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BACKGROUND/AIMS: The aims of this study is to evaluate the anatomic, visual outcomes and associated prognostic factors in patients with advanced retinopathy of prematurity (ROP) following vitrectomy. METHODS: A retrospective cohort study of patients with ROP who underwent vitrectomy from 2005 to 2016 was conducted. All the patients had a follow-up period of at least 5 years. Univariate and multivariable logistic regression analyses were used to explore the factors related to unfavourable outcomes. RESULTS: In total, 81 eyes of 51 patients were included. The mean age at last follow-up was 10.2 years. The anatomic success rate was 96.3% (26/27) for stage 4A, 90.9% (20/22) for stage 4B and 31.3% (10/32) for stage 5 ROP (p<0.01). The mean logMAR best corrected visual acuity of the stage-4A eyes was the highest, followed by those of stage-4B and stage-5 eyes (0.8, 1.5 and 2.6 for stages 4A, 4B and 5, respectively; p<0.01). High myopia (≤ -5.0 D) was noted in 70.8% and 71.4% of stage-4A and stage-4B eyes, respectively. Cataract was the most common complication (25.9%), followed by corneal opacity (17.3%), strabismus (16.1%), and phthisis (16.1%). Stage of the disease was a poor prognostic factor in all vitrectomised eyes (p<0.01). Vitrectomy combined lensectomy was a significant predictor for poor anatomic outcomes for stage-4 eyes (p=0.03). Presence of plus disease was also a possible factor affecting the surgical outcomes. CONCLUSION: The long-term surgical outcomes of the eyes with stage 4A and 4B ROP were favourable. Management of stage 5 ROP remained challenging.
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PURPOSE: To characterize patients with cytomegalovirus (CMV) retinitis and identify risk factors for retinal detachment (RD) and mortality in this Taiwanese patient population. METHODS: This retrospective study included patients diagnosed with CMV retinitis between 2007 and 2019. The diagnosis was confirmed through aqueous polymerase chain reaction (PCR). Relevant data were collected from the Chang Gung Research Database. Univariate Cox regression was performed to identify the associations of RD and mortality risks with various patient characteristics, including demographic features, comorbidities, laboratory results, and medication use patterns. RESULTS: In total, 32 patients with CMV retinitis were included. Among these patients, 78.1% had an immunocompromised status, including 56.3% with high-dose systemic steroid use, 21.9% with HIV infection, 12.5% with hematologic malignancy, and 9.4% with renal transplantation. Approximately 21.9% of patients had RD 2.4 ± 2.1 months after CMV retinitis diagnosis, and 34.4% died within 6.2 [4.2, 38.2] months after diagnosis. Patients with RD had a statistically significant, but likely not clinically significant, later initiation of anti-CMV medications compared to their non-RD counterparts (8 [5, 23] days vs. 2 [1, 11] days, p = 0.039). Mortality was significantly associated with older age (hazard ratio [HR]: 1.06; 95% confidence interval [CI]: 1.02-1.10), hematologic malignancy (HR: 5.92; 95% CI: 1.44-24.37), and positivity for CMV on blood PCR (HR: 4.93; 95% CI: 1.49-16.35). CONCLUSION: Our study suggests that older age, hematologic malignancy, and positivity for CMV on blood PCR are risk factors for mortality in patients with CMV retinitis. KEY MESSAGES: What is known Cytomegalovirus (CMV) retinitis is the predominant sight-threatening opportunistic ocular infection in patients with acquired immunodeficiency syndrome (AIDS). What is new In the era of highly active antiretroviral therapy for AIDS, the majority of CMV retinitis patients are those receiving immunomodulatory therapy for underlying diseases. Older age, hematologic malignancy, and positive blood polymerase chain reaction for CMV are potential risk factors for mortality in patients with CMV retinitis.
