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AIM: To report a one-year clinical outcomes of low-dose laser cycloplasty (LCP) among malignant glaucoma patients. METHODS: In this prospective, multicenter, non-comparative clinical study, participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China. Patients were followed up at 1wk, 1, 3, 6, and 12mo. Intraocular pressure (IOP), number of glaucoma medications, anterior chamber depth (ACD), and complications were recorded. Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy. Recurrence was defined by the presence of a shallow or ï¬at anterior chamber after initial recovery from treatment. RESULTS: A total of 34 eyes received LCP. Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg (P<0.001) with 2.9±1.6 medications (P=0.046) at 1d, and 17.4±6.7 mm Hg (P<0.001) with 1.3±1.7 medications (P<0.001) at 12mo. The ACD increased from 1.1±0.8 mm at baseline to 1.7±1.0 mm and to 2.0±0.5 mm at 1d and 12mo, respectively. A total of 32 (94.1%) eyes achieved initial anatomical success. During follow-up, 2 (5.9%) eyes failed and 8 (23.5%) eyes relapsed, yielding a 12-month anatomical success rate of 64.3%. Complications including anterior synechia (8.82%), choroidal/ciliary detachment (5.88%) and hypopyon (2.94%) were observed within 1wk. CONCLUSION: LCP is simple, safe, and effective in reforming the anterior chamber in malignant glaucoma.
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Subconjunctival fibrosis is the major cause of failure in both conventional and modern minimally invasive glaucoma surgeries (MIGSs) with subconjunctival filtration. The search for safe and effective anti-fibrotic agents is critical for improving long-term surgical outcomes. In this study, we investigated the effect of inhibiting the rapamycin-insensitive mTORC1/4E-BP1 axis on the transforming growth factor-beta 1(TGF-ß1)-induced fibrotic responses in human Tenon's fibroblasts (HTFs), as well as in a rat model of glaucoma filtration surgery (GFS). Primary cultured HTFs were treated with 3 ng/mL TGF-ß1 for 24 h, followed by treatment with 10 µM CZ415 for additional 24 h. Rapamycin (10 µM) was utilized as a control for mTORC1/4E-BP1 signaling insensitivity. The expression levels of fibrosis-associated molecules were measured using quantitative real-time PCR, Western blotting, and immunofluorescence analysis. Cell migration was assessed through the scratch wound assay. Additionally, a rat model of GFS was employed to evaluate the anti-fibrotic effect of CZ415 in vivo. Our findings indicated that both rapamycin and CZ415 treatment significantly reduced the TGF-ß1-induced cell proliferation, migration, and the expression of pro-fibrotic factors in HTFs. CZ415 also more effectively inhibited TGF-ß1-mediated collagen synthesis in HTFs compared to rapamycin. Activation of mTORC1/4E-BP signaling following TGF-ß1 exposure was highly suppressed by CZ415 but was only modestly inhibited by rapamycin. Furthermore, CZ415 was found to decrease subconjunctival collagen deposition in rats post GFS. Our results suggest that rapamycin-insensitive mTORC1/4E-BP1 signaling plays a critical role in TGF-ß1-driven collagen synthesis in HTFs. This study demonstrated that inhibition of the mTORC1/4E-BP1 axis offers superior anti-fibrotic efficacy compared to rapamycin and represents a promising target for improving the success rate of both traditional and modern GFSs.
