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Background: Early diagnosis of primary Sjögren's syndrome (pSS) remains difficult due to its insidious onset. Objectives: To identify whether meibomian gland dropout (MGD) is a sensitive and noninvasive predictor of pSS by studying its association with histopathology in labial salivary gland biopsy in patients with clinically suspected pSS. Design: Prospective, randomized, multicenter, comparative effectiveness study. Methods: The study was conducted from July 2022 to July 2023. In all, 56 eligible participants with clinically suspected pSS were recruited from three combined ophthalmology medicine/rheumatology SS clinics. All participants with suspected pSS were evaluated and diagnosed by ophthalmology and rheumatology consultants and underwent infrared imaging of the meibomian glands using Keratograph 5M and histopathological evaluation of labial salivary gland biopsies. The length, width, and tortuosity of the meibomian glands were measured; the dropout rate in the nasal, temporal, and total eyelids was analyzed; and the dropout score was calculated using meibography grading scales. Results: Among the 56 participants, 34 were identified with pSS, and 22 were diagnosed with non-SS dry eye (NSSDE) and served as the control group. We recorded significant differences in the temporal and total MGD rates of the upper eyelids between the pSS and NSSDE groups (all p < 0.01). Improved prediction accuracy was achieved with the temporal and total MGD rates in the upper eyelids, with area under the curve values of 0.94 and 0.91, and optimal cutoff points of 0.78 and 0.75, respectively. Conclusion: MGD in the upper eyelids, especially in the temporal portion, is strongly associated with the histopathological outcome of labial salivary gland biopsy in pSS and is proposed as a highly predictive and noninvasive biomarker for the early diagnosis of pSS. Trial registration: ClinicalTrials.gov identifier: ChiCTR2000038911.
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Background: Mounting evidence suggests a correlation between heavy metals exposure and diabetes. Diabetic retinopathy (DR) is a prevalent and irreversible complication of diabetes that can result in blindness. However, studies focusing on the effects of exposure to heavy metals on DR remain scarce. Thus, this study aimed to investigate the potential correlation between heavy metals exposure and DR. Methods: A total of 1,146 diabetics from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 were included in this study. Heavy metal levels were measured via urine testing. Weighted logistic regression, Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regression, and restricted cubic spline (RCS) were utilized to investigate the potential relationships between exposure to 10 heavy metals and DR. Finally, subgroup analysis was conducted based on the glycemic control status. Results: Among the 1,146 participants, 239 (20.86%) were diagnosed with DR. Those with DR had worse glycemic control and a higher prevalence of chronic kidney disease compared to those without DR. Moreover, both the WQS regression and BKMR models demonstrated a positive relationship between exposure to mixed heavy metals and the risk of DR. The results of weighted logistic regression revealed a positive correlation between cobalt (Co) and antimony (Sb) exposure and the risk of DR (OR = 1.489, 95%CI: 1.064-2.082, p = 0.021; OR = 1.475, 95% CI: 1.084-2.008, p = 0.014), while mercury (Hg) exposure was found to promote DR exclusively in the group with good glycemic control (OR = 1.509, 95% CI: 1.157-1.967, p = 0.003). These findings were corroborated by the results of the RCS analysis. Conclusion: Heavy metal exposure is associated with an increased risk of DR, especially Sb, Co, and Hg exposure. Nevertheless, well-designed prospective studies are warranted to validate these findings.
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Retinopatia Diabética , Metais Pesados , Inquéritos Nutricionais , Humanos , Estudos Transversais , Masculino , Retinopatia Diabética/epidemiologia , Feminino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto , Exposição Ambiental/efeitos adversos , Idoso , Prevalência , Modelos Logísticos , Fatores de RiscoRESUMO
Purpose: Demodex infestation is a risk factor for several ocular surface diseases. However, the prevalence of ocular Demodex infection in the ultra-high altitude population is not clear. This study aimed to compare the prevalence and factors associated with Demodex in populations residing in ultra-high altitude region and sea level areas. Methods: Consecutive patients who visited Shigatse People's Hospital (> 4,000 m) and Shanghai Tongren Hospital (sea level) for eye complaints between January 2023 and January 2024 were included. Subjects were divided into ultra-high altitude and sea level groups. All subjects underwent eyelash epilation for ocular Demodex identification and counting. Demographic and lifestyle information was also collected. Results: A total of 517 subjects were eligible, including 255 subjects in the ultra-high-altitude group and 262 subjects in the sea level group. In the overall analysis, the prevalence of ocular Demodex infection was significantly different between the ultra-high-altitude and sea level groups (15.7% vs. 33.2%, P < 0.001). Multiple logistic regression showed that age, time spent outdoors, and makeup were associated with ocular Demodex infection in both groups. In addition, in the ultra-high-altitude group, people who wear sun hats outdoors were more likely to be infected with Demodex. Conclusion: The infection rate of ocular Demodex in the residents of ultra-high altitude area was significantly lower than that in the residents of sea level area, which may be related to lower ambient temperature, lower humidity, and higher solar radiation. Additionally, age, time spent outdoors, and makeup may be associated with ocular Demodex infection.