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Extracellular vesicles play an important role in the progression of pancreatic adenocarcinoma (PAAD) through the transfer of proteins, mRNAs, and long noncoding RNAs (lncRNAs). However, the intricate interplay between extracellular vesicles-related lncRNAs and the tumor microenvironment (TME) remains poorly elucidated. Consequently, our investigation aimed to delineate the association between extracellular vesicles-related lncRNAs and the PAAD microenvironment. Initially, we identified differentially expressed lncRNAs (DELs) from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) project datasets. Subsequently, we validated the expression of these DELs within extracellular vesicles and assessed their prognostic implications in PAAD using the GSE133684 and TCGA datasets. Multiomics data were analyzed comprehensively, including genomic landscape, functional annotation, immune profiles, and therapeutic responses. Differential expression of selected lncRNAs in both cellular and exosomal fractions of PAAD was further confirmed through quantitative polymerase chain reaction (qPCR). Eight DELs were identified from TCGA and GTEx datasets, and two exosomal lncRNAs exhibited a significant correlation with overall survival, warranting further investigation. Specifically, elevated expression of LINC00996 correlated positively with immune infiltration and enhanced response to immunotherapy. Conversely, heightened expression of TRHED-AS1 was associated with compromised immune cell infiltration and diminished responsiveness to immunotherapy. Our study establishes a compelling link between two extracellular vesicles-related gene signatures, prognosis, and immune infiltration in PAAD. Notably, these signatures serve as robust prognostic indicators for PAAD patients, offering valuable insights for the strategic selection of immunotherapeutic interventions.
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Adenocarcinoma , Vesículas Extracelulares , Neoplasias Pancreáticas , RNA Longo não Codificante , Microambiente Tumoral , Humanos , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/terapia , Vesículas Extracelulares/metabolismo , Microambiente Tumoral/imunologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Adenocarcinoma/imunologia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/terapia , Prognóstico , Regulação Neoplásica da Expressão GênicaRESUMO
The pathogenesis of ankylosing spondylitis (AS) remains unclear, and while recent studies have implicated necroptosis in various autoimmune diseases, an investigation of its relationship with AS has not been reported. In this study, we utilized the Gene Expression Omnibus database to compare gene expressions between AS patients and healthy controls, identifying 18 differentially expressed necroptosis-related genes (DENRGs), with 8 upregulated and 10 downregulated. Through the application of three machine learning algorithms-least absolute shrinkage and selection operation, support vector machine-recursive feature elimination and random forest-two hub genes, FASLG and TARDBP, were pinpointed. These genes demonstrated high specificity and sensitivity for AS diagnosis, as evidenced by receiver operating characteristic curve analysis. These findings were further supported by external datasets and cellular experiments, which confirmed the downregulation of FASLG and upregulation of TARDBP in AS patients. Immune cell infiltration analysis suggested that CD4+ T cells, CD8+ T cells, NK cells and neutrophils may be associated with the development of AS. Notably, in the group with high FASLG expression, there was a significant infiltration of CD8+ T cells, memory-activated CD4+ T cells and resting NK cells, with relatively less infiltration of memory-resting CD4+ T cells and neutrophils. Conversely, in the group with high TARDBP expression, there was enhanced infiltration of naïve CD4+ T cells and M0 macrophages, with a reduced presence of memory-resting CD4+ T cells. In summary, FASLG and TARDBP may contribute to AS pathogenesis by regulating the immune microenvironment and immune-related signalling pathways. These findings offer new insights into the molecular mechanisms of AS and suggest potential new targets for therapeutic strategies.