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Proteínas Adaptadoras Transductoras de Señales , Fibroblastos , Fibrosis , Diana Mecanicista del Complejo 1 de la Rapamicina , Sirolimus , Cápsula de Tenon , Factor de Crecimiento Transformador beta1 , Animales , Factor de Crecimiento Transformador beta1/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/antagonistas & inhibidores , Humanos , Ratas , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Sirolimus/farmacología , Fibrosis/metabolismo , Cápsula de Tenon/metabolismo , Cápsula de Tenon/efectos de los fármacos , Células Cultivadas , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Movimiento Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Western Blotting , Ratas Sprague-Dawley , Proteínas de Ciclo Celular/metabolismo , Transducción de Señal , Reacción en Cadena en Tiempo Real de la Polimerasa , Masculino , Glaucoma/metabolismo , Glaucoma/tratamiento farmacológico , Glaucoma/patología , Inmunosupresores/farmacologíaRESUMEN
BACKGROUND: Neovascular glaucoma (NVG) is an irreversible blinding eye disease worldwide and is classified as one of the refractory glaucoma conditions, severely impacting visual function and vision. Unfortunately, effective surgical interventions to improve the prognosis of NVG patients are currently lacking. The study aims to evaluate the efficacy and safety of anterior chamber proliferative membrane interception (AC-PMI)-enhanced trabeculectomy compared to the traditional trabeculectomy. METHODS: AC-PMI enhanced trabeculectomy versus trabeculectomy for the treatment of NVG is a single-center, prospective, double-arms, and randomized controlled trial of superior efficacy, which will involve 100 NVG inpatients. Patients will be randomly assigned into two groups using the random number table method. One group will undergo trabeculectomy using anti-vascular endothelial growth factor (Anti-VEGF) preoperatively and mitomycin C intraoperatively, while the other group will undergo AC-PMI enhanced trabeculectomy with the same medications (Anti-VEGF and mitomycin C). The patients will be followed up at the baseline and 1 day, 1 week, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months postoperatively. Meanwhile, we will collect the demographics, characteristics, and examination results and monitor any occurrences of adverse events at each follow-up time. DISCUSSION: This is an efficacy study of a novel surgical approach for treating neovascular glaucoma. Building upon conventional filtering surgeries, this approach introduces an additional step involving the interception of the proliferative membrane to effectively halt the growth of fibrovascular tissue. This study aims to explore a promising new surgical approach for managing NVG and contribute to the advancement of glaucoma treatment strategies. TRIAL REGISTRATION: ChiCTR ChiCTR2200055138. Registered on 01 January 2022. https://www.chictr.org.cn/showproj.html?proj=145255.
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Glaucoma Neovascular , Ensayos Clínicos Controlados Aleatorios como Asunto , Trabeculectomía , Factor A de Crecimiento Endotelial Vascular , Humanos , Trabeculectomía/métodos , Trabeculectomía/efectos adversos , Glaucoma Neovascular/cirugía , Glaucoma Neovascular/fisiopatología , Estudios Prospectivos , Resultado del Tratamiento , Persona de Mediana Edad , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Anciano , Femenino , Masculino , Adulto , Cámara Anterior/cirugía , Presión Intraocular , Mitomicina/uso terapéutico , Mitomicina/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/administración & dosificación , Adulto JovenRESUMEN
Semi-supervised segmentation plays an important role in computer vision and medical image analysis and can alleviate the burden of acquiring abundant expert-annotated images. In this paper, we developed a residual-driven semi-supervised segmentation method (termed RDMT) based on the classical mean teacher (MT) framework by introducing a novel model-level residual perturbation and an exponential Dice (eDice) loss. The introduced perturbation was integrated into the exponential moving average (EMA) scheme to enhance the performance of the MT, while the eDice loss was used to improve the detection sensitivity of a given network to object boundaries. We validated the developed method by applying it to segment 3D Left Atrium (LA) and 2D optic cup (OC) from the public LASC and REFUGE datasets based on the V-Net and U-Net, respectively. Extensive experiments demonstrated that the developed method achieved the average Dice score of 0.8776 and 0.7751, when trained on 10% and 20% labeled images, respectively for the LA and OC regions depicted on the LASC and REFUGE datasets. It significantly outperformed the MT and can compete with several existing semi-supervised segmentation methods (i.e., HCMT, UAMT, DTC and SASS).
