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Increased cellular senescence burden contributes in part to age-related organ dysfunction and pathologies. In our study, using mouse models of natural aging, we observed structural and functional decline in the aged retina, which was accompanied by the accumulation of senescent cells and senescence-associated secretory phenotype factors. We further validated the senolytic and senomorphic properties of procyanidin C1 (PCC1) both in vitro and in vivo, the long-term treatment of which ameliorated age-related retinal impairment. Through high-throughput single-cell RNA sequencing (scRNA-seq), we comprehensively characterized the retinal landscape after PCC1 administration and deciphered the molecular basis underlying the senescence burden increment and elimination. By exploring the scRNA-seq database of age-related retinal disorders, we revealed the role of cellular senescence and the therapeutic potential of PCC1 in these pathologies. Overall, these results indicate the therapeutic effects of PCC1 on the aged retina and its potential use for treating age-related retinal disorders.
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Envejecimiento , Catequina , Senescencia Celular , Proantocianidinas , Retina , Animales , Retina/metabolismo , Retina/efectos de los fármacos , Ratones , Proantocianidinas/farmacología , Proantocianidinas/metabolismo , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Senescencia Celular/efectos de los fármacos , Catequina/farmacología , Catequina/metabolismo , Catequina/química , Biflavonoides/farmacología , Senoterapéuticos/farmacología , Ratones Endogámicos C57BL , Humanos , Enfermedades de la Retina/tratamiento farmacológico , Enfermedades de la Retina/metabolismo , Enfermedades de la Retina/patologíaRESUMEN
Glaucoma is the leading cause of irreversible blindness worldwide. Previous observational studies have suggested a relationship between central corneal thickness (CCT) and glaucoma; however, the results are inconsistent. This study aimed to investigate whether CCT is associated with a risk for developing open-angle glaucoma (OAG). We employed two-sample Mendelian randomization to assess the relationship between CCT and OAG, namely, primary open-angle glaucoma (POAG) and suspected glaucoma. Genetic instruments composed of variants associated with CCT at genome-wide significance (P < 5 × 10-8) were obtained from published genome-wide association studies from Iglesias et al. for discovery and Bonnemaijer et al. for replication. Summary-level statistics for these instruments for the OAG were obtained from the FinnGen Project (Release 10). Inverse-variance-weighted regression of genetic susceptibility predicted that increased CCT was positively associated with an increased risk for POAG (odds ratio [OR], 1.005; 95% confidence interval [CI], 1.002-1.008; P = 0.001) and suspected glaucoma (OR, 1.006; 95% CI, 1.003-1.009; P < 0.001). In the replication sample of CCT, increased CCT was also positively associated with an increased risk for POAG (OR, 1.004; 95% CI, 1.000-1.008; P = 0.029) and suspected glaucoma (OR, 1.005; 95% CI, 1.001-1.008; P = 0.013). We found genetic evidence supporting a potential causal association between increased CCT and the risk of POAG and suspected glaucoma in the European population. This findings indicates the clinical significance of CCT in the diagnosis and treatment of glaucoma. Further studies are needed to elucidate the underlying mechanisms of this causal relationship.
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Córnea , Estudio de Asociación del Genoma Completo , Glaucoma de Ángulo Abierto , Análisis de la Aleatorización Mendeliana , Glaucoma de Ángulo Abierto/genética , Humanos , Córnea/patología , Polimorfismo de Nucleótido Simple , Presión Intraocular/fisiología , Factores de Riesgo , Predisposición Genética a la Enfermedad , Paquimetría Corneal , Masculino , FemeninoRESUMEN
Retinopathy of prematurity (ROP) continues to pose a significant threat to the vision of numerous children worldwide, primarily owing to the increased survival rates of premature infants. The pathologies of ROP are mainly linked to impaired vascularization as a result of hyperoxia, leading to subsequent neovascularization. Existing treatments, including anti-vascular endothelial growth factor (VEGF) therapies, have thus far been limited to addressing pathological angiogenesis at advanced ROP stages, inevitably leading to adverse side effects. Intervention to promote physiological angiogenesis during the initial stages could hold the potential to prevent ROP. Adenosine A2A receptors (A2AR) have been identified in various ocular cell types, exhibiting distinct densities and functionally intricate connections with oxygen metabolism. In this review, we discuss experimental evidence that strongly underscores the pivotal role of A2AR in ROP. In particular, A2AR blockade may represent an effective treatment strategy, mitigating retinal vascular loss by reversing hyperoxia-mediated cellular proliferation inhibition and curtailing hypoxia-mediated neovascularization in oxygen-induced retinopathy (OIR). These effects stem from the interplay of endothelium, neuronal and glial cells, and novel molecular pathways (notably promoting TGF-ß signaling) at the hyperoxia phase. We propose that pharmacological targeting of A2AR signaling may confer an early intervention for ROP with distinct therapeutic benefits and mechanisms than the anti-VEGF therapy.