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Paraconiothyrium cyclothyrioides is a coelomycetous fungus species that was recently identified. We present a case of an elderly farmer with chronic skin lesions of the opisthenar caused by P. cyclothyrioides.
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OBJECTIVE: This study investigated the impact of Aspergillus niger lysing polysaccharide monooxygenase (AnLPMO) on in vitro rumen microbial fermentation of rice straw. METHODS: AnLPMO was heterologously expressed in Escherichia coli. Fourier transform infrared spectrometry and X-ray photoelectron spectroscopy analyzed the surface structure of rice straw after AnLPMO treatment. Two in vitro experiments, coupled with 16S highthroughput sequencing and quantitative real-time polymerase chain reaction techniques, assessed the influence of AnLPMO on rumen microbial fermentation of rice straw. RESULTS: AnLPMO exhibited peak activity at 40°C and pH 6.5, with a preference for rice straw xylan hydrolysis, followed by Avicel. AnLPMO application led to the fractional removal of cellulose and hemicelluloses and a notable reduction in the levels of carbon elements and C-C groups present on the surface of rice straw. Compared to the control (no AnLPMO), supplementing AnLPMO at 1.1 to 2.0 U significantly enhanced in vitro digestibility of dry matter (IVDMD, p<0.01), total gas production (p<0.01), and concentrations of total volatile fatty acids (VFA, p<0.01), acetate (p<0.01), and ammonia-N (p<0.01). Particularly, the 1.4 U AnLPMO group showed a 14.8% increase in IVDMD. In the second experiment, compared to deactivated AnLPMO (1.4 U), supplementing bioactive AnLPMO at 1.4 U increased IVDMD (p = 0.01), total gas production (p = 0.04), and concentrations of total VFA (p<0.01), propionate (p<0.01), and ammonia-N (p<0.01), with a limited 9.6% increase in IVDMD. Supplementing AnLPMO stimulated the growth of ruminal bacterial taxa facilitating fiber degradation, including Proteobacteria, Spirochaetes, Succinivibrio, Rikenellaceae_RC9_ Gut_Group, Prevotelaceae_UCG-003, Desulfovibrio, Fibrobacter succinogenes, Ruminococcus albus, R. flavefaciens, Prevotella bryantii, P. ruminicola, and Treponema bryantii. CONCLUSION: These findings highlight AnLPMO's potential as a feed additive for improving rice straw utilization in ruminant production.
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Objective: To elucidate the role of the competitive endogenous RNA (ceRNA) network in immune infiltration of diabetic retinopathy (DR). Methods: We obtained differentially expressed (DE) circRNAs, miRNAs and mRNAs from the Gene Expression Omnibus database. Then, we identified immune infiltration by CIBERSORT and single-sample gene set enrichment analysis and discovered co-expression genes by weighted gene co-expression network analysis. Furthermore, STAT1-mediated Th1 differentiation was determined in DR cell models, DR patients and DR mouse models. Results: hsa_circ_0087100/hsa-miR-6743-5p/STAT1 was involved in immune infiltration of Th1 cells. Aberrant expression of the ceRNA network and STAT1-mediated Th1 differentiation was thus verified in vitro and in vivo. Conclusion: hsa_circ_0087100/hsa-miR-6743-5p/STAT1 may affect Th1 cell differentiation in DR.
