Low expression of NR1D1 and NR2E3 is associated with advanced features of retinoblastoma.

PURPOSE: To investigate the expression of nuclear receptor subfamily 1 group D member 1 (NR1D1) and nuclear receptor subfamily 2 group E Member 3 (NR2E3) in retinoblastoma (RB) and their correlation with the clinical and pathological features of RB. METHODS: Immunohistochemical (IHC) assays were performed to detect and evaluate the expression levels of NR1D1 and NR2E3 in paraffin-embedded tissue samples. The relationship between the expression levels and clinicopathological characteristics of RB patients was analyzed using the χ2 test or Fisher exact test. RESULTS: A total of 51 RB patients were involved in this research. The expression levels of NR1D1 (P = 0.004) and NR2E3 (P = 0.024) were significantly lower in RB tumor tissues than in normal retina. The expression levels of NR1D1 and NR2E3 were less positive in RB patients with advanced stages (P = 0.007, P = 0.015), choroidal infiltration (P = 0.003, P = 0.029), and optic nerve infiltration (P = 0.036, P = 0.003). In addition, a low expression level of NR2E3 was associated with high-risk pathology (P = 0.025) and necrosis (P = 0.035) of RB tissues. CONCLUSION: The expression levels of NR1D1 and NR2E3 were decreased in RB and closely associated with the clinical stage and high invasion of the disease. These findings provide new insights into the mechanism of RB progression and suggest that NR1D1 and NR2E3 could be potential targets for treatment strategies.

Acute spontaneous vortex vein occlusion: clinical features, multimodal imaging and natural course.

AIMS: To describe the clinical features, multimodal imaging, treatments and natural course of acute spontaneous vortex vein occlusion. METHODS: Clinical data were collected on nine patients with acute vortex vein occlusion. The symptoms and signs, multimodal imaging, treatments and follow-up results were summarised. RESULTS: Six patients (66.7%) were men and three (33.3%) were women. The mean age was 47.8±15.4 years. Patients were initially misdiagnosed as having choroidal tumour (66.7%), scleritis (22.2%) and peripheral exudative haemorrhagic chorioretinopathy (11.1%). The related clinical characteristics included choroidal pseudo-tumour (100%), anterior segment injection (88.9%), acute ocular pain (77.8%), transient blurred vision (66.7%) and subsequent scleral icterus (66.7%). Six patients (66.7%) experienced a definite Valsalva manoeuvre prior to the onset. In acute phase, ultrasonography showed a low-to-medium reflective lesion without inside blood flow signal (mean thickness, 2.7±0.6 mm). Swept-source optical coherence tomography angiography (SS-OCTA) demonstrated the dilated vortex veins and ampulla with suprachoroidal haemorrhage and exudation. Indocyanine green angiography (ICGA) demonstrated choroidal circulation abnormalities in the affected quadrant. MRI showed a well-defined mass with enhancement. The main treatment was medical observation (44.5%). The choroidal pseudo-tumour spontaneously resolved with a mean course of 4.1±1.9 weeks. CONCLUSIONS: Acute vortex vein occlusion is a rare condition and initial misdiagnosis is not uncommon. It is mainly identified as an evanescent choroidal pseudo-tumour with acute pain, red eye and blurred vision. Widefield ICGA and SS-OCTA can offer valuable diagnostic clues. Medical observation may be a treatment option.

STING promotes invasion and migration of uveal melanoma through p38­MAPK signaling.

Uveal melanoma (UM) is the most common intraocular malignant tumor in adults, with a lack of effective treatment for metastasis and a poor prognosis. Stimulator of interferon genes (STING, also known as TMEM173) plays an important role in tumor development by regulating cell proliferation, metastasis and other cellular processes. However, the function of STING in UM remains unclear and requires further investigation. The present study analyzed the expression status of STING to elucidate the mechanisms underlying UM. The correlation between STING and the prognosis of UM was evaluated based on UM RNA­seq data and clinical information extracted from The Cancer Genome Atlas database. Quantification of STING in UM cell lines and tissues was performed using the Wes Separation protein immunoassay. The effects of STING on the proliferation, migration and invasion of UM cells were investigated using Cell Counting Kit­8, Transwell and wound healing experiments. Survival analysis demonstrated that high levels of STING in UM tissues indicated a poor prognosis. The expression of STING in UM tissues was higher than that in the choroid membranes. Furthermore, it was found that downregulation of STING expression in UM cells suppressed migration and invasion, whereas overexpression of STING significantly promoted migration and invasion. Notably, STING had no significant effect on UM cell proliferation. It was also identified that STING positively upregulated the phosphorylation of p38 mitogen­activated protein kinase (p38­MAPK) in UM cells, enhancing cell migration and invasion, which the p38­MAPK inhibitor SB203580 reversed. Finally, the results of the present study demonstrated that high STING expression in UM indicates a poor prognosis. STING was revealed to promote the migration and invasion of UM cells through p38­MAPK signaling.