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AIM: To assess glaucoma patient satisfaction and follow-up adherence in case management and identify associated predictors to improve healthcare quality and patient outcomes. METHODS: In this cross-sectional study, a total of 119 patients completed a Patient Satisfaction Questionnaire-18 and a sociodemographic questionnaire. Clinical data was obtained from the case management system. Follow-up adherence was defined as completing each follow-up within ±30d of the scheduled time set by ophthalmologists during the study period. RESULTS: Average satisfaction scored 78.65±7, with an average of 4.39±0.58 across the seven dimensions. Age negatively correlated with satisfaction (P=0.008), whilst patients with follow-up duration of 2 or more years reported higher satisfaction (P=0.045). Multivariate logistics regression analysis revealed that longer follow-up durations were associated with lower follow-up adherence (OR=0.97, 95%CI, 0.95-1.00, P=0.044). Additionally, patients with suspected glaucoma (OR=2.72, 95%CI, 1.03-7.20, P=0.044) and those with an annual income over 100 000 Chinese yuan demonstrated higher adherence (OR=5.57, 95%CI, 1.00-30.89, P=0.049). CONCLUSION: The case management model proves effective for glaucoma patients, with positive adherence rates. The implementation of this model can be optimized in the future based on the identified factors and extended to glaucoma patients in more hospitals.
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BACKGROUND AND PURPOSE: Radiation-induced brain injury (RBI) is a severe radiotoxicity for nasopharyngeal carcinoma (NPC) patients, greatly affecting their long-term life quality and survival. We aim to establish a comprehensive predictive model including clinical factors and newly developed genetic variants to improve the precision of RBI risk stratification. MATERIALS AND METHODS: By performing a large registry-based retrospective study with magnetic resonance imaging follow-up on RBI development, we conducted a genome-wide association study and developed a polygenic risk score (PRS) for RBI in 1189 NPC patients who underwent intensity-modulated radiotherapy. We proposed a tolerance dose scheme for temporal lobe radiation based on the risk predicted by PRS. Additionally, we established a nomogram by combining PRS and clinical factors for RBI risk prediction. RESULTS: The 38-SNP PRS could effectively identify high-risk individuals of RBI (P = 1.42 × 10-34). Based on genetic risk calculation, the recommended tolerance doses of temporal lobes should be 57.6 Gy for individuals in the top 10 % PRS subgroup and 68.1 Gy for individuals in the bottom 50 % PRS. Notably, individuals with high genetic risk (PRS > P50) and receiving high radiation dose in the temporal lobes (D0.5CC > 65 Gy) had an approximate 50-fold risk over individuals with low PRS and receiving low radiation dose (HR = 50.09, 95 %CI = 24.27-103.35), showing an additive joint effect (Pinteraction < 0.001). By combining PRS with clinical factors including age, tumor stage, and radiation dose of temporal lobes, the predictive accuracy was significantly improved with C-index increased from 0.78 to 0.85 (P = 1.63 × 10-2). CONCLUSIONS: The PRS, together with clinical factors, could improve RBI risk stratification and implies personalized radiotherapy.
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Lesiones Encefálicas , Neoplasias Nasofaríngeas , Radioterapia de Intensidad Modulada , Humanos , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/patología , Estudios Retrospectivos , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/tratamiento farmacológico , Estudio de Asociación del Genoma Completo , Lesiones Encefálicas/etiología , Radioterapia de Intensidad Modulada/efectos adversos , Medición de RiesgoRESUMEN
Autoantibodies (AAbs) in the blood of colorectal cancer (CRC) patients have been evaluated for tumor detection. However, it remains uncertain whether these AAbs are specific to tumor-associated antigens. In this study, we explored the IgG and IgM autoantibody repertoires in both the in situ tissue microenvironment and peripheral blood as potential tumor-specific biomarkers. We applied high-density protein arrays to profile AAbs in the tumor-infiltrating lymphocyte supernatants and corresponding serum from four patients with CRC, as well as in the serum of three noncancer controls. Our findings revealed that there were more reactive IgM AAbs than IgG in both the cell supernatant and corresponding serum, with a difference of approximately 3-5 times. Immunoglobulin G was predominant in the serum, while IgM was more abundant in the cell supernatant. We identified a range of AAbs present in both the supernatant and the corresponding serum, numbering between 432 and 780, with an average of 53.3% shared. Only 4.7% (n = 23) and 0.2% (n = 2) of reactive antigens for IgG and IgM AAbs, respectively, were specific to CRC. Ultimately, we compiled a list of 19 IgG AAb targets as potential tumor-specific AAb candidates. Autoantibodies against one of the top candidates, p15INK4b-related sequence/regulation of nuclear pre-mRNA domain-containing protein 1A (RPRD1A), were significantly elevated in 53 CRC patients compared to 119 controls (p < 0.0001). The project revealed that tissue-derived IgG AAbs, rather than IgM, are the primary source of tumor-specific AAbs in peripheral blood. It also identified potential tumor-specific AAbs that could be applied for noninvasive screening of CRC.