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Retinopatia Diabética , RNA Circular , Células Th1 , Animais , Humanos , Camundongos , Diferenciação Celular , Bases de Dados Factuais , Diabetes Mellitus , Retinopatia Diabética/genética , MicroRNAs/genética , RNA Endógeno Competitivo , Fator de Transcrição STAT1/genética , RNA Circular/metabolismoRESUMO
BACKGROUND: Studies have shown that tet methylcytosine dioxygenase 2 (TET2) is highly expressed in diabetic retinopathy (DR), which reduces the DNA methylation of downstream gene promoters and activates the transcription. Abnormally expressed TET2 and downstream genes in a high-glucose environment are associated with retinal capillary leakage and neovascularization. Here, we investigated the downstream genes of TET2 and its potential association with neovascularization in proliferative diabetic retinopathy (PDR). METHODS: GSE60436, GSE57362, and GSE158333 datasets were analyzed to identify TET2-related hypomethylated and upregulated genes in PDR. Gene expression and promoter methylation of these genes under high glucose treatment were verified. Moreover, TET2 knockdown was used to assess its impact on tube formation and migration in human retinal microvascular endothelial cells (HRMECs), as well as its influence on downstream genes. RESULTS: Our analysis identified three key genes (PARVB, PTPRE, ECM1) that were closely associated with TET2 regulation. High glucose-treated HRMECs exhibited increased expression of TET2 and ECM1 while decreasing the promoter methylation level of ECM1. Subsequently, TET2 knockdown led to decreased migration ability and tube formation function of HRMECs. We further found a decreased expression of PARVB, PTPRE, and ECM1, accompanied by an increase in the promoter methylation of ECM1. CONCLUSIONS: Our findings indicate the involvement of dysregulated TET2 expression in neovascularization by regulating the promoter methylation and transcription of downstream genes (notably ECM1), eventually leading to PDR. The TET2-induced hypomethylation of downstream gene promoters represents a potential therapeutic target and offers a novel perspective on the mechanism underlying neovascularization in PDR.
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Diabetes Mellitus , Retinopatia Diabética , Dioxigenases , Humanos , Retinopatia Diabética/genética , Metilação de DNA , Células Endoteliais/metabolismo , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Glucose/farmacologia , Glucose/metabolismo , Diabetes Mellitus/genética , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dioxigenases/genética , Dioxigenases/metabolismoRESUMO
BACKGROUND/AIMS: This study evaluates the performance of the Airdoc retinal artificial intelligence system (ARAS) for detecting multiple fundus diseases in real-world scenarios in primary healthcare settings and investigates the fundus disease spectrum based on ARAS. METHODS: This real-world, multicentre, cross-sectional study was conducted in Shanghai and Xinjiang, China. Six primary healthcare settings were included in this study. Colour fundus photographs were taken and graded by ARAS and retinal specialists. The performance of ARAS is described by its accuracy, sensitivity, specificity and positive and negative predictive values. The spectrum of fundus diseases in primary healthcare settings has also been investigated. RESULTS: A total of 4795 participants were included. The median age was 57.0 (IQR 39.0-66.0) years, and 3175 (66.2%) participants were female. The accuracy, speciï¬city and negative predictive value of ARAS for detecting normal fundus and 14 retinal abnormalities were high, whereas the sensitivity and positive predictive value varied in detecting different abnormalities. The proportion of retinal drusen, pathological myopia and glaucomatous optic neuropathy was significantly higher in Shanghai than in Xinjiang. Moreover, the percentages of referable diabetic retinopathy, retinal vein occlusion and macular oedema in middle-aged and elderly people in Xinjiang were significantly higher than in Shanghai. CONCLUSION: This study demonstrated the dependability of ARAS for detecting multiple retinal diseases in primary healthcare settings. Implementing the AI-assisted fundus disease screening system in primary healthcare settings might be beneficial in reducing regional disparities in medical resources. However, the ARAS algorithm must be improved to achieve better performance. TRIAL REGISTRATION NUMBER: NCT04592068.
