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1.
Front Med (Lausanne) ; 11: 1381758, 2024.
Article En | MEDLINE | ID: mdl-38562374

Segmentation of corneal layer interfaces in optical coherence tomography (OCT) images is important for diagnostic and surgical purposes, while manual segmentation is a time-consuming and tedious process. This paper presents a novel technique for the automatic segmentation of corneal layer interfaces using customized initial layer estimation and a gradient-based segmentation method. The proposed method was also extended to three-dimensional OCT images. Validation was performed on two corneal datasets, one with 37 B-scan images of healthy human eyes and the other with a 3D volume scan of a porcine eye. The approach showed robustness in extracting different layer boundaries in the low-SNR region with lower computational cost but higher accuracy compared to existing techniques. It achieved segmentation errors below 2.1 pixels for both the anterior and posterior layer boundaries in terms of mean unsigned surface positioning error for the first dataset and 2.6 pixels (5.2 µm) for segmenting all three layers that can be resolved in the second dataset. On average, it takes 0.7 and 0.4 seconds to process a cross-sectional B-scan image for datasets one and two, respectively. Our comparative study also showed that it outperforms state-of-the-art methods for quantifying layer interfaces in terms of accuracy and time efficiency.

2.
J Bioenerg Biomembr ; 56(3): 297-309, 2024 Jun.
Article En | MEDLINE | ID: mdl-38602631

Ferroptosis of the retinal pigment epithelial (RPE) cells leads to retinal neuron injury and even visual loss. Our study aims to investigate the role of the SET domain with lysine methyltransferase 7/9 (SET7/9) in regulating high glucose (HG)-induced ferroptosis in RPE cells. The cell model was established by HG treatment. The levels of SET7/9 and Sirtuin 6 (SIRT6) were inhibited and Runt-related transcription factor 1 (RUNX1) was overexpressed through cell transfection, and then their levels in ARPE-19 cells were detected. Cell viability and apoptosis was detected. The levels of reactive oxygen species, malondialdehyde, glutathione, ferrous ion, glutathione peroxidase 4, and acyl-CoA synthetase long-chain family member 4 were detected. SET7/9 and trimethylation of histone H3 at lysine 4 (H3K4me3) levels in the RUNX1 promoter region and RUNX1 level in the SIRT6 promoter region were measured. The relationship between RUNX1 and SIRT6 was verified. SET7/9 and RUNX1 were highly expressed while SIRT6 was poorly expressed in HG-induced ARPE-19 cells. SET7/9 inhibition increased cell viability and inhibited cell apoptosis and ferroptosis. Mechanistically, SET7/9 increased H3K4me3 on the RUNX1 promoter to promote RUNX1, and RUNX1 repressed SIRT6 expression. Overexpression of RUNX1 or silencing SIRT6 partially reversed the inhibitory effect of SET7/9 silencing on HG-induced ferroptosis. In conclusion, SET7/9 promoted ferroptosis of RPE cells through the SIRT6/RUNX1 pathway.


Ferroptosis , Glucose , Histone-Lysine N-Methyltransferase , Retinal Pigment Epithelium , Humans , Retinal Pigment Epithelium/metabolism , Retinal Pigment Epithelium/pathology , Glucose/metabolism , Histone-Lysine N-Methyltransferase/metabolism , Histone-Lysine N-Methyltransferase/genetics , Epigenesis, Genetic , Histones/metabolism , Methylation , Cell Line , Epithelial Cells/metabolism , Sirtuins/metabolism , Sirtuins/genetics
3.
Curr Med Chem ; 2024 Jan 03.
Article En | MEDLINE | ID: mdl-38173196