Gut Microbiome-Generated Phenylacetylglutamine from Dietary Protein is Associated with Crohn's Disease and Exacerbates Colitis in Mouse Model Possibly via Platelet Activation.

OBJECTIVES: Our aims were to better understand the interplay of diet and gut microbiota in Crohn's disease [CD], taking advantage of a new-onset treatment-naïve CD cohort. We focus on phenylacetylglutamine [PAGln], a diet-derived meta-organismal prothrombotic metabolite. DESIGN: We collected faecal and serum samples from a CD cohort [n = 136] and healthy controls [n = 126] prior to treatment, and quantified serum PAGln using LC-MS/MS. Diet was assessed using food-frequency questionnaires. Mice [C57BL/6] were fed high/low-protein diets and administered dextran sodium sulphate [DSS] to examine plasma PAGly, thrombosis potential, and colitis severity. PAGly or saline was administered to DSS-induced colitis mice, and colitis severity and colonic tissue gene expression were examined. P-selectin and CD40L expression were determined in human platelet-rich plasma [n = 5-6] after exposure to platelet agonists following PAGln priming. Bioinformatic analysis and bacterial culturing identified the main contributor of PAGln in CD. RESULTS: PAGln, a meta-organismal prothrombotic metabolite, is associated with CD. Administration of PAGly exacerbated colitis in a mouse model and upregulated coagulation-related biological processes. Antiplatelet medicine, dipyridamole, attenuated PAGly-enhanced colitis susceptibility. PAGln enhanced platelet activation and CD40L expression in platelet-rich plasma ex vivo. Further study revealed that high dietary protein intake and increased abundance of phenylacetic acid [PAA]-producing Proteobacteria mediated by phenylpyruvate decarboxylase act in concert to cause the elevated PAGln levels in CD patients. CONCLUSION: Taken together, ppdc-carrying Proteobacteria-generated PAGln from dietary protein is associated with CD and exacerbates colitis possibly via platelet-induced coagulation and inflammation These results suggest that PAGln is a potential early diagnostic marker and therapeutic target of CD.

Oxidative stress gene expression, DNA methylation, and gut microbiota interaction trigger Crohn's disease: a multi-omics Mendelian randomization study.

BACKGROUND: Oxidative stress (OS) is a key pathophysiological mechanism in Crohn's disease (CD). OS-related genes can be affected by environmental factors, intestinal inflammation, gut microbiota, and epigenetic changes. However, the role of OS as a potential CD etiological factor or triggering factor is unknown, as differentially expressed OS genes in CD can be either a cause or a subsequent change of intestinal inflammation. Herein, we used a multi-omics summary data-based Mendelian randomization (SMR) approach to identify putative causal effects and underlying mechanisms of OS genes in CD. METHODS: OS-related genes were extracted from the GeneCards database. Intestinal transcriptome datasets were collected from the Gene Expression Omnibus (GEO) database and meta-analyzed to identify differentially expressed genes (DEGs) related to OS in CD. Integration analyses of the largest CD genome-wide association study (GWAS) summaries with expression quantitative trait loci (eQTLs) and DNA methylation QTLs (mQTLs) from the blood were performed using SMR methods to prioritize putative blood OS genes and their regulatory elements associated with CD risk. Up-to-date intestinal eQTLs and fecal microbial QTLs (mbQTLs) were integrated to uncover potential interactions between host OS gene expression and gut microbiota through SMR and colocalization analysis. Two additional Mendelian randomization (MR) methods were used as sensitivity analyses. Putative results were validated in an independent multi-omics cohort from the First Affiliated Hospital of Sun Yat-sen University (FAH-SYS). RESULTS: A meta-analysis from six datasets identified 438 OS-related DEGs enriched in intestinal enterocytes in CD from 817 OS-related genes. Five genes from blood tissue were prioritized as candidate CD-causal genes using three-step SMR methods: BAD, SHC1, STAT3, MUC1, and GPX3. Furthermore, SMR analysis also identified five putative intestinal genes, three of which were involved in gene-microbiota interactions through colocalization analysis: MUC1, CD40, and PRKAB1. Validation results showed that 88.79% of DEGs were replicated in the FAH-SYS cohort. Associations between pairs of MUC1-Bacillus aciditolerans and PRKAB1-Escherichia coli in the FAH-SYS cohort were consistent with eQTL-mbQTL colocalization. CONCLUSIONS: This multi-omics integration study highlighted that OS genes causal to CD are regulated by DNA methylation and host-microbiota interactions. This provides evidence for future targeted functional research aimed at developing suitable therapeutic interventions and disease prevention.