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Biologia Computacional , Necroptose , Espondilite Anquilosante , Espondilite Anquilosante/genética , Espondilite Anquilosante/patologia , Humanos , Biologia Computacional/métodos , Necroptose/genética , Perfilação da Expressão Gênica , Proteína Ligante Fas/genética , Proteína Ligante Fas/metabolismo , Regulação da Expressão Gênica , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Redes Reguladoras de Genes , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Curva ROC , Bases de Dados GenéticasRESUMO
PURPOSE: To evaluate choroidal changes over time in school-age children with a history of prematurity. METHODS: A study of 416 eyes of 208 eligible participants, including 88, 190, 36, 56, and 46 eyes in the full-term control, preterm, spontaneously regressed retinopathy of prematurity, intravitreal bevacizumab (injection of bevacizumab)-treated retinopathy of prematurity, and laser-treated retinopathy of prematurity groups, respectively, were enrolled in this study. The choroidal thickness was measured 4 times at 6-month intervals using optical coherence tomography. RESULTS: Of all the groups, the laser-treated children had the thinnest choroid compared with full-term children (-52.3 µ m, P = 0.04). Preterm children exhibited greater attenuation in choroidal thickness over time than did full-term children (-6.3 ± 26.9 and -1.1 ± 12.8 µ m/year, P = 0.03), whereas no difference was observed between injection of bevacizumab and laser treatments (-4.6 ± 18.9 and -2.0 ± 15.7 µ m/year, P = 0.46). In all groups, the changes in axial length were negatively associated with the changes in choroidal thickness (all P < 0.05). CONCLUSION: A greater attenuation in choroid thickness over time was observed in preterm children than in full-term children, but this attenuation did not differ between injection of bevacizumab and laser treatments. Axial elongation was associated with choroidal thinning in school-age children.
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Inibidores da Angiogênese , Bevacizumab , Corioide , Idade Gestacional , Injeções Intravítreas , Retinopatia da Prematuridade , Tomografia de Coerência Óptica , Humanos , Corioide/patologia , Corioide/diagnóstico por imagem , Estudos Prospectivos , Masculino , Tomografia de Coerência Óptica/métodos , Feminino , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Criança , Bevacizumab/administração & dosagem , Seguimentos , Recém-Nascido , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Recém-Nascido Prematuro , Fotocoagulação a Laser/métodos , Acuidade VisualRESUMO
Complicated fractures have always been challenging in orthopaedics. Designing a multifunctional biomaterial that can contribute to the treatment of fractures using a simple operation remains challenging. Here, we developed a trinity hydrogel system consisting of hydrogel prepared from phenylboronic acid modified gelatin and oxidized-dextran, lithium and cobalt co-doped mesoporous bioactive glass nanoparticles (MBGNs), and irisin. This hydrogel material exhibits considerable injectability, fat-to-shape, and self-healing characteristics. In addition, compared to hydrogel prepared from gelatin and oxidized-dextran, the hydrogel material presented a noticeable enhancement in compression stress and adhesion strength towards porcine bone fragments, which enables it more effectively splice bone fragments during surgery. Based on the various interactions between irisin and the hydrogel network, the system exhibited a clear sustained release of irisin. Based on the results of in vitro cell tests, the hydrogel material showed good cytocompatibility. And it also considerably enhanced the in vitro pro-osteogenic and pro-angiogenic capacities of bone marrow mesenchymal stromal cells (BMSCs) and human umbilical vein endothelial cells (HUVECs). In vivo experimental results indicated that this hydrogel considerably improved the repair of cranial defects in rats. The current study provides a feasible strategy for the treatment of bone fractures and stimulation of fracture healing.
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Ácidos Borônicos , Hidrogéis , Engenharia Tecidual , Ratos , Humanos , Animais , Suínos , Engenharia Tecidual/métodos , Hidrogéis/farmacologia , Gelatina/farmacologia , Dextranos/farmacologia , Fibronectinas , Osteogênese , Células Endoteliais da Veia Umbilical HumanaRESUMO
Objective: The immune response assumes a pivotal role in the underlying mechanisms of urticaria pathogenesis. The present study delves into an investigation of the genetic causal connections between urticaria and prevalent autoimmune afflictions, notably rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ulcerative colitis (UC), and Crohn's disease (CD). Methods: A bidirectional two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationships involving four autoimmune diseases and urticaria. The genome-wide association study (GWAS) summary data of four autoimmune disease were sourced from the IEU OpenGWAS database. The GWAS summary data for urticaria were derived from the Finnish consortium dataset. The principal analytical approach employed in this study was the random-effects inverse variance weighted (IVW) method. Subsequently, a series of sensitivity analyses were performed, encompassing assessments of heterogeneity, horizontal pleiotropy, outliers, "Leave-one-out" analyses, and tests for adherence to the assumption of normal distribution. Results: The random-effects IVW analysis indicate a positive genetic causal association between RA and urticaria (P < 0.001, OR 95% CI = 1.091 [1.051-1.133]). Conversely, SLE, UC, and CD do not exhibit a significant genetic causal relationship with urticaria. The reverse MR analysis reveals a positive genetic causal linkage between urticaria and SLE (P = 0.026, OR 95% CI = 1.289 [1.031-1.612]). However, the analysis demonstrates no substantial genetic causal relationship between urticaria and RA, UC, or CD. Importantly, the genetic causal assessment absence of heterogeneity, horizontal pleiotropy, and outliers. Furthermore, it remains unaffected by any individual single nucleotide polymorphism (SNP), demonstrating adherence to a normal distribution. Conclusion: This investigation establishing RA as a predisposing factor for urticaria. Moreover, urticaria as a plausible risk determinant for SLE. Heightened vigilance is recommended among RA patients to monitor the manifestation of urticaria within clinical settings. Similarly, individuals afflicted by urticaria should duly acknowledge the prospective susceptibility to SLE.