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Retinopathy of prematurity (ROP) is an important cause of avoidable childhood visual impairment, and the increase in number and survival of premature infants may inflate its burden globally. We aimed to comprehensively assess the trends and inequalities in the burden of ROP-related visual impairment and to identify improvement gaps to facilitate appropriate actions in neonatal care systems. We obtained ROP data from the Global Burden of Disease 2019 study. We employed joinpoint regression analysis to assess the trends of the burden of ROP-related visual impairment, measured by age-standardised prevalence rates, health equity analysis methods to evaluate cross-country burden inequalities, and data envelopment and stochastic frontier analyses to identify improvement gaps based on the development status, i.e., sociodemographic index (SDI). Between 1990 and 2019, the age-standardised prevalence rates of ROP-related visual impairment significantly increased worldwide (average annual percentage change: 0.23 [95% confidence interval, 0.21-0.26] among males and 0.26 [0.25-0.27] among females), primarily in developed regions. Although significant SDI-related cross-country inequalities were identified, these reduced over time (slope index of inequality: -57.74 [-66.22 to -49.25] in 1990 to -29.68 [-38.39 to -20.97] in 2019; health concentration index: -0.11 [-0.13 to -0.09] in 1990 to -0.07 [-0.09 to -0.06] in 2019). Notably, some less-developed countries exhibited superior performance despite limited resources, whereas others with a higher SDI delivered lagging performance. Conclusion: The global burden of ROP-related visual impairment has steadily increased between 1990 and 2019, with disproportionate burden concentration among less-developed countries, requiring appropriate preventive and intervention measures. What is Known: ⢠Retinopathy of prematurity (ROP) is an important cause of avoidable childhood visual impairment. ⢠The prevalence of ROP is anticipated to increase due to the growing number of extremely premature infants. What is New: ⢠The prevalence of ROP-related visual impairment has increased worldwide, primarily in developed regions, with declining but persisting cross-country inequalities. ⢠The increasing burden of ROP-related visual impairment should be considered as part of global and national health agendas, requiring interventions with proven efficacy.
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Enfermedades del Recién Nacido , Retinopatía de la Prematuridad , Recién Nacido , Masculino , Lactante , Femenino , Humanos , Niño , Retinopatía de la Prematuridad/complicaciones , Retinopatía de la Prematuridad/epidemiología , Países en Desarrollo , Recien Nacido Extremadamente Prematuro , Prevalencia , Trastornos de la Visión/epidemiología , Trastornos de la Visión/etiología , Edad GestacionalRESUMEN
BACKGROUND: The presence of sensory impairment among older age cohorts exerts a significant impact on both individuals and society generally. Although the impact of dietary patterns on health is vital across all stages of life, there still a paucity of comprehensive research on the association between dietary variety and sensory impairments. OBJECTIVE: To investigate the potential relationship between dietary diversity and the prevalence of visual and hearing impairment or dual sensory impairments (visual and hearing impairment) among the oldest old population. METHODS: This is a cross-sectional study relied on data obtained from the 2018 survey conducted by the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Subjects aged 80 and older with complete vision and hearing data were included in the study. Multivariate logistic regression models were developed to examine the association between dietary components and visual and hearing impairment while controlling for age, gender, socioeconomic demographic factors, living habits, other food habits, and general health status. RESULTS: The study included 10,093 participants, with an average age of 92.29 ± 7.75 years. Vision and hearing function were assessed based on the ability to distinguish the direction of the break in the circle and the requirement for hearing aids, respectively. Upon controlling for confounding variables, individuals with a greater Dietary Diversity Score (DDS, the number of food groups, range: 1-11) had a reduced likelihood of experiencing visual impairment (odds ratio [OR] = 0.944, 95% confidence interval [CI], 0.915-0.974) and dual sensory impairment (OR = 0.930, 95% CI, 0.905-0.955). In comparison to the low dietary variety group (insufficient dietary diversity, DDS < 4), the high dietary diversity group (sufficient dietary diversity, DDS ≥ 4) exhibited a decreased risk of visual impairment (OR = 0.820, 95% CI, 0.713-0.944) and dual sensory impairment (OR = 0.751, 95% CI, 0.667-0.846). However, no statistically significant correlation was observed between dietary diversity and the presence of only hearing impairment (OR = 0.924, 95% CI, 0.815-1.047) (P < 0.05). CONCLUSIONS AND IMPLICATIONS: The synthesis of research findings suggests that following diverse dietary patterns and healthy nutritional practices may be an effective and affordable way to prevent age-related decline in visual impairment and dual sensory impairment.