BACKGROUND: Metastasis is a major cause of death in UM, highlighting the need to use highly specific and sensitive prognostic markers to identify patients with a risk of developing metastasis. AIMS: The aim of this study was to improve the current precision treatment for patients with metastatic uveal melanoma (UM). OBJECTIVE: The objective of this work was to investigate the heterogeneity between primary human UM and metastatic UM at the single-cell level and to discover potential molecules regulating UM metastasis. METHODS: Seurat R toolkit was employed to analyze single-cell sequencing data of UM and to identify differentially expressed genes (DEGs) between primary and metastatic UM. Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were performed on the DEGs from the bulk RNA-seq cohort to develop a prognostic model. Based on the model, patients were divided into high and low groups. The correlations among the risk score, immune indicators, immune checkpoint blockade (ICB) therapy, and anti-tumor drug therapy were analyzed. RESULTS: Cell types in primary UM and metastatic UM tumors include B/plasma cells, endothelial cells, melanocytes, monocytes/macrophages, photoreceptor cells, and T cells. Among 157 DEGs between the two tumor types, S100A4, PDE4B, CHCHD10, NSG1, and C4orf48 were selected to construct a prognostic model. The model could accurately and independently predict response to ICB treatment and sensitivity to antineoplastic drugs for UM patients as well as their immune infiltration levels, risk of death, and metastasis possibility. CONCLUSIONS: This study analyzed the tumor ecosystem of primary and metastatic UM, providing a metastasis-related model that could be used to evaluate the prognosis, risk of metastasis, immunotherapy, and efficacy of antineoplastic drug treatment of UM.

4.
Br J Ophthalmol ; 108(3): 432-439, 2024 02 21.
Article En | MEDLINE | ID: mdl-36596660

BACKGROUND: Optical coherence tomography angiography (OCTA) enables fast and non-invasive high-resolution imaging of retinal microvasculature and is suggested as a potential tool in the early detection of retinal microvascular changes in Alzheimer's Disease (AD). We developed a standardised OCTA analysis framework and compared their extracted parameters among controls and AD/mild cognitive impairment (MCI) in a cross-section study. METHODS: We defined and extracted geometrical parameters of retinal microvasculature at different retinal layers and in the foveal avascular zone (FAZ) from segmented OCTA images obtained using well-validated state-of-the-art deep learning models. We studied these parameters in 158 subjects (62 healthy control, 55 AD and 41 MCI) using logistic regression to determine their potential in predicting the status of our subjects. RESULTS: In the AD group, there was a significant decrease in vessel area and length densities in the inner vascular complexes (IVC) compared with controls. The number of vascular bifurcations in AD is also significantly lower than that of healthy people. The MCI group demonstrated a decrease in vascular area, length densities, vascular fractal dimension and the number of bifurcations in both the superficial vascular complexes (SVC) and the IVC compared with controls. A larger vascular tortuosity in the IVC, and a larger roundness of FAZ in the SVC, can also be observed in MCI compared with controls. CONCLUSION: Our study demonstrates the applicability of OCTA for the diagnosis of AD and MCI, and provides a standard tool for future clinical service and research. Biomarkers from retinal OCTA images can provide useful information for clinical decision-making and diagnosis of AD and MCI.


Alzheimer Disease , Cognitive Dysfunction , Humans , Fluorescein Angiography/methods , Retinal Vessels/diagnostic imaging , Tomography, Optical Coherence/methods , Alzheimer Disease/diagnostic imaging , Microvessels/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging
5.
Front Med (Lausanne) ; 10: 1280714, 2023.
Article En | MEDLINE | ID: mdl-37869163

Purpose: Fast and automated reconstruction of retinal hyperreflective foci (HRF) is of great importance for many eye-related disease understanding. In this paper, we introduced a new automated framework, driven by recent advances in deep learning to automatically extract 12 three-dimensional parameters from the segmented hyperreflective foci in optical coherence tomography (OCT). Methods: Unlike traditional convolutional neural networks, which struggle with long-range feature correlations, we introduce a spatial and channel attention module within the bottleneck layer, integrated into the nnU-Net architecture. Spatial Attention Block aggregates features across spatial locations to capture related features, while Channel Attention Block heightens channel feature contrasts. The proposed model was trained and tested on 162 retinal OCT volumes of patients with diabetic macular edema (DME), yielding robust segmentation outcomes. We further investigate HRF's potential as a biomarker of DME. Results: Results unveil notable discrepancies in the amount and volume of HRF subtypes. In the whole retinal layer (WR), the mean distance from HRF to the retinal pigmented epithelium was significantly reduced after treatment. In WR, the improvement in central macular thickness resulting from intravitreal injection treatment was positively correlated with the mean distance from HRF subtypes to the fovea. Conclusion: Our study demonstrates the applicability of OCT for automated quantification of retinal HRF in DME patients, offering an objective, quantitative approach for clinical and research applications.