A Novel Serum Metabolomic Panel for the Diagnosis of Crohn's Disease.

BACKGROUND: A distinctive metabolic phenotype provides the opportunity to discover noninvasive biomarkers for the diagnosis of Crohn's disease (CD) and for differentiating it from other intestinal inflammatory diseases. The study sought to identify new biomarkers for CD diagnosis. METHODS: Serum metabolites from 68 newly diagnosed and treatment-naïve patients with CD and 56 healthy control (HC) subjects were profiled using targeted liquid chromatography-mass spectrometry. Five metabolic biomarkers were identified to distinguish patients with CD from the HC subjects and validated in a separate cohort consisting of 110 patients with CD and 90 HC subjects using a combination of univariate analysis, orthogonal partial least-squares discriminant analysis, and receiver-operating characteristic curve analysis. Differences in the 5 metabolites were evaluated among patients with CD and patients with ulcerative colitis (n = 62), intestinal tuberculosis (n = 48), and Behçet's disease (n = 31). RESULTS: Among the 185 quantified metabolites, a panel of 5 (pyruvate, phenylacetylglutamine, isolithocholic acid, taurodeoxycholic acid, and glycolithocholic acid) were found to distinguish patients with CD with high accuracy from HC subjects, with an area under the curve of 0.861 (P < .001). The performance of the model in assessing clinical disease activity was comparable to that of the present biomarkers: C-reactive protein and erythrocyte sedimentation rate. The 5 metabolites were significantly different among the patients and were valuable in the differentiation between CD and other chronic intestinal inflammatory diseases. CONCLUSIONS: The combination of 5 serum metabolite biomarkers for the diagnosis of CD has the potential to provide an accurate, noninvasive, and inexpensive alternative to conventional tests and might be valuable for the differentiation from other diagnostically challenging intestinal inflammatory diseases.

Serum metabolomic analysis was performed on patients with Crohn's disease and healthy control subjects, which discovered 5 metabolites as a novel serum metabolomic panel. These metabolites were further validated in a second patient cohort and a third differentiation cohort. The data showed that these metabolites were valuable in diagnosis of Crohn's disease and for differentiating it from other intestinal inflammatory diseases.

Adjuvant therapy for orbital non-rhabdomyosarcoma soft tissue sarcoma: comparison of long-term outcome between radiotherapy and chemotherapy.

AIM: To illustrate clinicopathological features of orbital non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), and to compare the treatment outcome between postoperative radiotherapy (RT) and chemotherapy in a retrospective analysis nearly 20y. METHODS: A retrospective cohort study of 56 patients with orbital NRSTS were reviewed, 34 of whom received postoperative RT, and 22 received postoperative chemotherapy. The clinicopathological features, local recurrence, metastases, and survival data were recorded. Survival analysis was performed using the Kaplan-Meier method. RESULTS: During follow-up (111.8mo, ranged 8-233mo) for 56 patients, 19 patients of them developed local recurrence, and 7 patients developed distant metastases. Fifteen patients died during follow-up period. Overall survival rates considering the whole study group was 78.57% at 5y, and 72.16% at 10y after the initial diagnosis. Compared with chemotherapy, RT was associated with lower risk of local recurrence [hazard ratio for RT vs chemotherapy, 0.263, 95% confidence interval (CI), 0.095-0.728, P=0.0015]; with lower risk of distant metastasis (hazard ratio for RT vs chemotherapy, 0.073, 95%CI, 0.015-0.364, P=0.0014); and with lower risk of death from disease (hazard ratio for RT vs chemotherapy, 0.066, 95%CI, 0.022-0.200, P<0.0001). The 5-year survival rate in RT group was 97.06% compared to 50% in chemotherapy group. CONCLUSION: In patients with orbital NRSTS, postoperative RT provides better control of local recurrence, distant metastasis, and death from disease than chemotherapy. RT is the more preferrable adjuvant therapy compared to chemotherapy possibly.

Identification of non-coding RNAs and their functional network associated with optic nerve invasion in retinoblastoma.