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Retinopatia Diabética , Drusas Retinianas , Pessoa de Meia-Idade , Idoso , Humanos , Feminino , Masculino , Inteligência Artificial , Estudos Transversais , Sensibilidade e Especificidade , China/epidemiologia , Retinopatia Diabética/diagnóstico , Atenção Primária à Saúde , Programas de RastreamentoRESUMO
PURPOSE: To investigate the effectiveness of two regimens of ranibizumab-assisted pars plana vitrectomy in the treatment of patients with proliferative diabetic retinopathy. METHODS: This is a prospective, 6-month, randomized controlled trial. Eighty patients with 87 eyes requiring pars plana vitrectomy treatment for proliferative diabetic retinopathy were included and randomly divided into a 1.0-mg injection group and a 0.5-mg injection group. The ranibizumab was delivered intraoperatively, at the close of surgery. The vitreous hemorrhage grade, best-corrected visual acuity, central macular thickness, and safety data were assessed to Month 6. RESULTS: The 1.0-mg injection group had a milder grade and a lower reoccurrence rate of early postoperatively vitreous hemorrhage than the 0.5-mg injection group (35.0% and 63.4%, respectively, P = 0.0195). The mean best-corrected visual acuity of two groups was significantly improved from baseline to 6 months after surgery, 1.60 ± 0.72 Logarithm of the Minimum Angle of Resolution (LogMAR) (<20/200) to 0.47 ± 0.49 LogMAR (20/59) for the 1.0-mg injection group and 1.51 ± 0.69 LogMAR (<20/200) to 0.50 ± 0.31 LogMAR (20/63) for the 0.5-mg injection group, but there was no significant difference between the two groups ( P = 0.74). There was no significant difference in the mean decrease in central macular thickness and probability of postoperative adverse events between the two groups. CONCLUSION: Intravitreal injection of 1.0 mg of ranibizumab after pars plana vitrectomy compared with the recommended dose of 0.5 mg significantly reduced the recurrence and severity of early postoperative vitreous hemorrhage in patients with proliferative diabetic retinopathy. It also contributed to the early recovery of visual acuity after surgery and did not increase postoperative adverse events.
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Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/tratamento farmacológico , Injeções Intravítreas , Estudos Prospectivos , Ranibizumab/efeitos adversos , Ranibizumab/uso terapêutico , Resultado do Tratamento , Vitrectomia/efeitos adversos , Hemorragia Vítrea/cirurgiaRESUMO
PURPOSE: This study aimed to explore the influence of high altitude on myopia, macular choroidal thickness (mCT), and macular retinal thickness (mRT) in adolescents. METHODS: Two schools, one in Shanghai (at sea level) and one in Shigatse, Tibet (more than 4000 m above sea level), were selected. Refractive error was measured by an autorefractor instrument and subjective refraction, and mCT and mRT were measured at three concentric circles by optical coherence tomography. Student's t -test, Chi-square test, and multiple linear regression analyses were used to analyze the data. RESULTS: A total of 1114 participants (657 and 457 in Shanghai and Tibet, respectively) were enrolled in this cross-sectional study. The average age of the participants was 18.81 ± 1.10 years, and 44.34% were males. The spherical equivalent (SE) of adolescents in Shanghai was significantly lower than that of adolescents in Tibet (-4.14 ± 2.37 D and -2.12 ± 1.87 D, P < 0.01). The prevalence of myopia and high myopia among adolescents in Shanghai (94.52%, 19.48%) was significantly higher than those among adolescents in Tibet (44.74%, 2.41%) ( P < 0.01). The mCT of Tibetan adolescents was significantly thicker than that of Shanghai adolescents (295.80 ± 62.46 µm and 218.71 ± 61.42 µm, P < 0.01), especially the central mCT. The mRT of Tibetan adolescents was also thicker than that of Shanghai adolescents (301.42 ± 23.26 µm and 281.04 ± 12.24 µm, P < 0.01). CONCLUSIONS: Compared with Shanghai adolescents, the choroid of Tibet adolescents is thicker, and the myopia prevalence is lower. It is speculated that increased altitude is associated with the thickening of mCT and a low myopia prevalence.