6.
Front Aging Neurosci ; 15: 1159711, 2023.
Article En | MEDLINE | ID: mdl-37671084

Aims: Observational studies have shown that sleep pattern is associated with age-related macular degeneration (AMD), but whether sleep pattern is a causal factor for AMD remains unclear. This study aims to use Mendelian randomization (MR) analysis to investigate the potential causal relationship between sleep traits and AMD. Methods: This is a two-sample MR study. The single-nucleotide polymorphisms associated with AMD and early AMD were selected as the outcome from two different genome-wide association studies (GWAS): the early AMD GWAS with 14,034 cases and 91,214 controls, and AMD GWAS with 3,553 cases and 147,089 controls. The datasets of sleep duration, daytime dozing, and sleeplessness were used as exposure, which comprised nearly 0.46 million participants. Inverse-variance weighted method was used as the main result, and comprehensive sensitivity analyses were conducted to estimate the robustness of identified associations and the impact of potential horizontal pleiotropy. Results: Through MR analysis, we found that sleep duration was significantly associated with AMD (OR = 0.983, 95% CI = 0.970-0.996, P-value = 0.01). We also found suggestive evidence for the association of genetically predicted sleep duration with early AMD, which showed a consistent direction of effect with a marginal significance (OR = 0.724, 95% CI = 0.503-1.041, P-value = 0.08). Sensitivity analyses further supported the robustness of the causal relationship between sleep duration and AMD. However, we were unable to determine the relationship between daytime dozing or sleeplessness and AMD (including early AMD) (P-value > 0.05). Conclusion: Sleep duration affects the causal risk for AMD; that is, longer sleep duration reduces the risk of AMD, while shorter sleep duration increases the risk of AMD. Although the influence is minimal, keeping adequate sleep duration is recommended, especially for patients with intermediate or advanced AMD.

7.
Genes Nutr ; 18(1): 11, 2023 Jul 21.
Article En | MEDLINE | ID: mdl-37479984

BACKGROUND: Age-related macular degeneration (AMD) is one of the major causes of vision loss. Early AMD needs to be taken seriously, but the causal effects of lipid biomarkers on early AMD remain unclear. METHODS: In this study, two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between seven serum lipid biomarkers (apolipoprotein A (ApoA), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], and triglycerides (TG)) and risk of early AMD. In total, 14,034 cases and 91,214 controls of European ancestry were included in the analysis (number of SNPs = 11,304,110). RESULTS: MR estimates revealed that a higher HDL-C level is strongly associated with increased risk of early AMD (OR = 1.25, 95% CI: 1.15-1.35, P = 2.61 × 10-8). In addition, level of ApoA is also positively associated with risk of early AMD (OR = 2.04, 95% CI: 1.50-2.77, P = 6.27 × 10-6). Conversely, higher levels of TG significantly decrease the risk of early AMD (OR = 0.77, 95% CI: 0.71-0.84, P = 5.02 × 10-10). Sensitivity analyses further supported these associations. Moreover, multivariable MR analyses, adjusted for the effects of correlated lipid biomarkers, yielded similar results. CONCLUSION: This study identifies causal relationships between elevated circulating HDL-C/ApoA levels and increased risk of early AMD, in addition to finding that TG specifically reduces the risk of early AMD. These findings contribute to a better understanding of the role of lipid metabolism in drusen formation, particularly in early AMD development.