Optic nerve invasion (ONI) is an important high-risk feature and prognostic indicator of retinoblastoma (RB). Emerging evidence has revealed that non-coding RNAs (ncRNAs) play important roles in tumor perineural invasion (PNI). Nevertheless, the regulatory role of ncRNAs in the ONI of RB is poorly understood. In the current study, whole-transcriptome sequencing was performed to assess the expression profiles of ncRNAs and mRNAs in RB tissues, with or without ONI. Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, we predicted the biological functions of differentially expressed (DE) mRNAs. We then constructed competing endogenous RNA (ceRNA) regulatory networks based on bioinformatics analysis. The hsa_circ_0015965/lncRNA MEG3-hsa-miR-378a-5p-NOTCH1 pathway was selected and validated by real-time qPCR, western blotting, and dual luciferase reporter assays. Moreover, we demonstrated that NOTCH1 promotes the malignant progression of RB. Taken together, our results provide novel insights into the mechanism underlying optic nerve invasion in RB.

Changes in retinal nerve fibre layer, ganglion cell layer and visual function in eyes with thyroid eye disease of different severities with and without orbital decompression.

PURPOSE: To evaluate progressive changes in retinal nerve fibre layer (RNFL), ganglion cell layer/inner plexiform layer (GCL/IPL) and visual function in thyroid eye disease (TED) patients with and without orbital decompression. METHODS: Sixty TED patients (105 eyes) were included. All patients were divided into mild, moderate-to-severe and dysthyroid optic neuropathy (DON) groups. Orbital decompression was performed in the moderate-to-severe and DON groups. Optic coherence tomography (OCT), visual field (VF) and best-corrected visual acuity (BCVA) were performed pre- and postoperatively. Preoperative follow-up was performed in the mild group and in part of the moderate-to-severe and DON groups. RESULTS: After decompression, the thickness of GCL/IPL and RNFL significantly decreased in DON group (p < 0.05), with varying degrees of decrease in eyes with optic disc swelling, atrophy and normal appearance. The mean GCL/IPL thickness significantly decreased in moderate-to-severe group (p < 0.05), the mean RNFL thickness slightly decreased with no statistical significance (p = 0.07). During the preoperative follow-ups, the mean GCL/IPL thickness significantly decreased (p = 0.04), whereas the mean RNFL thickness tended to increase (p = 0.13) in DON group. The thickness of GCL/IPL and RNFL did not change significantly in the mild and moderate-to-severe groups (p > 0.05). BCVA and VF did not change significantly in any group (p > 0.05) preoperatively. CONCLUSION: Swelling and degeneration of retinal ganglion cells (RGCs) may coexist in DON eyes, leading to continuous changes in the RNFL and GCL/IPL thickness either before or after decompression. Slight swelling and degeneration of RGCs may exist in moderate-to-severe TED eyes, although OCT measurements and visual functions remain stable before surgery.

Dietary inflammatory potential mediated gut microbiota and metabolite alterations in Crohn's disease: A fire-new perspective.

BACKGROUND & AIMS: Pro-inflammatory diet interacting with gut microbiome might trigger for Crohn's disease (CD). We aimed to investigate the relationship between dietary inflammatory potential and microflora/metabolites change and their link with CD. METHODS: The dietary inflammatory potential was assessed using a dietary inflammatory index (DII) based on the Food Frequency Questionnaire from 150 new-onset CD patients and 285 healthy controls (HCs). We selected 41 CD patients and 89 HCs who had not received medication for metagenomic and targeted metabolomic sequencing to profile their gut microbial composition as well as fecal and serum metabolites. DII scores were classified into quartiles to investigate associations among different variables. RESULTS: DII scores of CD patients were significantly higher than HCs (0.56 ± 1.20 vs 0.23 ± 1.02, p = 0.017). With adjustment for confounders, a higher DII score was significantly associated with higher risk of CD (OR: 1.420; 95% CI: 1.049, 1.923, p = 0.023). DII score also was positively correlated with disease activity (p = 0.001). Morganella morganii and Veillonella parvula were increased while Coprococcus eutactus was decreased in the pro-inflammatory diets group, as well as in CD. DII-related bacteria were associated with disease activity and inflammatory markers in CD patients. Among the metabolic change, pro-inflammatory diet induced metabolites change were largely involved in amino acid metabolic pathways that were also observed in CD. CONCLUSIONS: Pro-inflammatory diet might be associated with increased risk and disease activity of CD. Diet with high DII potentially involves in CD by mediating alterations in gut microbiota and metabolites.

Insights Into Ferroptosis: Targeting Glycolysis to Treat Graves' Orbitopathy.