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Dieta , Pérdida Auditiva , Trastornos de la Visión , Humanos , Femenino , Masculino , China/epidemiología , Estudios Transversales , Pérdida Auditiva/epidemiología , Trastornos de la Visión/epidemiología , Anciano de 80 o más Años , Estudios Longitudinales , Dieta/estadística & datos numéricos , Longevidad , Prevalencia , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Neuroinflammation and mitochondrial dysfunction play crucial roles in retinal ischemia and reperfusion (IR) injury. Recent studies have identified mitochondrial function as a promising target for immunomodulation. Empagliflozin (EMPA), an anti-diabetic drug, has exhibited great potential as both an anti-inflammatory agent and a protector of mitochondrial health. This study aimed to assess the therapeutic efficacy of EMPA in retinal IR injury. METHODS: To evaluate the protective effects of EMPA, the drug was injected into the vitreous body of mice post-retinal IR. Single-cell RNA sequencing (scRNA-seq) analysis was conducted to uncover the underlying mechanisms, and the results were further validated through in vivo and in vitro experiments. RESULTS: EMPA effectively protected retinal ganglion cells (RGCs) from IR injury by attenuating local retinal inflammation. The scRNA-seq analysis revealed that EMPA downregulated the nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) signaling pathway and restored mitochondrial dynamics by upregulating the expression of mitochondrial fusion-related genes, Mitofusin 1 (Mfn1) and optic atrophy 1 (Opa1). These findings were further corroborated by Western blotting. In vitro experiments provided additional insights, demonstrating that EMPA suppressed lipopolysaccharide (LPS)-induced cell inflammation and NLRP3 inflammasome activation. Moreover, EMPA enhanced mitochondrial fusion, neutralized mitochondrial reactive oxygen species (mtROS), and restored mitochondrial membrane potential (MMP) in BV2 microglia. Notably, genetic ablation of Mfn1 or Opa1 abolished the anti-inflammatory effects of EMPA. CONCLUSIONS: Our findings highlight the positive contribution of Mfn1 and Opa1 to the anti-inflammatory therapeutic effect of EMPA. By restoring mitochondrial dynamics, EMPA effectively mitigates microglia-mediated neuroinflammation and prevents RGC loss in retinal IR injury.
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Proteína con Dominio Pirina 3 de la Familia NLR , Daño por Reperfusión , Ratones , Animales , Enfermedades Neuroinflamatorias , Microglía/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Isquemia , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , GTP FosfohidrolasasRESUMEN
BACKGROUND: Retinal ischemia-reperfusion (RIR) injury refers to an obstruction in the retinal blood supply followed by reperfusion. Although the molecular mechanism underlying the ischemic pathological cascade is not fully understood, neuroinflammation plays a crucial part in the mortality of retinal ganglion cells. METHODS: Single-cell RNA sequencing (scRNA-seq), molecular docking, and transfection assay were used to explore the effectiveness and pathogenesis of N,N-dimethyl-3ß-hydroxycholenamide (DMHCA)-treated mice with RIR injury and DMHCA-treated microglia after oxygen and glucose deprivation/reoxygenation (OGD/R). RESULTS: DMHCA could suppress inflammatory gene expression and attenuate neuronal lesions, restoring the retinal structure in vivo. Using scRNA-seq on the retina of DMHCA-treated mice, we provided novel insights into RIR immunity and demonstrated nerve injury-induced protein 1 (Ninjurin1/Ninj 1) as a promising treatment target for RIR. Moreover, the expression of Ninj1, which was increased in RIR injury and OGD/R-treated microglia, was downregulated in the DMHCA-treated group. DMHCA suppressed the activation of the nuclear factor kappa B (NF-κB) pathways induced by OGD/R, which was undermined by the NF-κB pathway agonist betulinic acid. Overexpressed Ninj1 reversed the anti-inflammatory and anti-apoptotic function of DMHCA. Molecular docking indicated that for Ninj1, DMHCA had a low binding energy of - 6.6 kcal/mol, suggesting highly stable binding. CONCLUSION: Ninj1 may play a pivotal role in microglia-mediated inflammation, while DMHCA could be a potential treatment strategy against RIR injury.