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Artrite Reumatoide , Doenças Autoimunes , Colite Ulcerativa , Doença de Crohn , Lúpus Eritematoso Sistêmico , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Estudos Prospectivos , Doenças Autoimunes/genética , Artrite Reumatoide/genética , Lúpus Eritematoso Sistêmico/genética , Causalidade , Colite Ulcerativa/genética , Doença de Crohn/genéticaRESUMO
Purpose: This study investigated the associations between vascular endothelial growth factor (VEGF) polymorphisms and retinopathy of prematurity (ROP) risk. Methods: Infants born prematurely at any time from 2009 to 2018 were included. Five single-nucleotide polymorphisms (SNPs) of VEGF were analyzed using real-time PCR in all infants. Multivariate logistic regression was applied to model the associations between VEGF polymorphisms and ROP susceptibility, severity, and premature clinicopathologic characteristics. Results: A total of 334 patients were included and categorized into three groups: those without ROP, those with mild ROP (i.e., ROP not requiring treatment), and those with severe ROP (i.e., ROP for whom treatment was indicated). Among the female patients with ROP, those with VEGF rs3025035 CT (3.231-fold; 95% confidence interval [CI], 1.238-8.431) and a combination of CT and TT genotypes (2.643-fold; 95% CI, 1.056-6.619) exhibited significantly higher risks of severe ROP compared with those with wild-type genotypes. Female ROP infants with VEGF rs3025010 C (TC + CC) alleles had a lower risk of ROP stage ≥3 (odds ratio [OR] = 0.406; 95% CI, 0.165-0.999) than those with TT homozygotes. ROP patients with the VEGF rs10434 A allele (GA + AA) exhibited higher risks of necrotizing enterocolitis (OR = 2.750; 95% CI, 1.119-6.759) and lower risk of bronchopulmonary dysplasia (OR = 0.390; 95% CI, 0.173-0.877) than those with GG homozygotes did. Conclusions: VEGF polymorphisms affect ROP risks differently in male and female infants. In female infants, VEGF rs3025035 with T alleles may predict ROP severity, and VEGF rs3025010 with C alleles may protect against severe ROP.
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Retinopatia da Prematuridade , Fator A de Crescimento do Endotélio Vascular , Humanos , Recém-Nascido , Nascimento Prematuro , Fator A de Crescimento do Endotélio Vascular/genética , Retinopatia da Prematuridade/genéticaRESUMO
This study aims to investigate the outcomes and risk factors associated with poor vision (vision less than counting fingers, 2.0 logMAR, Snellen vision 20/2000) in patients with posterior or combined persistent fetal vasculature (PFV), with or without surgery. We retrospectively reviewed the medical records of patients who were diagnosed with PFV from January 2008 to April 2021. We included 51 eyes of 44 patients who presented with PFV, of which 38 eyes underwent surgical correction (pars plicata/plana vitrectomy, with or without lensectomy, and intraocular lens implantation) at the median age of 6.0 months (range: 0.7 to 82.0). The mean follow-up was 68.8 months ± 38.0 months. The axial length change in the eyes undergoing surgery was significantly higher than the eyes without surgery (p = 0.025). Initial anterior chamber collapse and retinal detachment were associated with poor vision (p = 0.006 and p = 0.002, respectively). In addition, 37% of eyes with posterior or combined PFV had vision better than counting fingers. Surgery for eyes with PFV could result in better eye growth. Visual outcomes remained poor and were associated with the level of macular abnormality. Initial anterior chamber collapse and retinal detachment at presentation were the risk factors for poor visual outcomes. Vitrectomy for selected PFV eyes is valuable and associated with a better cosmetic outcome (better eye growth).