CONTEXT: Oxidative stress plays an indispensable role in pathogenesis of Graves' orbitopathy (GO). Ferroptosis is a newly discovered form of cell death resulting from lipid peroxidation. Little is known about the role of ferroptosis in GO. OBJECTIVE: We aimed to identify the divergent role of ferroptosis in the GO and control orbital fibroblasts (OFs). METHODS: Orbital fat/connective tissues and serum immunoglobulins (Igs) were collected from GO and control subjects. Cell viability and lipid peroxidation were measured to evaluate ferroptosis sensitivity. Pyruvate dehydrogenase kinase 2 (PDK2) level and oxygen consumption rate were quantified to assess glycolysis status. RESULTS: Primary OFs were cultured from orbital tissues. Ferroptosis was induced by cystine deprivation and/or erastin treatment. The GO OFs possessed stronger resistance to ferroptosis than the control OFs. Selenium, a potential ferroptosis inhibitor, protected the control OFs from ferroptosis. Both transcriptomic and proteomic analyses indicated glycolytic shift in the GO OFs. Metabolic profiling, PDK2 quantification, and oxygen consumption assay confirmed enhanced glycolysis in the GO OFs. Inhibition of glycolysis by PDK2 knockdown and dichloroacetic acid (DCA) promoted ferroptosis sensitivity in the GO OFs. The ferroptosis-sensitizing effects of DCA were also observed when the GO OFs were treated with GO-Igs. IGF1R overexpression in the GO OFs contributed to glycolysis shift. IGF1R inhibitory antibodies facilitated ferroptosis induction in the GO OFs, but the effects were less remarkable under GO-Igs treatment. CONCLUSION: These study findings establish that glycolysis facilitates ferroptosis resistance in the GO OFs, providing insights into the therapeutic role of glycolysis for GO treatment.

Modified procedure of anterior orbital exenteration enables eye socket reconstruction: A retrospective cohort study.

ABSTRACT: The conventional procedure of anterior orbital exenteration is unfavorable for eye socket reconstruction, whereas a modified procedure enables socket reconstruction and prosthesis fitting. Our study aims to compare the cosmetic outcomes between these 2 surgical techniques.We retrospectively recruited patients treated with modified or conventional exenteration during January 2015 to May 2021 in our hospital. The conventional approach was performed along with dermis-fat graft transplantation. The modified approach was conducted followed by eye socket reconstruction and eyelid blepharoplasty. The clinical data were collected and analyzed, including demographics, tumor characteristics, postoperative complications, tumor-related events, and cosmetic outcomes.Forty-nine patients were consecutively recruited in this study, including 22 cases of modified exenteration and 27 cases of conventional exenteration. Forty-four subjects (89.8%) were diagnosed with ocular surface malignancies (conjunctival melanoma and squamous cell carcinoma) and 5 subjects (10.2%) were diagnosed with extraocular stage of uveal melanoma. After follow-up for 31.8 ±â€Š17.1 months, the 1-, 2-, 5-year overall survival rate was calculated as 100%, 79.2%, and 59.2% in the Modified group, and 94.2%, 73.8%, and 51.5% in the Conventional group. Comparison of the survival curves showed no significant differences. In the Modified group, all patients received orbital implant placement and eye socket reconstruction. The implant motility was satisfactory in 12 cases (54.5%) with movements in 3 to 4 directions. The eyelid function was acceptable in 17 cases (77.3%) with no entropion, ectropion or lower lid laxity. Ocular prosthesis was delivered in 17 cases (77.3%) with successful fitting in 11 cases (64.7%). The self-rated cosmetic score was statistically (t test, P < .0001) higher in the Modified group (6.7 ±â€Š0.9) than the Conventional group (2.2 ±â€Š0.4).The modified approach to anterior orbital exenteration enables eye socket reconstruction and cosmetic rehabilitation while still preserves the curable chance for the treatment of advanced periocular/intraocular malignancies.

Quantitative T1 mapping MRI for the assessment of extraocular muscle fibrosis in thyroid-associated ophthalmopathy.