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FN-kappa B , Daño por Reperfusión , Ratones , Animales , FN-kappa B/metabolismo , Transducción de Señal , Simulación del Acoplamiento Molecular , Oxígeno , Células Ganglionares de la Retina/patología , Daño por Reperfusión/metabolismo , Inflamación/tratamiento farmacológico , Factores de Crecimiento Nervioso , Moléculas de Adhesión Celular NeuronalRESUMEN
PURPOSE: To explore the utility of the recovery time (RT) after temporal contrast adaptation in primary open-angle glaucoma (POAG) visual function analysis, especially in severe and end-stage glaucoma, by the Erlanger Flicker Test (EFT). METHODS: This study included 80 POAG eyes (45 subjects) and 20 normal eyes (20 subjects). POAG eyes were divided into 5 groups. The diagnostic efficacy of the EFT was assessed, and the RT of POAG eyes at different stages was compared. The EFT results were compared with glaucomatous structure and function test results. A nomogram was developed to predict disease progression by the RT and structural indicators. RESULTS: In the normal eyes, as the test contrast increased, the RT gradually decreased. The EFT test-retest reproducibility was good, with intraclass correlation coefficient values of 0.6 (P < 0.05) for each test contrast. At 12%, 25%, and 35% contrast, the RT in the severe and end-stage glaucoma eyes was significantly prolonged compared with the control group (P < 0.05). The RT at different contrasts was significantly correlated with visual acuity, mean defect, mean sensitivity, and general and individual quadrant optic nerve fiber layer thickness (P ≤ 0.001). The receiver operating curve indicated that RT12% showed the best overall area under the curve (0.863). We included RT25% and average optic nerve fiber layer thickness in constructing the nomogram. POAG eyes were further divided into 8 stages. According to the probability distribution, this model showed good performance for visual function analysis in advanced glaucoma. CONCLUSIONS: Combined with traditional glaucomatous structural and functional parameters, the EFT can be used in the diagnosis and visual function analysis of POAG, especially for severe and end-stage glaucoma. It could be a potential test for disease staging in severe and end-stage glaucoma.
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Glaucoma de Ángulo Abierto , Glaucoma , Estudios Transversales , Humanos , Presión Intraocular , Reproducibilidad de los Resultados , Tomografía de Coherencia Óptica , Campos VisualesRESUMEN
Based on the LiNbO3 (LN) single crystal thin film prepared using Ar+ etching, an LN thin film memristor was fabricated by oxygen annealing. Atomic force microscope, scanning electron microscope and electron paramagnetic resonance test results show that the method uniformly reduces the amount of oxygen vacancies on the surface of the material. The current-voltage scanning (I-V scanning), retention and endurance test results show that this method effectively reduces the possibility of breakdown and increases the retention and endurance performance of the device. By adjusting the parameters of the electric pulse, the annealed sample successfully emulated spike-rate dependent plasticity, pulse-paired facilitation, post-tetanic potentiation, Ebbinghaus forgetting curve and the spike-time dependent plasticity. These results indicate that the device prepared herein could be used as an electronic synapse in the field of brain-like neuromorphic computing systems.