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Altitude , Miopia , Masculino , Humanos , Adolescente , Adulto Jovem , Adulto , Feminino , Tibet/epidemiologia , Estudos Transversais , China , Miopia/diagnóstico , Miopia/epidemiologia , Corioide , Tomografia de Coerência Óptica/métodosRESUMO
Background: The relationship between the optical flow ratio (OFR) and clinical outcomes in patients with coronary artery disease (CAD) after percutaneous coronary stent implantation (PCI) remains unknown. Objective: To examine the correlation between post-PCI OFR and clinical outcomes in patients with CAD following PCI. Methods: Patients who underwent optical coherence tomography (OCT) guided PCI at Guangdong Provincial People's Hospital were retrospectively and continuously enrolled. Clinical data, post-PCI OCT characteristics, and OFR measurements were collected and analyzed to identify predictors of target vessel failure (TVF) after PCI. Results: Among 354 enrolled patients, 26 suffered TVF during a median follow-up of 484 (IQR: 400-774) days. Post-PCI OFR was significantly lower in the TVF group than in the non-TVF group (0.89 vs. 0.93; P = 0.001). In multivariable Cox regression analysis, post-PCI OFR (HR per 0.1 increase: 0.60; 95% CI: 0.41-0.89; P = 0.011), large stent edge dissection (HR: 3.85; 95% CI: 1.51-9.84; P = 0.005) and thin-cap fibroatheroma (TCFA) (HR: 2.95; 95% CI: 1.19-7.35; P = 0.020) in the non-stented segment were independently associated with TVF. In addition, the inclusion of post-PCI OFR to baseline characteristics and post-PCI OCT findings improved the predictive power of the model to distinguish subsequent TVF after PCI (0.838 vs. 0.796; P = 0.028). Conclusion: The post-PCI OFR serves as an independent determinant of risk for TVF in individuals with CAD after PCI. The inclusion of post-PCI OFR assessments, alongside baseline characteristics and post-PCI OCT findings, substantially enhances the capacity to differentiate the subsequent manifestation of TVF in CAD patients following PCI.
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BACKGROUND: Minimizing mortality losses due to multiple stress and obtaining maximum performance are the production goals for newly received cattle. In recent years, vaccination and metaphylaxis treatment significantly decreased the mortality rate of newly received cattle, while the growth block induced by treatment is still obvious. Assessment of blood metabolites and behavior monitoring offer potential for early identification of morbid animals. Moreover, the ruminal microorganisms' homeostasis is a guarantee of beef steers' growth and health. The most critical period for newly received cattle is the first-month post-transport. Therefore, analyzing rumen metagenomics, rumen metabolomics, host metabolomics, and their interaction during receiving period (1 day before transport and at days 1/4, 16, and 30 after transport) is key to revealing the mechanism of growth retardation, and then to formulating management and nutritional practices for newly received cattle. RESULTS: The levels of serum hormones (COR and ACTH), and pro-inflammatory factors (IL-1ß, TNF-α, and IL-6) were highest at day 16, and lowest at day 30 after arrival. Meanwhile, the antioxidant capacity (SOD, GSH-Px, and T-AOC) was significantly decreased at day 16 and increased at day 30 after arrival. Metagenomics analysis revealed that rumen microbes, bacteria, archaea, and eukaryota had different trends among the four different time points. At day 16 post-transport, cattle had a higher abundance of ruminal bacteria and archaea than those before transport, but the eukaryote abundance was highest at day 30 post-transport. Before transport, most bacteria were mainly involved in polysaccharides digestion. At day 4 post-transport, the most significantly enriched KEGG pathways were nucleotide metabolism (pyrimidine metabolism and purine metabolism). At day 16 post-transport, the energy metabolism (glycolysis/gluconeogenesis, pyruvate metabolism) and ruminal contents of MCP and VFAs were significantly increased, but at the same time, energy loss induced by methane yields (Methanobrevibacter) together with pathogenic bacteria (Saccharopolyspora rectivirgula) were also significantly increased. At this time, the most upregulated ruminal L-ornithine produces more catabolite polyamines, which cause oxidative stress to rumen microbes and their host; the most downregulated ruminal 2',3'-cAMP provided favorable growth conditions for pathogenic bacteria, and the downregulated ruminal vitamin B6 metabolism and serum PC/LysoPC disrupt immune function and inflammation reaction. At day 30 post-transport, the ruminal L-ornithine and its catabolites (mainly spermidine and 1,3-propanediamine) were decreased, and the serum PC/LysoPC and 2',3'-cNMPs pools were increased. This is also consistent with the changes in redox, inflammation, and immune status of the host. CONCLUSIONS: This study provides new ideas for regulating the health and performance of newly received cattle during the receiving period. The key point is to manage the newly received cattle about day 16 post-transport, specifically to inhibit the production of methane and polyamines, and the reproduction of harmful bacteria in the rumen, therefore improving the immunity and performance of newly received cattle. Video Abstract.