PURPOSE: We aimed to investigate the performance of T1 mapping and its histological correlation with extraocular muscle fibrosis in thyroid-associated ophthalmopathy (TAO). METHODS: We prospectively recruited 12 cases of active TAO, 12 cases of inactive TAO, and 15 cases of control subjects. All participants underwent magnetic resonance imaging (MRI) scan with pre-/postcontrast T1 mapping and short-time inversion-recovery (STIR) sequence. The images were analyzed to obtain precontrast T1, extracellular-volume (ECV) fraction on T1 mapping, and signal-intensity ratio (SIR) on STIR for each rectus. Muscle biopsy was performed at lateral rectus to quantify-collagen volume fraction, glycosaminoglycan (GAG)-volume fraction, and extracellular space component. The relationship between MRI and histopathology was examined with Pearson correlation coefficient. RESULTS: The active TAO group was characterized with GAG accumulation, while the inactive TAO group presented with substantial fibrosis. The MRI parameters achieved acceptable interobserver and intraobserver agreement. The precontrast T1 and ECV remarkably increased in the TAO groups than the control group, and ECV positively correlated with collagen-volume fraction (r = 0.913) and extracellular-space component (r = 0.886) in the inactive TAO group. The SIR statistically increased in the active TAO group, and SIR positively correlated with GAG-volume fraction in all three groups. The performance of ECV (cutoff > 48.1%) to screen out extraocular muscle fibrosis in inactive TAO was 60.9% sensitivity and 93.3% specificity. CONCLUSIONS: The ECV parameter on T1 mapping MRI is a reliable tool to quantify extraocular muscle fibrosis, providing insights into noninvasive evaluation of pathological changes in TAO orbit. TRIAL REGISTRATION NUMBER: ChiCTR2000040394; Date of registration: 28 November 2020.

The changes of retinal nerve fibre layer and ganglion cell layer with different severity of thyroid eye disease.

OBJECTIVES: To evaluate the changes of retinal nerve fibre layer (RNFL) and ganglion cell layer/inner plexiform layer (GCL/IPL) with the severity of thyroid eye disease (TED). METHODS: One hundred and forty-five eyes of 75 patients with TED and 70 eyes of 35 healthy controls were included. The eyes with TED were divided into mild group (35 eyes), moderate-to-severe group (42 eyes) and DON group (68 eyes). The thickness of RNFL and GCL/IPL were measured by optic coherence tomography (OCT). Clinical activity score (CAS), best corrected visual acuity (BCVA), intraocular pressure (IOP), proptosis and mean deviation (MD) by Humphrey perimetry were assessed. RESULTS: The CAS had significant difference between the three groups (p < 0.001). The proptosis and IOP were significantly higher in DON group and moderate-to-severe group than mild group (p < 0.05). The MD and BCVA were significantly worse in DON group compared with mild group and moderate-to-severe group (p < 0.001). The mean GCL/IPL thickness was thinnest in DON group (p < 0.001). The mean RNFL thickness had significant difference between moderate-to-severe group and DON group (p = 0.036). The mean GCL/IPL thickness had a significant correlation with MD (r = 0.449, p < 0.001) and VA (r = -0.388, p < 0.001), whereas the mean RNFL thickness had no significant correlation with MD (p = 0.082) or VA (p = 0.226). CONCLUSIONS: Subclinical optic neuropathy might progress in the patients with moderate-to-severe TED. OCT measurements of GCL/IPL and RNFL are useful to detect the early changes of optic nerve. The thinning of GCL/IPL might be a strong suggestion for closer vision follow-up and earlier decompression surgery.

Systematic review with meta-analysis: environmental and dietary differences of inflammatory bowel disease in Eastern and Western populations.

BACKGROUND: While the incidence of inflammatory bowel disease (IBD) has stabilised in the West, it is still increasing in several newly industrialised countries. AIMS: To investigate whether the environmental and dietary risk factors for IBD differ between Eastern and Western populations METHODS: We systematically searched PubMed, Embase, and Web of Science for studies published from inception through June 30, 2020. Data were pooled using a random effects model. RESULTS: Overall, 255 studies were assessed. We identified 25 risk factors for IBD, seven of which were noted in both Eastern and Western populations: family history of Crohn's disease [CD] or ulcerative colitis [UC], former smoking (CD/UC), smoking (CD), appendicectomy (CD), tonsillectomy (CD), meat and meat products (CD), and vitamin D deficiency (UC). The remaining factors, including urban living, current smoking, antibiotics, oral contraceptives, caesarean section, isotretinoin, total energy, fat, cholesterol, fatty acids and their sub-classifications, eggs, and soft drinks, were associated with an increased risk of IBD in Western or Eastern populations only. We identified 21 protective factors for IBD, among which eight were common in the East and West: farm animals (CD/UC), Helicobacter pylori infection (CD/UC), multiple births (CD), physical activity (CD), history of breastfeeding (CD), pets (UC), current smoking (UC), and coffee intake (UC). Ten factors conferred protection against IBD in Western populations only, whereas eight factors conferred protection against IBD in Eastern populations only. CONCLUSIONS: Numerous environmental and dietary factors influenced the development of IBD in both Western and Eastern populations, whereas certain factors influenced IBD risk differently in these populations.