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Vítreo Primário Hiperplásico Persistente , Descolamento Retiniano , Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Estudos Retrospectivos , Vítreo Primário Hiperplásico Persistente/diagnóstico , Vítreo Primário Hiperplásico Persistente/cirurgia , Vitrectomia , Resultado do Tratamento , Complicações Pós-OperatóriasRESUMO
The clinical benefits of diquafosol tetrasodium (DQS), a hydrophilic P2Y2 receptor agonist for dry eye, have been hindered by a demanding dosing regimen. Nevertheless, it is challenging to achieve sustained release of DQS with conventional drug delivery vehicles which are mainly designed for hydrophobic small molecule drugs. To address this, we developed an affinity hydrogel for DQS by taking advantage of borate-mediated dynamic covalent complexation between DQS and hydroxypropyl guar. The resultant formulation (3% DQS Gel) was characterized by sustained release, low corneal permeation, and extended ocular retention, which were desirable attributes for ocular surface drug delivery. Both in vitro and in vivo studies had been carried out to verify the biocompatibility of 3% DQS Gel. Using corneal fluorescein staining, the Schirmer's test, PAS staining, quantitative PCR and immunohistological analyses as outcome measures, the superior therapeutic effects of 3% DQS Gel over PBS, the hydrogel vehicle and free DQS were demonstrated in a mouse dry eye model. Our DQS delivery strategy reported herein is readily applicable to other hydrophilic small molecule drugs with cis-diol moieties, thus providing a general solution to improve clinical outcomes of numerous diseases.
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Síndromes do Olho Seco , Lágrimas , Animais , Camundongos , Disponibilidade Biológica , Preparações de Ação Retardada/uso terapêutico , Soluções Oftálmicas , Síndromes do Olho Seco/tratamento farmacológico , Polifosfatos/farmacologia , Polifosfatos/uso terapêuticoRESUMO
Iron accumulation causes cell death and disrupts tissue functions, which necessitates chelation therapy to reduce iron overload. However, clinical utilization of deferoxamine (DFO), an iron chelator, has been documented to give rise to systemic adverse effects, including ocular toxicity. This study provided the pathogenic and molecular basis for DFO-related retinopathy and identified retinal pigment epithelium (RPE) as the target tissue in DFO-related retinopathy. Our modeling demonstrated the susceptibility of RPE to DFO compared with the neuroretina. Intriguingly, we established upregulation of hypoxia inducible factor (HIF) 2α and mitochondrial deficit as the most prominent pathogenesis underlying the RPE atrophy. Moreover, suppressing hyperactivity of HIF2α and preserving mitochondrial dysfunction by α-ketoglutarate (AKG) protects the RPE against lesions both in vitro and in vivo. This supported our observation that AKG supplementation alleviates visual impairment in a patient undergoing DFO-chelation therapy. Overall, our study established a significant role of iron deficiency in initiating DFO-related RPE atrophy. Inhibiting HIF2α and rescuing mitochondrial function by AKG protect RPE cells and can potentially ameliorate patients' visual function.