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Autoanticuerpos , Neoplasias Colorrectales , Humanos , Biomarcadores de Tumor , Inmunoglobulina G , Inmunoglobulina M , Microambiente Tumoral , Proteínas Represoras , Proteínas de Ciclo CelularRESUMEN
AIM: To describe the outcome of using low-dose laser cycloplasty (LCP) in chronic angle-closure glaucoma (CACG). METHODS: A retrospective case series. Medical charts of CACG patients who underwent LCP in the Eye Hospital of Wenzhou Medical University were reviewed. The main outcomes included intraocular pressure (IOP), the number of glaucoma medication, anterior segment parameters and surgery-related complications. RESULTS: A total of 7 eyes of 7 CACG patients (age 38.9±11.0y) underwent LCP with a mean follow-up of 27.1±13.7mo (range 16-48mo). Following LCP, mean IOP and glaucoma medications decreased from 26.1±6.1 mm Hg with 3.1±1.1 glaucoma medications pre-treatment to 14.9±3.1 mm Hg (P=0.027) with 0.4±1.1 glaucoma medications (P=0.001) at final follow-up. The anterior chamber depth (ACD), angle opening distance500 and trabecular-iris angle increased from 1.65±0.33 mm, 0.05 mm (range 0-0.30 mm) and 5.1° (range, 0-31.97°) at baseline to 1.98±0.43 mm (P=0.073), 0.53 mm (range 0.42-0.91 mm, P=0.015), 45.9° (range, 40.2°-59.4°, (P=0.015) in the long-term follow-up, respectively. The deepening of ACD and reopening of anterior chamber angle (ACA) was observed in 6 eyes (85.7%). CONCLUSION: LCP is a promising treatment option for patients with CACG via reducing IOP and glaucoma medication without serious complications. In addition, LCP can bring a significant deepening in ACD and reopening of ACA.
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Previous studies have demonstrated strong associations between host genetic factors and Epstein-Barr virus (EBV) VCA-IgA with the risk of nasopharyngeal carcinoma (NPC). However, the specific interplay between host genetics and EBV VCA-IgA on NPC risk is not well understood. In this two-stage case-control study (N = 4804), we utilized interaction and mediation analysis to investigate the interplay between host genetics (genome-wide association study-derived polygenic risk score [PRS]) and EBV VCA-IgA antibody level in the NPC risk. We employed a four-way decomposition analysis to assess the extent to which the genetic effect on NPC risk is mediated by or interacts with EBV VCA-IgA. We consistently found a significant interaction between the PRS and EBV VCA-IgA on NPC risk (discovery population: synergy index [SI] = 2.39, 95% confidence interval [CI] = 1.85-3.10; replication population: SI = 3.10, 95% CI = 2.17-4.44; all pinteraction < 0.001). Moreover, the genetic variants included in the PRS demonstrated similar interactions with EBV VCA-IgA antibody. We also observed an obvious dose-response relationship between the PRS and EBV VCA-IgA antibody on NPC risk (all ptrend < 0.001). Furthermore, our decomposition analysis revealed that a substantial proportion (approximately 90%) of the genetic effects on NPC risk could be attributed to host genetic-EBV interaction, while the risk effects mediated by EBV VCA-IgA antibody were weak and statistically insignificant. Our study provides compelling evidence for an interaction between host genetics and EBV VCA-IgA antibody in the development of NPC. These findings emphasize the importance of implementing measures to control EBV infection as a crucial strategy for effectively preventing NPC, particularly in individuals at high genetic risk.