8.
Int J Ophthalmol ; 16(5): 730-735, 2023.
Article En | MEDLINE | ID: mdl-37206171

AIM: To introduce and evaluate the clinical efficacy of a new technique, the use of viscoelastic substances (VS) to close leaking sclerotomy in 23G microincision vitrectomy, and to observe its effect on the visual acuity and intraocular pressure (IOP) of patients. METHODS: Patients who underwent 23G vitrectomy in Ningbo Eye Hospital before the use of VS technique (June 2019 to September 2020) and after the use of VS technique (October 2020 to December 2021) were selected as the subjects of this study. The above cases underwent operation by the same surgeon and were retrospectively analyzed. VS technique was used as the alternative to suturing, in which a small amount of VS was injected at the leaking sclerotomy and then gently massaged to confirm leaking sclerotomy closure. RESULTS: A total of 174 eyes were covered in the study, including 84 eyes in the control group (before the use of VS technique) and 90 eyes in the VS technique group. The number of eyes that needed to be sutured decreased considerably from 42.9% in the control group to 3.3% in the VS technique group, and the proportion of subconjunctival hemorrhage at 1-2d after surgery decreased remarkably from 35.7% in the control group to 2.2% in the VS technique group. No substantial differences in the incidence of mean IOP and low IOP were found between 1-2 and 3-20d after surgery in the VS technique group. No major complications associated with VS technique were identified during the study. CONCLUSION: In 23G microincision vitrectomy, VS technique is a safe, simple, and effective method to close leaking sclerotomy.

9.
Front Cell Dev Biol ; 11: 1181305, 2023.
Article En | MEDLINE | ID: mdl-37215081

Background: Ultra-Wide-Field (UWF) fundus imaging is an essential diagnostic tool for identifying ophthalmologic diseases, as it captures detailed retinal structures within a wider field of view (FOV). However, the presence of eyelashes along the edge of the eyelids can cast shadows and obscure the view of fundus imaging, which hinders reliable interpretation and subsequent screening of fundus diseases. Despite its limitations, there are currently no effective methods or datasets available for removing eyelash artifacts from UWF fundus images. This research aims to develop an effective approach for eyelash artifact removal and thus improve the visual quality of UWF fundus images for accurate analysis and diagnosis. Methods: To address this issue, we first constructed two UWF fundus datasets: the paired synthetic eyelashes (PSE) dataset and the unpaired real eyelashes (uPRE) dataset. Then we proposed a deep learning architecture called Joint Conditional Generative Adversarial Networks (JcGAN) to remove eyelash artifacts from UWF fundus images. JcGAN employs a shared generator with two discriminators for joint learning of both real and synthetic eyelash artifacts. Furthermore, we designed a background refinement module that refines background information and is trained with the generator in an end-to-end manner. Results: Experimental results on both PSE and uPRE datasets demonstrate the superiority of the proposed JcGAN over several state-of-the-art deep learning approaches. Compared with the best existing method, JcGAN improves PSNR and SSIM by 4.82% and 0.23%, respectively. In addition, we also verified that eyelash artifact removal via JcGAN could significantly improve vessel segmentation performance in UWF fundus images. Assessment via vessel segmentation illustrates that the sensitivity, Dice coefficient and area under curve (AUC) of ResU-Net have respectively increased by 3.64%, 1.54%, and 1.43% after eyelash artifact removal using JcGAN. Conclusion: The proposed JcGAN effectively removes eyelash artifacts in UWF images, resulting in improved visibility of retinal vessels. Our method can facilitate better processing and analysis of retinal vessels and has the potential to improve diagnostic outcomes.

10.
Int J Ophthalmol ; 16(4): 505-513, 2023.
Article En | MEDLINE | ID: mdl-37077497

AIM: To investigate whether nintedanib can inhibit pterygium cells through the fibroblast growth factor receptor 2 (FGFR2)/extracellular-signal-regulated kinase (ERK) pathway. METHODS: Human primary pterygium cells were cultured in vitro. After treatment with nintedanib, the cell morphology was observed under microscopy, the morphological changes of the nucleus were observed after DAPI staining, apoptosis was analyzed by Annexin-V FITC/PI double staining, and the changes of apoptosis-associated proteins were detected by Western blot. The binding ability of nintedanib to FGFR2 was predicted by molecular docking. Finally, by silencing FGFR2, we explored whether nintedanib inhibited FGFR2/ERK pathway. RESULTS: The results showed that nintedanib inhibited the growth of pterygium cells and caused nuclear pyknosis. The results of Annexin-VFITC/PI double staining showed that nintedanib was able to induce early and late apoptosis of pterygium cells, significantly increasing the expression of apoptosis-associated proteins Bax and cleaved-Caspase3 (P<0.05), and reducing the expression of Bcl-2 (P<0.05). In addition, nintedanib significantly inhibited ERK1/2 phosphorylation through FGFR2 (P<0.05). After silencing the expression of FGFR2, there was no significant difference in the inhibition of ERK1/2 phosphorylation by nintedanib (P>0.05). CONCLUSION: Nintedanib induces apoptosis of pterygium cells by inhibiting FGFR2/ERK pathway.