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Quelantes de Ferro , Doenças Retinianas , Humanos , Quelantes de Ferro/efeitos adversos , Morte Celular , Atrofia/induzido quimicamenteRESUMO
Surgery is the primary treatment for recurrent patellar dislocation. However, there is still a lack of consensus regarding the choice of combined surgical methods due to the complexity of the anatomical factors. This study aimed to investigate the efficacy and radiological changes in medial patellofemoral ligament reconstruction (MPFLR) and lateral retinacular release (LRR) with and without tibial tubercle osteotomy (TTO) for recurrent patellar dislocation in patients with a tibial tubercle-trochlear groove (TT-TG) distance of 15 to 20 mm. Fifty-four patients were enrolled in this retrospective study between 2010 and 2014. The average patient age was 21.6 ± 5.0 years. All patients underwent MPFLR and LRR, and in 18 patients, these procedures were combined with TTO. Patients were evaluated preoperatively and postoperatively for patellar lateral shift, patellar tilt angle, TT-TG distance, Q-angle, Caton-Deschamps index (CDI), Kujala, and Lysholm scores. The minimally clinical important difference was used to compare clinical outcomes between two groups. In the mean follow-up of 82.6 ± 15.9 months, functional scores improved significantly in both groups (p < 0.01). There were no significant differences in postoperative function scores between the two groups (Kujala, p = 0.25, mean difference = 1.5, 95% confidence interval [CI]: -1.4-4.4; Lysholm, p = 0.76, mean difference = -0.6, 95% CI: -5.9-4.7). Additionally, TTO significantly decreased Q-angle (23.6 ± 2.4 vs. 17.4 ± 2.9, p < 0.01), TT-TG (17.1 ± 1.5 vs. 10.4 ± 1.8, p < 0.01), and CDI (1.18 ± 0.12 vs. 1.08 ± 0.07, p < 0.01). Combined MPFLR and LRR with and without TTO are both effective techniques for recurrent patellar dislocation. Additional osteotomy can correct patellar alta and tibial tubercle lateralization. However, given that there were no significant differences in postoperative functional scores or recurrence rate between groups, we may not recommend TTO in addition to MPFLR and LRR in patients with TT-TG of 15 to 20 mm. Long-term and prospective cohort studies are required to assess further outcomes.
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Luxações Articulares , Instabilidade Articular , Luxação Patelar , Articulação Patelofemoral , Humanos , Adolescente , Adulto Jovem , Adulto , Luxação Patelar/cirurgia , Articulação Patelofemoral/cirurgia , Estudos Retrospectivos , Estudos Prospectivos , Instabilidade Articular/etiologia , Instabilidade Articular/cirurgia , Recidiva , Tíbia/cirurgia , Osteotomia/métodos , Ligamentos Articulares/cirurgiaRESUMO
Electroretinogram (ERG) captures the electrical responses of photoreceptors, the summation of action potentials from all neurons in the retina elicited by illumination. ERG testing is an incredibly useful tool in obtaining more specific information regarding a retinal dystrophy. Specifically, ERGs are typically used to test photoreceptors and inner retinal function in humans and animals, to diagnose retinal dystrophies, and to monitor disease progression. In this chapter, we will introduce the components of ERGs and the standard ERG protocols for clinical examination. We will also introduce the various specialized ERG tests, which can help to differentiate retinitis pigmentosa (RP) from other retinal disorders. Lastly, we will elaborate on how to use ERGs to predict visual prognosis in RP.
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Retinose Pigmentar , Humanos , Retinose Pigmentar/diagnóstico , Regulador Transcricional ERG , EletrorretinografiaRESUMO
PURPOSE: To evaluate the neurodevelopmental outcomes in premature infants who received intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections to treat retinopathy of prematurity (ROP). DESIGN: Retrospective cohort study. METHODS: This study was conducted using the database from the Taiwan Premature Infant Follow-up Network. Demographic data, systemic risk factors, ROP status, and neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) were collected. Patients were divided into 4 groups: prematurity without ROP, ROP without treatment, ROP with laser treatment, and ROP with intravitreal anti-VEGF treatment. A generalized estimating equation was used for analyzing repeated measurements of Bayley-III at the corrected ages of 6, 12, and 24 months. RESULTS: A total of 2090 patients with a mean gestational age of 31.2 weeks were included. The Bayley-III composite scores of patients with ROP treated with anti-VEGF were comparable to those of patients with ROP without treatment (cognitive: P = .491; language: P = .201; motor: P = .151) and premature patients without ROP (cognitive: P = .985; language: P = .452; motor: P = .169) after adjusting for confounders. Patients with ROP treated with laser photocoagulation exhibited poorer cognitive composite scores than did those without treatment (P < .001), premature patients without ROP (P < .001), and those treated with anti-VEGF (P < .001), but they had similar language and motor composite scores. CONCLUSIONS: Intravitreal anti-VEGF treatment for ROP was not associated with adverse neurodevelopment in premature infants. Further studies are needed to determine whether general anesthesia or sedation used in laser treatment for ROP has significant impacts on neurodevelopmental outcomes.