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Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Herpesvirus Humano 4/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/genética , Neoplasias Nasofaríngeas/genética , Estudios de Casos y Controles , Estudio de Asociación del Genoma Completo , Anticuerpos Antivirales/genética , Proteínas de la Cápside/genética , Antígenos Virales/genética , Inmunoglobulina ARESUMEN
Inherited retinal dystrophies (IRDs) are a heterogeneous group of visual disorders caused by different pathogenic mutations in genes and regulatory sequences. The endoplasmic reticulum (ER) membrane protein complex (EMC) subunit 3 (EMC3) is the core unit of the EMC insertase that integrates the transmembrane peptides into lipid bilayers, and the function of its cytoplasmic carboxyl terminus remains to be elucidated. In this study, an insertional mutation c.768insT in the C-terminal coding region of EMC3 was identified and associated with dominant IRDs in a five-generation family. This mutation caused a frameshift in the coding sequence and a gain of an additional 16 amino acid residues (p.L256F-fs-ext21) to form a helix structure in the C-terminus of the EMC3 protein. The mutation is heterozygous with an incomplete penetrance, and cosegregates in all patients examined. This finding indicates that the C-terminus of EMC3 is essential for EMC functions and that EMC3 may be a novel candidate gene for retinal degenerative diseases.
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BACKGROUND: Clostridioides difficile (C. difficile) is the major pathogen causing antibiotic-associated diarrhea. There are a variety of symptoms associated with C. difficile infection (CDI) in adults, including self-limiting diarrhea, pseudomembranous colitis, toxic megacolon, septic shock, and even death from the infection. However, the infant's intestine appears to be completely resistant to the effects of C. difficile toxins A and B with rare development of clinical symptoms. CASE PRESENTATION: In this study, we reported a 1-month-old girl with CDI who was born with neonatal hypoglycemia and necrotizing enterocolitis. Her symptom of diarrhea occurred after extensive use of broad-spectrum antibiotics during hospitalization and was accompanied by elevated white blood cell, platelet, and C-reactive protein levels, and repeated routine stool examinations were abnormal. She was recovered by norvancomycin (an analogue of vancomycin) and probiotic treatment. The results of 16 S rRNA gene sequencing also demonstrated the recovery of intestinal microbiota with the enrichment of Firmicutes and Lactobacillus. CONCLUSIONS: Based on the literature review and this case report, clinicians should also pay attention to diarrhea caused by C. difficile in infants and young children. More strong evidence is needed to explain the true prevalence of CDI in this population and to better understand the C. difficile-associated diarrhea in infants.
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Large-scale genetic association studies have identified multiple susceptibility loci for nasopharyngeal carcinoma (NPC), but the underlying biological mechanisms remain to be explored. To gain insights into the genetic etiology of NPC, we conducted a follow-up study encompassing 6,907 cases and 10,472 controls and identified two additional NPC susceptibility loci, 9q22.33 (rs1867277; OR = 0.74, 95% CI = 0.68-0.81, p = 3.08 × 10-11) and 17q12 (rs226241; OR = 1.42, 95% CI = 1.26-1.60, p = 1.62 × 10-8). The two additional loci, together with two previously reported genome-wide significant loci, 5p15.33 and 9p21.3, were investigated by high-throughput sequencing for chromatin accessibility, histone modification, and promoter capture Hi-C (PCHi-C) profiling. Using luciferase reporter assays and CRISPR interference (CRISPRi) to validate the functional profiling, we identified PHF2 at locus 9q22.33 as a susceptibility gene. PHF2 encodes a histone demethylase and acts as a tumor suppressor. The risk alleles of the functional SNPs reduced the expression of the target gene PHF2 by inhibiting the enhancer activity of its long-range (4.3 Mb) cis-regulatory element, which promoted proliferation of NPC cells. In addition, we identified CDKN2B-AS1 as a susceptibility gene at locus 9p21.3, and the NPC risk allele of the functional SNP rs2069418 promoted the expression of CDKN2B-AS1 by increasing its enhancer activity. The overexpression of CDKN2B-AS1 facilitated proliferation of NPC cells. In summary, we identified functional SNPs and NPC susceptibility genes, which provides additional explanations for the genetic association signals and helps to uncover the underlying genetic etiology of NPC development.