11.
Invest Ophthalmol Vis Sci ; 64(3): 7, 2023 03 01.
Article En | MEDLINE | ID: mdl-36867130

Purpose: Little is known about whether sugar intake is a risk factor for myopia, and the influence of glycemic control remains unclear, with inconsistent results reported. This study aimed to clarify this uncertainty by evaluating the link between multiple glycemic traits and myopia. Methods: We employed a two-sample Mendelian randomization (MR) design using summary statistics from independent genome-wide association studies. A total of six glycemic traits, including adiponectin, body mass index, fasting blood glucose, fasting insulin, hemoglobin A1c (HbA1c), and proinsulin levels, were used as exposures, and myopia was used as the outcome. The inverse-variance-weighted (IVW) method was the main applied analytic tool and was complemented with comprehensive sensitivity analyses. Results: Out of the six glycemic traits studied, we found that adiponectin was significantly associated with myopia. The genetically predicted level of adiponectin was consistently negatively associated with myopia incidence: IVW (odds ratio [OR] = 0.990; P = 2.66 × 10-3), MR Egger (OR = 0.983; P = 3.47 × 10-3), weighted median method (OR = 0.989; P = 0.01), and weighted mode method (OR = 0.987; P = 0.01). Evidence from all sensitivity analyses further supported these associations. In addition, a higher HbA1c level was associated with a greater risk of myopia: IVW (OR = 1.022; P = 3.06 × 10-5). Conclusions: Genetic evidence shows that low adiponectin levels and high HbA1c are associated with an increased risk of myopia. Given that physical activity and sugar intake are controllable variables in blood glycemia treatment, these findings provide new insights into potential strategies to delay myopia onset.


Adiponectin , Myopia , Humans , Genome-Wide Association Study , Glycated Hemoglobin , Sugars
12.
Article En | MEDLINE | ID: mdl-36982133

Improving citizen epidemic prevention information literacy is one of the most cost-efficient and important measures to improve people's epidemic prevention abilities to effectively deal with future public health crises. Epidemic prevention information literacy is beneficial to improve individuals' ability to deal with public health crises in the future. By summarizing related domestic and international research, and utilizing an empirical methodology, we constructed an epidemic prevention information literacy assessment model with good reliability, validity, and model fit. The model is composed of four indicators: (1) "epidemic prevention information awareness"; (2) "epidemic prevention information knowledge"; (3) "epidemic prevention information ability"; (4) "epidemic prevention information morality". We used the model to assess the epidemic prevention information literacy of Chinese citizens. The results showed the following: (1) the overall level of the epidemic prevention information literacy of Chinese citizens was comparatively high, however, its development was unbalanced, and the capability and moral levels of the epidemic prevention information were comparatively low; (2) the four dimensions of the epidemic prevention information literacy were different in terms of the citizens' education levels and locations. We analyzed the probable causes of these problems, and we propose specific corresponding countermeasures. The research provides a set of methods and norms for the evaluation of citizen epidemic prevention information literacy in the post-epidemic era.


Health Literacy , Humans , Reproducibility of Results , Health Literacy/methods , Information Literacy , Educational Status , China/epidemiology
13.
Funct Integr Genomics ; 23(1): 49, 2023 Jan 27.
Article En | MEDLINE | ID: mdl-36705739

Uveal melanoma (UM), a frequently seen adulthood primary ocular malignancy, shows high aggressiveness. Accumulating studies have revealed the crucial effects of microRNAs (miRNAs) on tumorigenesis and development in various human tumors. miR-204, the cancer-associated miRNA, shows dysregulation and is related to several human malignancies, but its effect on UM remains unknown. The present work focused on exploring miR-204's effect on UM and elucidating its possible molecular mechanisms. According to our results, miR-204 expression markedly increased within both UM tissues and cell lines. As revealed by functional analysis, miR-204 suppressed UM cell invasion and migration. Besides, RAB22A expression decreased through directly binding miR-204 into the corresponding 3' untranslated region (3'UTR) in UM cells. Furthermore, the RAB22A mRNA level increased, which was negatively related to the miR-204 level within UM samples. As revealed by mechanical research, miR-204 exerted its inhibition on the invasion and migration of UM cells via RAB22A. Taken together, this study suggested the tumor-suppressing effect of miR-204 on UM through down-regulating RAB22A. Thus, miR-204 may serve as the new anti-UM therapeutic target.