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Dieta , Microbiota , Bovinos , Animais , Dieta/veterinária , Rúmen/microbiologia , Bactérias/genética , Bactérias/metabolismo , Archaea/metabolismo , Inflamação/metabolismo , Metano/metabolismo , Ornitina/metabolismo , Poliaminas/metabolismo , Ração Animal/análise , FermentaçãoRESUMO
Diabetic retinopathy (DR) is currently recognized as the leading cause of end-stage eye disease. Pipecolic acid, a metabolite, has a significant regulatory effect on several pathological processes. However, the exact mechanism by which it causes damage in diabetic retinopathy is unknown. Between September 2021 and December 2022, 40 patients were retrospectively examined and divided into two groups: the healthy group (n = 20) and the DR group (n = 20). Metabolomic analysis found that pipecolic acid plays an important role in this process. Streptozotocin-induced diabetic mice and high-glucose cultured human retinal capillary endothelial cells (HRCECs) were then treated with pipecolic acid. Several oxidative stress measurements and RNA sequencing of retinal cells were tested. A gene interaction study was conducted using bioinformatics. Comparison of serological metabolites between healthy volunteers and DR patients showed that pipecolic acid was significantly lower in DR patients, and there was a negative correlation between the level of pipecolic acid with blood glucose and glycated hemoglobin. Yes-associated protein (YAP) mRNA, Malondialdehyde (MDA), and reactive oxygen species (ROS) levels were significantly higher in diabetic mice, but glutathione peroxidase (GSH-Px) levels were significantly lower. Pipecolic acid significantly alleviated oxidative stress and YAP expression. The number of vascular tubes was significantly higher in the DR group, and pipecolic acid treatment significantly reduced tube formation. RNA-Sequencing analysis revealed that YAP and glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4) expression was reduced, and functional enrichment analysis revealed that ferroptosis and Hippo signaling pathways play an important role in this process. Additionally, pipecolic acid's ability to improve DR is diminished after YAP and GPX4 ablation. This study found that pipecolic acid, as a metabolite, may impede the progression of DR by inhibiting the YAP-GPX4 signaling pathway.
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Diabetes Mellitus Experimental , Retinopatia Diabética , Ferroptose , Humanos , Camundongos , Animais , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Retinopatia Diabética/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Células Endoteliais/metabolismo , Estudos Retrospectivos , Espécies Reativas de Oxigênio/metabolismo , Transdução de SinaisRESUMO
Endothelial dysfunction is a critical and initiating factor of the vascular complications of diabetes. Inflammation plays an important role in endothelial dysfunction regulated by epigenetic modifications. N6-methyladenosine (m6A) is one of the most prevalent epigenetic modifications in eukaryotic cells. In this research, we identified an m6A demethylase, fat mass and obesity-associated protein (FTO), as an essential epitranscriptomic regulator in diabetes-induced vascular endothelial dysfunction. We showed that enhanced FTO reduced the global level of m6A in hyperglycemia. FTO knockdown in endothelial cells (ECs) resulted in less inflammation and compromised ability of migration and tube formation. Compared with EC Ftofl/fl diabetic mice, EC-specific Fto-deficient (EC FtoΔ/Δ) diabetic mice displayed less retinal vascular leakage and acellular capillary formation. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) combined with RNA-Seq indicated that Tnip1 served as a downstream target of FTO. Luciferase activity assays and RNA pull-down demonstrated that FTO repressed TNIP1 mRNA expression by erasing its m6A methylation. In addition, TNIP1 depletion activated NF-κB and other inflammatory factors, which aggravated retinal vascular leakage and acellular capillary formation, while sustained expression of Tnip1 by intravitreal injection of adeno-associated virus alleviated endothelial impairments. These findings suggest that the FTO-TNIP1-NF-κB network provides potential targets to treat diabetic vascular complications.