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Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Estudios de Asociación Genética , Polimorfismo de Nucleótido Simple/genética , Proteínas de Homeodominio/genéticaRESUMEN
BACKGROUND: To report the incidence and clinical characteristics of aqueous misdirection (AM) after glaucoma surgery in Chinese patients with primary angle-closure glaucoma. METHODS: Medical records of all patients diagnosed with primary angle-closure glaucoma who underwent glaucoma surgery in the Eye Hospital of Wenzhou Medical University between January 2012 and December 2021 were retrospectively reviewed. Cases of AM were identified through a keyword-based search. The incidence of AM was calculated. Demographic and clinical characteristics of the AM patients were also described. RESULTS: A total of 5044 eyes with primary angle-closure glaucoma were included (mean age 65.81 ± 9.96 years, 68.11% women). Thirty-eight eyes developed AM, presenting an overall incidence of 0.75%. The mean time interval between surgery and first record of AM diagnosis was 2.57 ± 5.24 months (range, 0 day to 24 months). The incidence of AM was significantly higher in patients aged ≤ 40 years (21.28%) and those aged 40-50 years (3.32%), compared to those > 50 years (0.42%) (P < 0.001). AM developed much more frequently among patients with chronic angle-closure glaucoma (1.30%), compared to those with acute angle-closure glaucoma (0.32%, P < 0.001). Eleven eyes (0.37%) developed AM following non-filtering surgery compared to 24 eyes (2.27%) after filtering surgery (P < 0.001). CONCLUSION: The incidence of AM after glaucoma surgery was 0.75% in Chinese patients with primary angle closure glaucoma. Younger age, chronic angle-closure glaucoma, and undergoing filtering surgery, were identified as associated risk factors for developing AM. Phacoemulsification may have less risk of developing AM compared to filtering surgery.
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Human leukocyte antigen (HLA) molecules are essential for presenting Epstein-Barr virus (EBV) antigens and are closely related to nasopharyngeal carcinoma (NPC). This study aims to systematically investigate the association between HLA-bound EBV peptides and NPC risk through in silico HLA-peptide binding prediction. A total of 455 NPC patients and 463 healthy individuals in NPC endemic areas were recruited, and HLA-target sequencing was performed. HLA-peptide binding prediction for EBV, followed by peptidome-wide logistic regression and motif analysis, was applied. Binding affinity changes for EBV peptides carrying high-risk mutations were analyzed. We found that NPC-associated EBV peptides were significantly enriched in immunogenic proteins and core linkage disequilibrium (LD) proteins related to evolution, especially those binding HLA-A alleles (p = 3.10 × 10-4 for immunogenic proteins and p = 8.10 × 10-5 for core LD proteins related to evolution). These peptides were clustered and showed binding motifs of HLA supertypes, among which supertype A02 presented an NPC-risk effect (padj = 3.77 × 10-4 ) and supertype A03 presented an NPC-protective effect (padj = 4.89 × 10-4 ). Moreover, a decreased binding affinity toward risk HLA supertype A02 was observed for the peptide carrying the NPC-risk mutation BNRF1 V1222I (p = 0.0078), and an increased binding affinity toward protective HLA supertype A03 was observed for the peptide carrying the NPC-risk mutation BALF2 I613V (p = 0.022). This study revealed the distinct preference of EBV peptides for binding HLA supertypes, which may contribute to shaping EBV population structure and be involved in NPC development.