Melanoma , MicroRNAs , Humans , Adult , Cell Line, Tumor , MicroRNAs/genetics , MicroRNAs/metabolism , Melanoma/genetics , Melanoma/metabolism , Melanoma/pathology , Cell Movement/genetics , Cell Proliferation , Gene Expression Regulation, Neoplastic , rab GTP-Binding Proteins/genetics , rab GTP-Binding Proteins/metabolism
14.
BMC Ophthalmol ; 22(1): 517, 2022 Dec 30.
Article En | MEDLINE | ID: mdl-36585631

BACKGROUND: Infectious keratitis, a medical emergency with acute and rapid disease progression may lead to severe visual impairment and even blindness. Herein, an antimicrobial polypeptide from Crassostrea hongkongensis, named URP20, was evaluated for its therapeutic efficacy against keratitis caused by Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) infection in rats, respectively. METHODS: A needle was used to scratch the surface of the eyeballs of rats and infect them with S. aureus and E.coli to construct a keratitis model. The two models were treated by giving 100 µL 100 µM URP20 drops. Positive drugs for S. aureus and E. coli infection were cefazolin eye drops and tobramycin eye drops, respectively. For the curative effect, the formation of blood vessels in the fundus was observed by a slit lamp (the third day). At the end of the experiment, the condition of the injured eye was photographed by cobalt blue light using 5 µL of 1% sodium fluorescein. The pathological damage to corneal tissues was assessed using hematoxylin-eosin staining, and the expression level of vascular endothelial growth factor (VEGF) was detected by immunohistochemistry. RESULTS: URP20 alleviated the symptoms of corneal neovascularization as observed by slit lamp and cobalt blue lamp. The activity of S. aureus and E.coli is inhibited by URP20 to protect corneal epithelial cells and reduce corneal stromal bacterial invasion. It also prevented corneal thickening and inhibited neovascularization by reducing VEGF expression at the cornea. CONCLUSION: URP20 can effectively inhibit keratitis caused by E.coli as well as S. aureus in rats, as reflected by the inhibition of corneal neovascularization and the reduction in bacterial damage to the cornea.


Corneal Neovascularization , Escherichia coli Infections , Keratitis , Staphylococcal Infections , Rats , Animals , Staphylococcus aureus , Corneal Neovascularization/pathology , Vascular Endothelial Growth Factor A , Escherichia coli , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Keratitis/drug therapy , Keratitis/prevention & control , Keratitis/microbiology , Cornea/pathology , Escherichia coli Infections/drug therapy , Escherichia coli Infections/pathology , Ophthalmic Solutions/pharmacology
15.
Comput Struct Biotechnol J ; 20: 3182-3194, 2022.
Article En | MEDLINE | ID: mdl-35782742

Uveal melanoma (UM) represents the most common primary intraocular malignancy in adults and is characterized by aggressive behaviors and a lack of targeted therapies. Hypoxia-targeted therapy has become a promising new therapeutic strategy in tumors. Therefore, a better understanding of the tumor hypoxia microenvironment is critical to improve the treatment efficacy of UM. In this study, we conducted an extensive multi-omics analysis to explore the heterogeneity and prognostic significance of the hypoxia microenvironment. We found that UM revealed the most significant degree of intertumoral heterogeneity in hypoxia by quantifying tumor hypoxia compared with other solid tumor types. Then we systematically correlated the hypoxia phenotypes with clinicopathological features and found that hypoxic UM tumors were associated with an increased risk of metastasis, more aggressive phenotypes, and unfavorable clinical outcomes. Integrative multi-omics analyses identified multidimensional molecular alterations related to hypoxia phenotypes, including elevated genome instability, co-occurring of 8q arm gains and loss of chromosome 3, and BAP1 mutations. Furthermore, hypoxic UM tumors could be characterized by increased CD8+ T cell infiltration and decreased naïve B cell and dysregulated metabolic pathways. Finally, we introduced DNN2HM, an interpretable deep neural network model to decode hypoxia phenotypes from multi-omics data. We showed that the DNN2HM improves hypoxia phenotype prediction and robustly predicts tumor aggressiveness and prognosis in different multi-center datasets. In conclusion, our study provides novel insight into UM tumor microenvironment, which may have clinical implications for future rationalized hypoxia-targeted therapy.