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AIM: The value of top-hat procedure during loop electrosurgical excision procedure (LEEP) for squamous intraepithelial lesions had remained controversial. This study aimed to evaluate whether top-hat specimens positive for cervical intraepithelial neoplasia (CIN) on histopathology can serve as an independent risk factor to predict treatment failure. METHODS: We reviewed the medical records of patients who underwent LEEP and top-hat procedures in Peking University First Hospital between 2011 and 2016 and collected their follow-up data until January 2019. We compared the pathological risk factor of treatment failure. Multivariate analysis was carried out to clarify the independent determinant of treatment failure. A Cox model was used to assess the influence of different variables on cumulative treatment failure rates. RESULTS: This study included 295 cases for short-term treatment failure, and among them, 178 cases were used to study the long-term. The presence of CIN in top-hat was relevant to short-term treatment failure (OR = 9.64, 95% CI 2.55-36.4) despite a clear margin. On multivariate analysis, top-hat result (OR = 3.58, 95% CI 1.30-9.89), age ≥ 50 (OR = 10.2, 95%CI 3.64-28.3) and post-treatment HPV 16/18 infection (OR = 2.35, 95%CI 1.19-4.63) were independent risk factors in predicting short-term failure. In the Cox model, these factors were also associated with higher cumulative failure rates. CONCLUSION: The current study supported the predictive value of top-hat procedure in short-term failure after LEEP. Typically, women with positive top-hat need closer follow-up despite their negative margin status. Older women with positive top-hat findings and HPV 16/18 infections after the treatment suffer a higher risk of short-term failure.
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Lesiones Intraepiteliales Escamosas , Neoplasias del Cuello Uterino , Anciano , Electrocirugia , Femenino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Insuficiencia del Tratamiento , Neoplasias del Cuello Uterino/cirugíaRESUMEN
BACKGROUND: Blindness and vision loss (BVL) is a major global health issue affecting older adults, but its burden in transition countries has received limited attention. Therefore, we aimed to assess the trends in the burden of BVL among older adults between 1990 and 2019 across Brazil, Russia, India, China, and South Africa (BRICS), and predict the burden by 2040. METHODS: Data on BVL and its related causes were obtained from the Global Burden of Disease 2019 study. We investigated the temporal trends by calculating the average annual percentage change using joinpoint regression analysis. Subsequently, we performed Bayesian age-period-cohort modeling to estimate the burden of BVL and its related causes by 2040. RESULTS: Most BRICS countries experienced a significant decline (p < 0.05) in age-standardized prevalence rates, and the decreasing trends tend to continue. However, by 2040, the number of BVL cases is expected to increase by approximately 50% across BRICS, with an estimated approximately 192, 170, 25, 17, and 7 million cases in China, India, Russia, Brazil, and South Africa, respectively. The related ranks of BVL causes are also estimated to change in the future, particularly in India. CONCLUSIONS: The different burdens and trends of BVL across BRICS reflected the different stages of population health transition. Effective eye disease prevention requires appropriate public health interventions. Developing effective health policies and services for older adults is urgently needed in BRICS countries.
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Ceguera , Atención a la Salud , Humanos , Anciano , Prevalencia , Teorema de Bayes , Ceguera/epidemiología , Ceguera/etiología , China/epidemiología , India/epidemiología , Sudáfrica/epidemiología , Brasil/epidemiologíaRESUMEN
Purpose: To characterize the fundus tessellated density (FTD) in highly myopic glaucoma (HMG) and high myopia (HM) for discovering early signs and diagnostic markers. Methods: This retrospective cross-sectional study included hospital in-patients with HM (133 eyes) and HMG (73 eyes) with an axial length ≥26 mm at Zhongshan Ophthalmic Center. Using deep learning, FTD was quantified as the average exposed choroid area per unit area on fundus photographs in the global, macular, and disc regions. FTD-associated factors were assessed using partial correlation. Diagnostic efficacy was analyzed using the area under the curve (AUC). Results: HMG patients had lower global (0.20 ± 0.12 versus 0.36 ± 0.09) and macular FTD (0.25 ± 0.14 vs. 0.40 ± 0.09) but larger disc FTD (0.24 ± 0.11 vs. 0.19 ± 0.07) than HM patients in the tessellated fundus (all P < 0.001). In the macular region, nasal FTD was lowest in the HM (0.26 ± 0.13) but highest in the HMG (0.32 ± 0.13) compared with the superior, inferior, and temporal subregions (all P < 0.05). A fundus with a macular region nasal/temporal (NT) FTD ratio > 0.96 (AUC = 0.909) was 15.7 times more indicative of HMG than HM. A higher macular region NT ratio with a lower horizontal parapapillary atrophy/disc ratio indicated a higher possibility of HMG than HM (AUC = 0.932). Conclusions: FTD differs in degree and distribution between HMG and HM. A higher macular NT alone or with a lower horizontal parapapillary atrophy/disc ratio may help differentiate HMG. Translational Relevance: Deep learning-based FTD measurement could potentially assist glaucoma diagnosis in HM.