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Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Epítopos , Herpesvirus Humano 4/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/genética , Carcinoma Nasofaríngeo/genética , Antígenos de Histocompatibilidad Clase II , Neoplasias Nasofaríngeas/genéticaRESUMEN
INTRODUCTION: The aim of this study was to compare the patterns of visual field (VF) defects in primary angle-closure glaucoma (PACG) to control groups of eyes with high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). METHODS: Forty-eight eyes with PACG were enrolled, and control eyes with HTG and NTG matched for age, sex, and mean deviation of VF defect were selected. VF tests were performed using the 24-2 program of the Humphrey field analyzer. VF defects were classified into six patterns with the Ocular Hypertension Treatment Study classification system and were categorized into three stages (early, moderate, and advanced). Each hemifield was divided into five regions according to the Glaucoma Hemifield Test (GHT). The mean total deviation (TD) of each GHT region was calculated. RESULTS: Compared with HTG and NTG groups, the partial arcuate VF defects were more common in the PACG group. In the PACG group, the nasal GHT region in the inferior hemifield had the worst mean TD (-8.48 ± 8.62 dB), followed by the arcuate 1 (-7.81 ± 7.91 dB), arcuate 2 (-7.46 ± 7.43 dB), paracentral (-7.19 ± 7.98 dB), and central (-5.14 ± 6.24 dB) regions; the mean TD of the central region was significantly better than those for all other regions (all p < 0.05). A similar trend was observed in the superior hemifield in the PACG group but not the VF hemifields of the HTG and NTG groups. CONCLUSION: Patterns of VF defect in PACG patients differ from those with HTG and NTG. This discrepancy might be due to the differences in the pathogenic mechanisms of glaucomatous optic neuropathy.
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Glaucoma de Ángulo Cerrado , Glaucoma de Ángulo Abierto , Glaucoma , Glaucoma de Baja Tensión , Humanos , Campos Visuales , Glaucoma de Ángulo Abierto/complicaciones , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/patología , Presión Intraocular , Glaucoma/patología , Glaucoma de Baja Tensión/diagnóstico , Pruebas del Campo Visual , Trastornos de la Visión , Células Ganglionares de la Retina/patologíaRESUMEN
PRCIS: Faster hemispheric mVD loss was found in the affected hemifield of POAG patients without significant changes in hemispheric thickness. The progression of mVD loss was associated with the severity of VF damage. PURPOSE: To evaluate the changes in macular vessel density (mVD) loss in primary open angle glaucoma (POAG) patients with visual field (VF) defects confined to 1 hemifield. MATERIALS AND METHODS: This longitudinal cohort study used linear mixed models to evaluate the changes in the hemispheric mean total deviation (mTD), mVD, macular ganglion cell complex, macular ganglion cell-inner plexiform layer, and retinal nerve fiber layer between affected hemifields, unaffected hemifields, and healthy controls. RESULTS: Twenty-nine POAG eyes and 25 healthy eyes were followed for an average of 29 months. In POAG eyes, the rates of decline in hemispheric mTD and hemispheric mVD in the affected hemifields were significantly faster than those in the unaffected hemifields (-0.42±1.24 vs. 0.02±0.69 dB/year, P =0.018 and -2.16±1.01 vs. -1.77±0.90% / year, P =0.031, respectively). There were no differences in the rate of hemispheric thickness change between the 2 hemifields. The rate of hemispheric mVD decline in both hemifields of POAG eyes was significantly faster than that of the healthy controls (All P <0.05). An association between the reduced mTD of the VF and the rate of hemispheric mVD loss in the affected hemifield was observed (r=0.484, P =0.008). Faster rates of mVD loss (ß=-1.72±0.80, P =0.050) were significantly related to reduced hemispheric mTD in the multivariate analysis. CONCLUSIONS: Faster hemispheric mVD loss was found in the affected hemifield of POAG patients without significant changes in hemispheric thickness. The progression of mVD loss was associated with the severity of VF damage.