16.
J Cataract Refract Surg ; 48(7): 859-862, 2022 07 01.
Article En | MEDLINE | ID: mdl-35546428

A technique using the single-string, closed-loop fixation method to reposit dislocated triple-looped haptic intraocular lens (IOL)-capsular bag complex is described. The long needle or curved needle with a 10-0/8-0 polypropylene suture and a 27/30-gauge needle were used as the guide needle to pass through the fenestrated haptics twice. The scleral interlaminar course was used as the fixed point. Last, a fixation knot was created in the sclerotomy by the 2 ends of the thread to close the suture loop for IOL fixation. Another knot was created about 2 to 3 mm from the exit point and was intrasclerally anchored by the aid of the attached needle. 4 eyes from 4 consecutive patients were studied retrospectively; during all follow-up visits, the IOLs were well centered and stable, and no suture erosion, hypotony, scleral atrophy, chronic inflammation, retinal tears, and/or detachments were observed.


Haptic Technology , Lenses, Intraocular , Humans , Retrospective Studies , Sclera/surgery , Suture Techniques , Sutures , Visual Acuity
17.
NPJ Syst Biol Appl ; 8(1): 18, 2022 05 24.
Article En | MEDLINE | ID: mdl-35610253

Uveal melanoma (UM) is the most common primary malignant intraocular tumor. The use of precision medicine for UM to enable personalized diagnosis, prognosis, and treatment require the development of computer-aided strategies and predictive tools that can identify novel high-confidence susceptibility genes (HSGs) and potential therapeutic drugs. In the present study, a computational framework via propagation modeling on integrated multi-layered molecular networks (abbreviated as iUMRG) was proposed for the systematic inference of HSGs in UM. Under the leave-one-out cross-validation experiments, the iUMRG achieved superior predictive performance and yielded a higher area under the receiver operating characteristic curve value (0.8825) for experimentally verified SGs. In addition, using the experimentally verified SGs as seeds, genome-wide screening was performed to detect candidate HSGs using the iUMRG. Multi-perspective validation analysis indicated that most of the top 50 candidate HSGs were indeed markedly associated with UM carcinogenesis, progression, and outcome. Finally, drug repositioning experiments performed on the HSGs revealed 17 potential targets and 10 potential drugs, of which six have been approved for UM treatment. In conclusion, the proposed iUMRG is an effective supplementary tool in UM precision medicine, which may assist the development of new medical therapies and discover new SGs.


Melanoma , Uveal Neoplasms , Humans , Melanoma/drug therapy , Melanoma/genetics , Precision Medicine , Uveal Neoplasms/drug therapy , Uveal Neoplasms/genetics , Uveal Neoplasms/pathology
18.
J Healthc Eng ; 2022: 2185547, 2022.
Article En | MEDLINE | ID: mdl-35083023

According to the latest data from the Bureau of Disease Control and Prevention of the National Health and Family Planning Commission, China currently has 199.6 million diabetic patients and has become the world's largest country with diabetes. The prevalence rate is as high as 14.3%, which is much higher than the world average of 5.8%. The primary-level ophthalmic screening service is one of the important tasks to improve primary-level medical services, and the corresponding ophthalmic imaging diagnosis technology is an important support for primary-level medical and health services. Therefore, it is very necessary for us to study the application of artificial intelligence image recognition technology for diabetic retinopathy under the medical consortium mode and to study the precise initial diagnosis, precise referral, and precise follow-up of diabetic retina under the medical conjoined mode, so as to better promote the transformation of the ophthalmology primary service model. Based on this background, in this article, we have proposed and carried out the following solution: (1) diabetes data collation. Based on medical artificial intelligence technology, this paper collected 2,265 electronic medical records from an eye hospital in Ningbo and selected 2,000 qualified medical records for data integration and preprocessing. The contents of electronic medical records mainly include age, gender, and examination records. (2) Establish diabetic retinopathy diagnosis model based on neural network algorithm. This article first uses the classic algorithm of BP neural network for modeling, chooses the Levenberg-Marquardt method as the training function, and selects 10 hidden layer units through comparison experiments. After that, ophthalmologists assessed 80 sets of test results and determined the right diagnosis rate. Finally, this article compares and analyzes the accuracy of the two routes in 80 tests.