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Inibidores da Angiogênese , Retinopatia da Prematuridade , Recém-Nascido , Lactente , Humanos , Bevacizumab/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Seguimentos , Retinopatia da Prematuridade/tratamento farmacológico , Estudos Retrospectivos , Taiwan , Recém-Nascido Prematuro , Idade Gestacional , Injeções IntravítreasRESUMO
6-Methoxydihydrosanguinarine (6-MDS) is a natural benzophenanthridine alkaloid extracted from Hylomecon japonica (Thunb.) Prantl. It is the first time to explore the effect and mechanism of 6-MDS in breast cancer. Network pharmacology, molecular docking, and molecular dynamics simulation technology were adopted to identify the potential targets and pathways of 6-MDS in breast cancer. Besides, cell proliferation, apoptosis, and western blotting assays were conducted to investigate the effect of 6-MDS on MCF-7 cells. Network pharmacology, molecular docking, and molecular dynamics simulation results confirmed the effect of 6-MDS on resisting breast cancer via the PI3K/AKT/mTOR signaling pathway. In addition, the functional experiments results demonstrated that 6-MDS inhibited proliferation and induced apoptosis and autophagy. The autophagy inhibitor chloroquine and the silence of Atg5 augmented the effect of 6-MDS on promoting apoptosis. Furthermore, 6-MDS suppressed the PI3K/AKT/mTOR signaling pathway, and the PI3K inhibitor LY294002 enhanced these changes and promoted the 6-MDS pro-apoptotic and autophagy effects. 6-MDS triggered the generation of reactive oxygen species. The pretreatment with antioxidant N-acetyl-L-cysteine reversed the changes induced by 6-MDS, including increases in apoptosis and autophagy and inhibition of the PI3K/AKT/mTOR pathway. In conclusion, 6-MDS induces the apoptosis and autophagy of MCF-7 cells by ROS accumulation to suppress the PI3K/AKT/mTOR signaling pathway.
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Neoplasias da Mama , Proteínas Proto-Oncogênicas c-akt , Humanos , Feminino , Benzofenantridinas/farmacologia , Benzofenantridinas/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células MCF-7 , Neoplasias da Mama/tratamento farmacológico , Simulação de Acoplamento Molecular , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Apoptose , AutofagiaRESUMO
PURPOSE: To analyze the clinical characteristics, surgical outcomes, and risk factors associated with visual outcomes in patients with abusive head trauma (AHT). METHODS: We retrospectively reviewed surgical outcomes of patients with AHT who underwent vitrectomy from 2001 to 2019. The patients' demographics, comprehensive preoperative and postoperative ocular findings, surgical treatments, visual outcomes, and postoperative complications in the medical records were reviewed. Univariable and multivariable analyses were performed to identify the prognostic factors associated with visual outcomes. RESULTS: Fourteen children (18 eyes) diagnosed with AHT who underwent vitrectomy were evaluated. The most common surgical indication was vitreous hemorrhage (n = 6, 33%). Retinal attachment at the final visit was noted in 17 eyes (94%). Thirteen eyes (72%) had a best-corrected visual acuity less than 20/200 after vitrectomy. In the multivariable analysis, optic nerve atrophy (n = 9, 50%) was significantly associated with a poor visual prognosis (final best-corrected visual acuity worse than 20/200) after vitrectomy in children with AHT (95% confidence interval, 1.041-517.963, P = 0.0471). CONCLUSION: The general visual prognosis was poor for patients with AHT needing vitrectomy, although a high rate of retinal attachment was observed. Optic nerve atrophy is a prognostic factor for poor visual outcomes in patients with AHT who received ophthalmic surgery.