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Aprendizaje Profundo , Demencia Frontotemporal , Glaucoma , Miopía , Humanos , Estudios Transversales , Estudios Retrospectivos , Glaucoma/complicaciones , Glaucoma/diagnóstico , Miopía/complicaciones , Miopía/diagnóstico , Atrofia , CoroidesRESUMEN
Importance: Visual impairment in working-age individuals can affect their general health and employment prospects, leading to decreased social and economic productivity and increased poverty rates. Nonetheless, investigations in this population appear to be limited. Objective: To investigate the trends of visual impairment prevalence and disability-adjusted life-years (DALYs) in working-age individuals from 1990 to 2019. Design, Setting, and Participants: This cross-sectional, population-based study used data for individuals of working age (15-64 years) from 204 countries and territories obtained from the Global Burden of Disease 2019 study. The data analysis was performed between May 1 and 10, 2023. Exposure: Visual impairment, defined as visual acuity of less than 6/18 (20/60) or near visual acuity of less than 6/12 (20/40) distance equivalent as determined by Snellen chart. Main Outcomes and Measures: Trends of visual impairment prevalence, DALYs, and corresponding estimated annual percent changes (EAPCs) from 1990 to 2019 were stratified according to region, nation, and sociodemographic index (SDI). Results: There were 437â¯539â¯484 (95% uncertainty interval [UI], 325â¯463â¯851-575â¯573â¯588) prevalent cases of visual impairment globally (53.12% female and 46.88% male) in 2019, representing an increase of 91.46% from 1990 (prevalent cases, 228â¯530â¯964; 95% UI, 172â¯515â¯833-297â¯118â¯596). Over 3 decades, visual impairment-associated DALYs increased from 7â¯601â¯852 (95% UI, 5â¯047â¯030-11â¯107â¯897) to 12â¯563â¯276 (95% UI, 8â¯278â¯866-18â¯961â¯723). Among the 5 SDI groups, the low-SDI group had the largest increase in DALYs (898 167 [95% UI, 597 161-1 301 931] in 1990 to 1 634 122 [95% UI, 1 079 102-2 444 381] in 2019). Regionally, the greatest increase in prevalence was observed in Eastern Europe (EAPC, 0.10; 95% CI, 0.02-0.19). Among all countries and territories, Nepal had the highest national prevalence of visual impairment per 100â¯000 population in 2019 (26â¯008.45; 95% UI, 19â¯987.35-32â¯482.09), while South Sudan had the highest DALY rate per 100â¯000 population (480.59; 95% UI, 316.06-697.06). Conclusions and Relevance: Despite the mild decrease in visual impairment prevalence rates in less-developed countries, these findings suggest that the number of prevalent cases globally has increased substantially, with discernible unfavorable patterns in developed regions. The findings support the notion that visual impairment in working-age individuals is a growing global health challenge. A better understanding of its epidemiology may facilitate the development of appropriate measures for prevention and treatment from both medical and social perspectives.
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Carga Global de Enfermedades , Salud Global , Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Años de Vida Ajustados por Calidad de Vida , Estudios Transversales , Prevalencia , Trastornos de la Visión/epidemiología , IncidenciaRESUMEN
AIMS: Elevated fasting plasma glucose (FPG) levels have been associated with visual impairment. Recognising global patterns of high FPG level exposure can facilitate the prevention and treatment of related visual impairment. We aimed to assess the trends of the visual impairment burden attributable to high FPG levels globally, regionally, nationally, and by income level. METHODS: We obtained data on the visual impairment burden attributable to high FPG levels from the Global Burden of Disease Study 2019. We evaluated the trends of related disability-adjusted life-years (DALYs) from 1990 to 2019 through joinpoint regression analysis and calculated the annual percentage change (APC) and average APC (AAPC). Countries/territories were categorised into high-, upper-middle-, lower-middle-, and low-income groups based on the 2019 World Bank criteria. RESULTS: The age-standardised rate of DALYs due to visual impairment attributable to high FPG levels significantly increased globally, from 6.75 (95% uncertainty interval [UI], 1.55-15.79) in 1990 to 8.44 per 100,000 population (95% UI, 2.00-19.63) in 2019 (AAPC, 0.79; 95% confidence interval [CI], 0.69-0.89; p < 0.001). The largest increases were observed in high-income (AAPC, 0.73; 95% CI, 0.60-0.85) and lower-middle-income countries/territories (AAPC, 0.68; 95% CI, 0.62-0.73). In 2019, lower-middle-income countries/territories had the highest age-standardised DALY rate (18.94 per 100,000 population; 95% UI, 4.39-43.98), whereas high-income countries/territories had the lowest (2.97 per 100,000 population; 95% UI, 0.75-6.74). CONCLUSIONS: The visual impairment burden associated with elevated FPG levels has increased significantly, necessitating enhanced public health prevention measures, clinical management, and treatment to mitigate adverse outcomes.