Diabetes Mellitus , Diabetic Retinopathy , Artificial Intelligence , Diabetic Retinopathy/diagnostic imaging , Humans , Mass Screening , Neural Networks, Computer , Retina
19.
Sci Rep ; 11(1): 23885, 2021 12 13.
Article En | MEDLINE | ID: mdl-34903819

Intravitreal anti-VEGF (anti-vascular endothelial growth factor) biologics have revolutionized the pharmacological management of chorioretinal diseases. However, the systemic adverse events such as stroke or bleeding are the concerns for many patients and physicians. The mechanism to develop these side effects are poorly understood. Consecutive 95 patients with retinal diseases were studied for their blood activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR), and concentration of fibrinogen before and after intravitreal conbercept. Additionally, plasma nitric oxide (NO) and endothelin-1 (ET-1) were investigated on 38 of the 95 patients. Compared with the pre-injection, 4-week post-injection values of APTT and PT were increased by 0.582 s (p = 0.038, paired t test) and by 0.086 s (p = 0.080, paired t test; p = 0.0475, Sign test), respectively. At the same time, fibrinogen decreased by 0.048 g/L. Plasma levels of NO or ET-1 or VEGF did not significantly change from pre-injection levels. Our findings advanced the understanding of mechanism for systemic side effects associated with intravitreal anti-VEGF and emphasized paying more attention to higher risk of possible bleedings for patients following intravitreal conbercept.


Blood Coagulation/drug effects , Endothelin-1/blood , Nitric Oxide/blood , Recombinant Fusion Proteins/adverse effects , Retinal Diseases/drug therapy , Aged , Female , Fibrinogen/metabolism , Humans , Intravitreal Injections , Male , Middle Aged , Prothrombin/metabolism , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/therapeutic use , Thromboplastin/metabolism
20.
J Ocul Pharmacol Ther ; 37(10): 591-596, 2021 12.
Article En | MEDLINE | ID: mdl-34678098

Purpose: To compare the clinical effects of postoperative versus perioperative injection of anti-vascular endothelial growth factor (VEGF) drugs before and after pars plana vitrectomy (PPV) in patients with vitreous hemorrhage secondary to polypoidal choroidal vasculopathy (PCV). Methods: This was a retrospective study of patients who underwent PPV due to vitreous hemorrhage between October 2013 and June 2019 at Ningbo Eye Hospital. The patients who underwent PPV surgery due to PCV-secondary vitreous hemorrhage were included. The primary outcome was the changes in best-corrected visual acuity. The secondary outcome was the central macular thickness. Results: Compared with the postoperative group (n = 20), the perioperative group (n = 18) showed a smaller number of postoperative anti-VEGF injections (5.1 ± 0.8 vs. 8.0 ± 1.5, P < 0.05) and lower frequencies of early hyphema (5.6% vs. 30.0%, P < 0.05), and recurrent vitreous hemorrhage (11.1% vs. 30.0%, P < 0.05). The logarithm of minimal angle resolution (LogMAR) was smaller in the perioperative group compared with the postoperative group at 1 week, 1 month, and 3 months after PPV (P < 0.05), but there were no differences thereafter. Compared with the postoperative group, the perioperative group had thinner fovea at 1 week, 1 month, and 3 months (P < 0.05), but the differences disappeared after 3 months. Conclusion: In patients with PCV and vitreous hemorrhage, compared with postoperative anti-VEGF, perioperative anti-VEGF could reduce the difficulty of surgery and reduce the occurrence of postoperative complications, but there were no differences in long-term vision and macular thickness after surgery.


Choroidal Neovascularization/surgery , Postoperative Complications/epidemiology , Vascular Endothelial Growth Factors/antagonists & inhibitors , Vitrectomy/methods , Vitreous Hemorrhage/surgery , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Visual Acuity , Vitrectomy/adverse effects
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