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Diabetes Mellitus Experimental , Doenças Vasculares , Animais , Camundongos , Metilação , Diabetes Mellitus Experimental/genética , NF-kappa B/genética , NF-kappa B/metabolismo , Células Endoteliais/metabolismo , RNA/genética , Inflamação/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismoRESUMO
PURPOSE: The aim of this study was to assess the efficacy and safety of a novel releasing-closing-tapping approach in the treatment of persistent macular holes (PMHs) after initial surgery with internal limiting membrane (ILM) peeling. METHODS: We retrospectively analyzed patients with PMHs after initial surgery with ILM peeling who were treated with a novel releasing-closing-tapping approach. After repeated pars plana vitrectomy (PPV), the surgeon effectively released the adhesion between the edges and retinal pigment epithelium (RPE) by gently scraping the retinal neuroepithelium. Then, the hole was converted into a transverse slit, and the edges were gently tapped flat so that they attached to the RPE, and no space was left under the edges. Finally, air tamponade was carried out. The primary outcome measures included MH closure and the change in best-corrected visual acuity (BCVA) from preoperatively to postoperatively. RESULTS: The study included 11 PMH patients with a mean age of 63.82 ± 3.31 years. The mean minimum linear diameter of PMHs was 666.3 ± 208.1 µm, and the mean basal diameter was 1547.2 ± 351.8 µm. MH closure was achieved in 90.9% (10/11) of eyes, with significant improvement of visual acuity from 1.19 ± 0.30 logMAR to 0.65 ± 0.29 logMAR postoperatively. CONCLUSION: The releasing-closing-tapping approach with repeated PPV is a simple, effective, and safe surgical procedure for refractory PMHs after initial surgery with ILM peeling that can significantly improve the visual outcome and achieve a high surgical success rate.
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Membrana Epirretiniana , Perfurações Retinianas , Humanos , Pessoa de Meia-Idade , Idoso , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/cirurgia , Membrana Epirretiniana/cirurgia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Vitrectomia/métodos , Membrana Basal/cirurgia , Cadáver , Resultado do TratamentoRESUMO
Diabetic macular edema (DME) is a common complication of diabetic retinopathy and is the leading cause of vision loss in diabetic patients. Various factors, such as metabolic disorders and inflammation caused by hyperglycemia, are involved in the occurrence and development of DME, but the specific mechanism is still unclear. Müller cells are a type of macroglial cell unique to the fundus, distributed throughout the retina, and they play a unique role in retinal homeostasis. This article reviews the role of Müller cells in the pathological process of DME and the research progress in the treatment of DME by targeting Müller cells through gene therapy.
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Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Retinopatia Diabética/patologia , Edema Macular/etiologia , Edema Macular/patologia , Células Ependimogliais/patologia , Retina/patologia , Fundo de Olho , Diabetes Mellitus/patologiaRESUMO
BACKGROUND: To report a case in which silicone oil accidentally entered Berger's space (BS) after vitrectomy and to explore the effective treatments and possible etiological mechanisms. CASE PRESENTATION: A 68-year-old male underwent vitrectomy and silicone oil injection for the treatment of retinal detachment (RD) in the right eye. Six months later, we noticed an unexpected lens-like round translucent substance located behind the posterior lens capsule and diagnosed it as BS filled by silicone oil. Subsequently, we conducted vitrectomy and the drainage of the silicone oil in BS in the second surgery. A 3-month follow-up showed significant anatomic recovery and visual recovery. CONCLUSIONS: Our case report presents a patient with silicone oil entering BS after vitrectomy and provides photographs of BS from a relatively unique perspective. Furthermore, we illustrate the surgical treatment procedure and reveal the possible etiology and prevention method of silicon oil entering BS, which will provide good insights for clinical diagnosis and treatment.