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Traumatismos Craniocerebrais , Descolamento Retiniano , Atrofia , Criança , Traumatismos Craniocerebrais/complicações , Traumatismos Craniocerebrais/diagnóstico , Traumatismos Craniocerebrais/cirurgia , Humanos , Prognóstico , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Acuidade VisualRESUMO
Ocular diseases associated with retinal ganglion cell (RGC) degeneration is the most common neurodegenerative disorder that causes irreversible blindness worldwide. It is characterized by visual field defects and progressive optic nerve atrophy. The underlying pathophysiology and mechanisms of RGC degeneration in several ocular diseases remain largely unknown. RGCs are a population of central nervous system neurons, with their soma located in the retina and long axons that extend through the optic nerve to form distal terminals and connections in the brain. Because of this unique cytoarchitecture and highly compartmentalized energy demand, RGCs are highly mitochondrial-dependent for adenosine triphosphate (ATP) production. Recently, oxidative stress and mitochondrial dysfunction have been found to be the principal mechanisms in RGC degeneration as well as in other neurodegenerative disorders. Here, we review the role of oxidative stress in several ocular diseases associated with RGC degenerations, including glaucoma, hereditary optic atrophy, inflammatory optic neuritis, ischemic optic neuropathy, traumatic optic neuropathy, and drug toxicity. We also review experimental approaches using cell and animal models for research on the underlying mechanisms of RGC degeneration. Lastly, we discuss the application of antioxidants as a potential future therapy for the ocular diseases associated with RGC degenerations.
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For a deep understanding of arsenic's mutagenicity, carcinogenicity and teratogenicity, the elucidation of arsenic binding proteins in organisms is a necessary prerequisite. Herein, a biotinylated phenylarsenite (Bio-PAO(III)) probe was synthesized for in situ binding to arsenic binding proteins in HepG2 cells. The Bio-PAO(III)-arsenic binding proteins complexes were captured by the prepared streptavidin-magnetic beads (SA-MBs) by specific interaction of biotin-SA. After magnetic separation, the arsenic binding proteins in the eluent was separated by sodium dodecyl sulfate-polyacrylamide - gel electrophoresis, and the in-gel tryptic digested protein bands were subjected to capillary high performance liquid chromatography coupled with electrospray ionization mass spectrometry analysis. 32 kinds of arsenic binding proteins were identified in HepG2 cells, which could be divided into three groups, structure proteins, enzymes related with tricarboxylic acid cycle and fatty synthesis and transcriptional regulator. Poly [ADP-ribose] polymerase 1 and general transcription factor IIH subunit 1 were identified to bind with arsenicals, which may affect the process of nucleotide excision repair in HepG2 cells.
Assuntos
Arsênio , Arsênio/toxicidade , Proteínas de Transporte , Eletroforese em Gel de Poliacrilamida , Células Hep G2 , Humanos , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
One of the defining features of the retina is the tight metabolic coupling between cells such as photoreceptors and the retinal pigment epithelium (RPE). This necessitates the compartmentalization and proper substrate availability required for specialized processes such as photo-transduction. Glucose metabolism is preferential in many human cell types for adenosine triphosphate generation, yet fatty acid ß-oxidation generates essential fuel for RPE. Here, we provide a brief overview of metabolic demands in both the healthy and dystrophic RPE with an emphasis on fatty acid oxidation. We outline therapies aimed at renormalizing this metabolism and explore future avenues for therapeutic intervention.
RESUMO
An incomplete dislocated intraocular lens (IOL) is often treated with IOL exchange because the IOL subluxates posteriorly during surgery and makes it difficult to fixate the IOL in situ. A trocar blade used for 23-gauge vitrectomy was used to lift and stabilize the IOL-capsular complex. The IOL can then be fixated using a suture loop fixation technique, which was originally limited to patients with decentered IOL. The advantage of this technique is that it allows the remaining zonular fibers and IOL to be preserved. The modified technique using a trocar blade to assist scleral fixation allows the incomplete dislocated IOL to be retrieved and fixated with a simplified surgical procedure.