Correlation between uniocular deviation and duction changes following different decompression surgeries in thyroid eye disease.

BACKGROUND: Postoperative ocular imbalance is an important problem for orbital decompression surgery in thyroid eye disease (TED). The aim of this study was to evaluate the changes in unilateral ocular deviation and duction following orbital decompression and discuss the biomechanics of ocular imbalance. METHODS: Fifty-four TED patients who underwent unilateral orbital decompression were included. Fifteen patients underwent 1-wall (deep lateral wall) decompression, 18 patients underwent 2-wall (deep lateral and medial wall) decompression and 21 patients underwent 3-wall (deep lateral, medial and inferior wall) decompression. Objective and subjective deviation of the operated eyes were evaluated using the prism test and synoptophore, respectively. Ocular ductions were measured using Hirschberg's method. The diameters of the extraocular rectus were measured by computed tomography. RESULTS: Ocular deviation and duction showed no significant difference after 1-wall decompression (p = 0.25-0.89). Esotropia increased after 2-wall decompression (p = 0.001-0.02), and hypotropia increased after 3-wall decompression (p = 0.02). Adduction increased but abduction decreased following 2-wall and 3-wall decompression (p < 0.05). Infraduction increased following 3-wall decompression (p < 0.001). Additionally, the increase in esotropia was significantly correlated with the increase in adduction and with the decrease in abduction (r = 0.37-0.63, p < 0.05). There were significant correlations between the diameter of the medial rectus and the increase in esotropia, the increase in adduction and the decrease in abduction postoperatively (r = 0.35-0.48, p < 0.05). CONCLUSIONS: The changes in ocular deviation and duction were different after 1-wall, 2-wall and 3-wall orbital decompression. The increased contractile force of the rectus may be an important reason for strabismus changes after orbital decompression surgery.

Orbital exenteration for conjunctival melanoma: comparison of long-term outcome between individualised and conventional techniques.

BACKGROUND: Growing evidence supports an individualised approach rather than radical surgery for conjunctival melanoma (CM). This study aimed to compare the long-term outcome between individualised and conventional exenteration techniques. METHODS: Our study retrospectively recruited advanced CM (clinical T3 stage) patients treated with individualised (13 cases) or conventional (18 cases) exenteration from June 2014 to April 2019. The individualised approach preserved at least three quadrants of the orbit, and the conventional procedures removed at least one third of the orbital tissues. The medical records were collected and analyzed during April 2020, including demographics, tumour characteristics, surgical details, postoperative rehabilitation and tumour-related prognosis. RESULTS: The tumour basal diameter was statistically (P = 0.011) larger in the conventional group (23.3 ± 7.6 mm) than in the individualised group (15.4 ± 6.3 mm). More tissues were preserved in the individualised group, resulting in a shorter duration of wound healing (2.1 ± 0.6 vs. 3.6 ± 2.0 weeks, P = 0.018) and less incidence of hollow appearance (15% vs. 72%, P = 0.003) than the conventional group. After follow-up for 39.3 ± 17.3 months, a comparison of survival curves showed no significant differences (P = 0.638) between the two groups. The 1- and 2-year overall survival rates were estimated as 100% and 80.0% in the individualised group, and 93.8% and 72.5% in the conventional group, respectively. Low or mixed pigmentation was identified as the risk factor for tumour-related mortality based on multivariate regression analysis. CONCLUSIONS: The individualised approach to exenteration offers improved aesthetic results while still maximises the curable chance for advanced CM.

LncRNA SNHG15 predicts poor prognosis in uveal melanoma and its potential pathways.

AIM: To evaluate the role of long noncoding RNA (lncRNA) SNHG15 and its potential pathways in uveal melanoma (UM). METHODS: The SNHG15 mRNA expression level and corresponding clinicopathological characteristics of 80 patients with UM were obtained from the Cancer Genome Atlas (TCGA) database and further analyzed. The SPSS 24.0 statistical software package was used for statistical analyses. To investigate the potential function of SNHG15 in UM, we conducted in-depth research on Gene Set Enrichment Analysis (GSEA). RESULTS: The univariate analysis revealed that the age, tumor diameter, pathological type, extrascleral extension, cancer status, and high expression of SNHG15 were statistical risk factors for death from all causes. The multivariate analysis suggested that the mRNA expression level of SNHG15 was an independent risk factor for death from all causes, as was age and pathological type. Kaplan-Meier survival analysis confirmed that UM patients with high SNHG15 expression might have a poor prognosis. In addition, SNHG15 was significantly differentially expressed in the different groups of tumor pathologic stage, metastasis and living status. Besides, the logistic regression analysis indicated that high SNHG15 expression group in UM was significantly associated with cancer status, pathologic stage, metastasis, and living status. Moreover, the GSEA indicated the potential pathways regulated by SNHG15 in UM. CONCLUSION: Our research suggests that SNHG15 may play a vital role as a potential marker in UM that predicts poor prognosis. Besides, GSEA indicates the underlying signaling pathways enriched differentially in SNHG15 high expression phenotype.