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Cristalino , Óleos de Silicone , Masculino , Humanos , Idoso , Óleos de Silicone/efeitos adversos , Silicones , Drenagem , OlhoRESUMO
This study aimed to explore the substance basis and mechanisms of Shen-qi-wang-mo Granule (SQWMG), a traditional Chinese medicine prescription that had been clinically utilized to treat retinal vein occlusion (RVO) for 38 years. Components in SQWMG were analyzed by UPLC-Triple-TOF/MS and a total of 63 components were identified with ganoderic acids (GA) being the largest proportion. Potential targets of active components were retrieved from SwissTargetPrediction. RVO-related targets were acquired from related disease databases. Core targets of SQWMG against RVO were acquired by overlapping the above targets. The 66 components (including 5 isomers) and 169 targets were obtained and concluded into a component-target network. Together with biological enrichment analysis of targets, it revealed the crucial role of the "PI3K-Akt signaling pathway", "MAPK signaling pathway" and their downstream factor iNOS and TNF-α. The 20 key targets of SQWMG in treating RVO were acquired from the network and pathway analysis. The effects of SQWMG on targets and pathways were validated by molecular docking based on AutoDock Vina and qPCR experiment. The molecular docking showed great affinity for these components and targets, especially on ganoderic acids (GA) and alisols (AS), which were both triterpenoids and qPCR exhibited remarkably reduced inflammatory factor gene expression through regulation of these two pathways. Finally, the key components were also identified from rat serum after treatment of SQWMG.
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Medicamentos de Ervas Chinesas , Oclusão da Veia Retiniana , Animais , Ratos , Farmacologia em Rede , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Oclusão da Veia Retiniana/tratamento farmacológico , Espectrometria de Massas em Tandem , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêuticoRESUMO
BACKGROUND: To investigate the prevalence and predictors of retinal breaks reopening after vitrectomy with air tamponade in rhegmatogenous retinal detachment (RRD). METHODS: A retrospective cohort study was conducted in Shanghai General Hospital. Chart review was performed among 1715 patients with primary RRD who received pars plana vitrectomy (PPV) with air tamponade as initial management. Patients were followed up for recurrence. The clinical features of the eyes with retinal breaks reopening were recorded. Logistic regression was constructed to investigate the predictors for breaks reopening. RESULTS: A total of 137 (7.99%) patients had recurrent retinal detachment after PPV with air tamponade. The causes of surgery failure included new or missed retinal breaks (48.9%), reopening of original tears (43.8%) and proliferative vitreoretinopathy (7.3%). The median time to recurrence for the patients with breaks reopening was 18.0 days. Multivariate logistic regression indicated that the presence of retinal break(s) ≥ 1.5 disc diameters (DD) (odds ratio [OR]: 2.68, 95% confidence interval [CI]: 11.04-6.92, P = 0.041), and shorter period for restricted activities (OR: 0.94, 95% CI: 0.89-0.99, P = 0.020) were the independent predictors for breaks reopening. CONCLUSIONS: Breaks reopening is an important cause for retinal redetachment after PPV with air tamponade in primary RRD. The first 2-4 weeks after surgery is the "risk period" for breaks reopening. Special attention should be paid for patients with retinal break(s) ≥ 1.5 DD. A prolonged period for restricted activities is recommended.
RESUMO
This study was conducted to explore the rumen fermentation characteristics, bacterial diversity, and community composition of Hu sheep under four energy provision strategies. Ninety-six Hu sheep (body weight: 17.78 ± 1.24 kg) were equally assigned to four energy provision strategies: (1) low-energy diet for the whole finishing stage (LL); (2) high-energy diet for the whole finishing stage (HH); (3) low-energy diet in the early finishing stage and high-energy diet in the late finishing stage (LH); (4) high-energy diet in the early finishing stage and low-energy diet in the late finishing stage (HL). The results showed that the proportion of acetate was lower in the HH group than that in the HL group, whereas the opposite result was observed for the butyrate proportion (p < 0.05). The Chao 1, observed species, PD whole tree, and Shannon index of the rumen bacteria were higher in the LL group than that in the HH group (p < 0.05). The taxonomic annotations revealed that the Patescibacteria, Rikenellaceae RC9 gut group, Christensenellaceae R-7 group, and Anaeroplasma abundances were higher in the HL group than that in the HH group, and the opposite results were observed regarding the relative abundances of Selenomonas and Anaerovibrio (p < 0.05). The relative abundances of Spirochaetota and Treponema were higher in the LH group than that in the HH group (p < 0.05). Moreover, the analysis of similarity (ANOSIM) showed significant differences between groups (R = 0.6792 and p = 0.001). This study indicates that the energy provision strategy had little impact on the rumen fermentation characteristics, while it heavily affected the rumen bacterial diversity and community composition. This study may provide insight into the rumen fermentation characteristics and bacterial community under routine finishing models and contribute to the optimization of energy provision strategies of Hu sheep.