supplementary Table 3. Primers, oligos, shRNAs, GapmeRs and probes used in the experiment. Supplementary Table 4. The list of lncRNAs that shared an overlap region with tumor related genes in retinoblastoma. Supplementary Table 5. Interactions between E2F3 and its targeting genes. Supplementary Table 6. Information of GO (Biological Process) Enrichment Analysis. Supplementary Table 7. ChIRP-MS identified lncRNA RBAT1 specifically binding proteins in Y79. Supplementary Table 8. ChIRP-MS identified lncRNA RBAT1 specifically binding proteins in 5637. Fig. S1. RBAT1 is a novel transcript in retinoblastoma (Rb) and bladder cancer (BCa). (A) Volcano plots of differentially expressed protein-coding genes. X axis represents log fold changes. Y axis represents log p values. Blue points denote significantly downregulated genes and red points denote significantly upregulated genes. (B) Agarose gel electrophoresis of PCR products generated by 3′ (left) and 5′ (right) RACE. (C) Schematic diagram of RACE assay. Fig. S2. RACE and coding potential analyses of RBAT1. (A) The full sequence of RBAT1. (B) Coding Potential Calculator (CPC) analysis suggested that RBAT1 is a noncoding RNA. GAPDH, CRTC1 and ACTB genes were used as protein-coding controls. XIST and HOTAIR genes were used as noncoding RNA controls. (C) RBAT1 was predicted by PhyloCSF to have no protein coding potential. The peaks showed the PhyloCSF score for each codon in each of 6 frames. Regions with a score less than 0 are predicted to be noncoding while Regions with a score greater than 0 are predicted to be coding. The protein coding gene ACTB and the noncoding RNA gene HOTAIR were used as controls. (D) Fractionation of tumor cell lines (Y79, WERI-Rb-1 and 5637) followed by RT-PCR. RBAT1 was mainly expressed in the nucleus. GAPDH and U6 RNA served as positive controls for the cytoplasmic and nuclear fractions, respectively. Fig. S3. Effect of RBAT1 on colony formation ability and migration ability of tumor cell lines. (A) A colony formation assay was performed to determine the colony formation ability of RBAT1-silenced tumor cell lines (Y79, WERI-Rb-1 and 5637). For colony formation assays, 500 cells were seeded in 6-well plates (Poly-L-lysine-coated 6-well plates for retinoblastoma cell lines). 7–14 days later, the colonies were washed with PBS, fixed and stained for 20 min with a 1% crystal violet solution. Images were captured by a scanner, and the percentage of cell occupancy was counted and analyzed by ImageJ software. (B) The migration and invasion abilities displayed no significant changes in RBAT1-silenced tumor cell lines (5637) compared with ctrl group. (C) A colony formation assay was performed to test sustained effect after removing GapmeRs at the 3rd day. (D) A real-time PCR was performed to determine the expression level of RBAT1 in tumors from GapmeR1/2 treated groups and Ctrl. The results are shown as the mean ± SD in three independent experiments. *p

Additional file 2: Table S2. Genes associated with early DR in literature (DRgset1).

Additional file 3: Table S3. DEGs associated with early DR from GSE12610.

Background The prognosis of Chinese patients with eyelid sebaceous carcinoma (SC) has not been updated for >3 decades. The prognostic predictors are multifactorial, and there is no validated prognostic model for eyelid SC. Methods This study included 238 consecutive patients with eyelid SC. All eligible patients were followed up for metastasis and mortality. The predictors of tumor-related survival were explored by Cox analyses. A prognostic nomogram was developed and validated using bootstrap resampling. The predictive accuracy and discriminative ability were compared between the nomogram and the Tumor, Node, Metastasis (TNM) staging system. Findings After a median follow-up period of 55.5 months, 27 (11.3%) patients died of metastatic SC, with a median survival time of 48.0 months. The 5-year and 10-year tumor-related survival rates were 88.1% and 77.9%, respectively. Orbital involvement (HR: 3.11, p = .022), the greatest tumor basal diameter (HR: 1.06, p = .003), the presence of pagetoid spread (HR: 2.90, p = .017), and having lymph node metastasis at initial diagnosis (HR: 13.66, p

Aberrant chromatin transformation dysregulates gene expression and may be an important driver of tumorigenesis. However, the functional role of chromosomal dynamics in tumorigenesis remains to be elucidated. Here, using in vitro and in vivo experiments, we reveal a novel long noncoding (lncing) driver at chr12p13.3, in which a novel lncRNA GALNT8 Antisense Upstream 1 (GAU1) is initially activated by an open chromatin status, triggering recruitment of the transcription elongation factor TCEA1 at the oncogene GALNT8 promoter and cis-activates the expression of GALNT8. Analysis of The Cancer Genome Atlas (TCGA) clinical database revealed that the GAU1/GALNT8 driver serves as an important indicative biomarker, and targeted silencing of GAU1 via the HKP-encapsulated method exhibited therapeutic efficacy in orthotopic xenografts. Our study presents a novel oncogenetic mechanism in which aberrant tuning of the chromatin state at specific chromosomal loci exposes factor-binding sites, leading to recruitment of trans-factor and activation of oncogenetic driver, thereby provide a novel alternative concept of chromatin dynamics in tumorigenesis.

The purpose of this study is to compare the efficacy of intraoperative 360° and localized laser retinopexy in 23-gauge pars plana vitrectomy (PPV) for rhegmatogenous retinal detachments (RRD) with undetected retinal breaks intraoperatively. This is a retrospective, comparative, interventional study. Medical records of 48 consecutive eyes with RRD of intraoperative undetected retinal breaks were reviewed. Nineteen patients (group I) received 360° laser retinopexy in PPV, while the remaining 29 patients (group II) underwent localized laser retinopexy. In group I, a triple row of confluent medium-white laser burns were placed posterior to the ora serrata. Anatomical and visual outcomes of the two groups were compared. The mean follow-up period was 13.46 ± 3.02 months. No significant difference was identified in baseline characteristics. A single-operation reattachment rate of 89.47% was achieved in group I, which was significantly higher than that of group II (55.17%, p = 0.01), and this trend was not weakened after adjustment for the confounding factor (odds ratio 0.15, p = 0.03). Moreover, greater improvement of postoperative best-corrected visual acuity was observed in group I. Significant complications sufficient to require further operation included proliferative vitreoretinopathy in 2 (4.17%) eyes and epiretinal membrane in 4 (8.33%) eyes. Three hundred sixty-degree laser retinopexy was associated with better anatomic and visual outcomes in RRD patients with unseen breaks intraoperatively, when compared with localized laser retinopexy in PPV.

PURPOSE To compare structural and functional improvements in patients with vitreous haemorrhage (VH) with different IOPs re-established at the end of pars plana vitrectomy (PPV). METHODS It is a prospective, randomized, comparative, interventional study. Ninety-five patients with nonclearing VH were randomized to receive PPV with normalized IOPs of 15 mmHg (Group I: 32 eyes), 25 mmHg (Group II: 32 eyes) and 35 mmHg (Group III: 31 eyes) at the end of surgery. The grade of vitreous opacity and best-corrected visual acuity (BCVA) on postoperative day 1, week 1, month 1 and month 3 were compared with a mixed model for repeated measures analysis. RESULTS All 3 groups achieved significant improvement on postoperatively in BCVA (p