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Glaucoma de Ángulo Abierto , Glaucoma , Disco Óptico , Humanos , Campos Visuales , Glaucoma de Ángulo Abierto/diagnóstico , Tomografía de Coherencia Óptica/métodos , Estudios Longitudinales , Vasos Retinianos , Presión Intraocular , Células Ganglionares de la Retina , Trastornos de la Visión/diagnóstico , AngiografíaRESUMEN
Chemoradiation-induced hearing loss (CRIHL) is one of the most devasting side effects for nasopharyngeal carcinoma (NPC) patients, which seriously affects survivors' long-term quality of life. However, few studies have comprehensively characterized the risk factors for CRIHL. In this study, we found that age at diagnosis, tumor stage, and concurrent cisplatin dose were positively associated with chemoradiation-induced hearing loss. We performed a genome-wide association study (GWAS) in 777 NPC patients and identified rs1050851 (within the exon 2 of NFKBIA), a variant with a high deleteriousness score, to be significantly associated with hearing loss risk (HR = 5.46, 95% CI 2.93-10.18, P = 9.51 × 10-08). The risk genotype of rs1050851 was associated with higher NFKBIA expression, which was correlated with lower cellular tolerance to cisplatin. According to permutation-based enrichment analysis, the variants mapping to 149 hereditary deafness genes were significantly enriched among GWAS top signals, which indicated the genetic similarity between hereditary deafness and CRIHL. Pathway analysis suggested that synaptic signaling was involved in the development of CRIHL. Additionally, the risk score integrating genetic and clinical factors can predict the risk of hearing loss with a relatively good performance in the test set. Collectively, this study shed new light on the etiology of chemoradiation-induced hearing loss, which facilitates high-risk individuals' identification for personalized prevention and treatment.
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Sordera , Pérdida Auditiva , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Cisplatino/efectos adversos , Estudio de Asociación del Genoma Completo , Calidad de Vida , Pérdida Auditiva/inducido químicamente , Pérdida Auditiva/genética , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/inducido químicamenteRESUMEN
PURPOSE: To evaluate the surgical outcomes in patients with Posner-Schlossman syndrome (PSS) at one year. METHODS: A prospective interventional study in PSS patients with penetrating canaloplasty. Main outcome measure was success rate (6 mmHg≤ intraocular pressure (IOP) ≤ 21 mmHg) with or without medications. RESULTS: Thirteen eyes in 13 patients with PSS underwent complete catheterization. The mean IOP and medications (Meds) were reduced to 16.1 ± 4.8 mmHg on 0.5 ± 1.0 Meds at 12 months. Complete and qualified success rates were 61.5% and 84.6% at 12 months. The postoperative recurrent rate of PSS was 69.2%, the mean peak IOP during attacks and episodes were decreased to 26.7 ± 8.3 mmHg and 1.7 ± 2.0 times respectively. Transient IOP spike (61.5%) and hyphema (38.5%) were the two most common postoperative complications. CONCLUSION: Penetrating canaloplasty achieves a high success rate in PSS without serious complications.
RESUMEN
AIM: To evaluate the trend of glaucoma internal filtration surgeries for inpatients between 2015 and 2021 at the Eye Hospital of Wenzhou Medical University. METHODS: A review of the medical records of inpatients who had been diagnosed with glaucoma and received anti-glaucoma surgery between January 1, 2015 and December 31, 2021 was conducted. The glaucoma diagnosis in this study included primary open angle glaucoma, primary angle-closure glaucoma, secondary glaucoma, and paediatric glaucoma. The types of surgeries were categorised as internal filtration, external filtration, and cyclodestruction surgery based on the pathway of aqueous humor outflow. The trend of these glaucoma surgeries in the sample of patients with different types of glaucoma was then analysed. RESULTS: The number of patients hospitalised for glaucoma surgery increased yearly, from 752 in 2015 to 1373 in 2021, at the Eye Hospital of Wenzhou Medical University. Regarding the patients diagnosed with primary open angle glaucoma, internal filtration surgery increased from 27.40% of the sample to 54.40% of the sample, while external filtration surgery decreased from 71.50% to 44.20% between 2015 and 2021. For paediatric glaucoma, internal filtration surgery increased from 37.50% in 2015 to 88.20% in 2021. Whilst different types of surgeries were performed on the sample of patients with secondary glaucoma, the proportion of internal filtration surgery also showed an increase from 18.20% in 2015 to 40.90% in 2021. Meanwhile, internal filtration surgery in the patient sample with primary angle-closure glaucoma already accounted for over 70.00% in 2015, and showed a small increase by 2021. CONCLUSION: As surgical technology and surgical experience continue to elevate and improve, the range of glaucoma surgeries are correspondingly evolving. This study find that internal filtration surgeries accounted for an increasing proportion of treatments in the surgical management of glaucoma between 2015 and 2021.