Histopathologic study of extraocular muscles in thyroid-associated ophthalmopathy coexisting with ocular myasthenia gravis: a case report.

BACKGROUND: Coexistence of thyroid-associated ophthalmopathy (TAO) and ocular myasthenia gravis (OMG) is very rare. Little is known about the orbital histopathology associated with this condition. The authors reported a case of TAO coexisting with OMG and explored the histopathologic changes in extraocular muscles. CASE PRESENTATION: A 32-year-old man complaint of bilateral proptosis for 2 years. The patient was documented with a history of OMG and was treated with blepharoplasty to correct ptosis 3 years prior to presentation. Physical examination revealed right upper eyelid retraction resulting from the eyelid surgery. Computed tomographic scan demonstrated bilateral enlargement of the extraocular muscles. Thyroid function test confirmed hyperthyroid status. The patient was diagnosed with TAO (clinical activity score = 2/7) coexisting with OMG. Orbital decompression surgery reduced proptosis but resulted in new onset of left upper eyelid retraction because of the increased motor impulses to sustain eyelid elevation. Extraocular muscles were sampled during surgery and subjected to histopathologic stain. The stain results were analyzed against samples from age-, gender- matched TAO and control (non-TAO non-OMG) subjects. The measurement of myofiber size and glycosaminoglycan/collagen-occupied area was repeated in 3 randomly chosen fields of each slide. The variation of myofiber size was larger in the TAO + OMG (289.9 ± 142.5 µm2) samples than the TAO (544.1 ± 160.6 µm2) and control (157.0 ± 47.7 µm2) samples. Glycosaminoglycan was more abundant in the TAO + OMG (48.8 ± 12.2%) samples than the TAO (28.4 ± 3.6%) and control (3.3 ± 0.8%) samples. Collagen fibers accumulated in the TAO (60.5 ± 6.4%) samples but not in the TAO + OMG (36.1 ± 4.3%) and control (33.9 ± 2.7%) samples. Typical OMG changes were observed in the TAO + OMG samples but not in the TAO and control samples. These changes included central nuclei, aggregation of mitochondria and fiber type grouping. The histopathologic findings of TAO + OMG were summarized as inhomogeneously enlarged muscle fibers and predominantly endomysial accumulation of glycosaminoglycan. CONCLUSION: This study highlights the possibility of TAO coexisting with OMG and demonstrates the histopathologic features in this rare condition.

lncRNA SNHG7 affects malignant tumor behaviors through downregulation of EZH2 in uveal melanoma cell lines.

Previous studies have demonstrated that the long non-coding RNA, small nucleolar RNA host gene 7 (SNHG7) plays an important role in several types of cancer; however, its role in the development of uveal melanoma (UM) remains unclear. The present study investigated the effect of SNHG7 on the prognosis of UM, as well as on cell proliferation, cell cycle and apoptosis of UM cell lines. Furthermore, the present study aimed to determine the molecular mechanisms underlying these effects. The association between SNHG7 and prognosis of UM was analyzed using detailed SNHG7 mRNA expression data and clinical information from The Cancer Genome Atlas database. Reverse transcription-quantitative PCR was used in order to detect the differential expression of SNHG7 in UM tissues and cell lines. Cell proliferation was detected using Cell Counting Kit-8 assays, following overexpression of SNHG7. A cell cycle assay was performed using propidium iodide/RNase staining. An apoptosis assay was performed using the Annexin-V-Fluorescein isothiocyanate apoptosis detection kit. The expression of enhancer of zeste homolog 2 (EZH2) was measured via western blotting. The results of the present study indicated that low expression of SNHG7 was associated with poor prognosis. Furthermore, increasing the expression of SNHG7 inhibited the proliferation of UM cells, suppressed cell cycle progression and promoted apoptosis. Western blot analysis results revealed that overexpression of SNHG7 downregulated EZH2 protein expression levels in UM cell lines. The results of the present study demonstrated that SNHG7 inhibited malignant transformation of UM cells by regulating EZH2 expression.