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Background: To explore the clinical characteristics of Posner-Schlossman syndrome (PSS) patients in China, especially the risk factors associated with the dynamic changes of corneal endothelial cell (CEC) density and retinal nerve fiber layer (RNFL) thickness during the course of the disease. Methods: In this retrospective cohort study, patients consequently suffering from PSS were recruited. Patients data including gender, age of onset, frequency of attack, and disease duration. We performed detailed ophthalmology examinations including intraocular pressure (IOP), best-corrected visual acuity (BCVA), slit-lamp examination, optical coherence tomography (OCT), assessing RNFL thickness, and determined CEC density in the outpatient department. The unaffected eyes served as control. Results: We recruited 121 patients (eyes, n = 125), including 69 (57.0%) males and 52 (43.0%) females with Posner-Schlossman syndrome. The age of first-onset was 33.81 ± 13.63 years old. The majority of these patients were aged 20-50 years (80.2%). The peak IOP was 47.67 ± 13.31 mmHg in the affected eyes. The frequency of PSS attack was 2.7 ± 3.7 times per year. The disease duration was 9.5 ± 10.4 years. Among all patients, there were 27 (22.31%) patients with a history of digestive disorders, 25 (20.66%) patients with a history of allergies, and 24 (19.83%) patients with a history of infectious disease. In the affected eyes, CEC density (2532.94 ± 490.83/mm2 vs. 2777.13 ± 356.87/mm2, p < 0.001), the RNFL thickness of four quadrants (superior 105.46 ± 29.86 µm vs. 121.33 ± 17.30 µm, p < 0.001; temporal 74.58 ± 22.21 µm vs. 81.94 ± 18.20 µm, p = 0.009; inferior 110.50 ± 33.42 µm vs. 128.29 ± 14.39 µm, p < 0.001; nasal 54.85 ± 14.48 µm vs. 63.49 ± 15.40 µm, p < 0.001) and central papillary (87.11 ± 21.18 µm vs. 99.18 ± 7.97 µm, p < 0.001) were significantly reduced compared to the fellow eyes. The disease duration and recurrent frequency were significantly associated with CEC density (p < 0.001 and p = 0.029) and the disease duration was significantly associated with RNFL thickness (p = 0.002). Conclusions: In this study, CEC loss and RNFL thinning were present in the affected eyes. Our results indicated that disease duration and recurrent frequency played an important role in the progression of PSS.
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Glaucoma de Ángulo Abierto , Fibras Nerviosas , Masculino , Femenino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Retina/diagnóstico por imagen , Presión Intraocular , Tomografía de Coherencia Óptica/métodosRESUMEN
AIM: To evaluate trends in glaucoma procedures at the Peking University Eye Center in 2016-2020. METHODS: A retrospective search of all glaucoma procedures performed at our institution were performed. Data were analyzed by calculating the absolute numbers and relative weightage of each procedure per year. RESULTS: The average age of glaucoma patients undergoing surgical procedures was 62.33±17.87y, and 55% were women. From 2016 to 2019, the number of surgical procedures performed in glaucoma patients showed an overall upward trend from 749 to 1460, although it decreased slightly in 2020 (n=1393), probably due to the COVID-19 pandemic. The number of trabeculectomies did not change significantly in 2016 (n=161) to 2018 (n=164) but decreased in 2019 (n=139) to 2020 (n=121), indicating a reduction in its relative weightage among glaucoma procedures (from 21.50% to 8.69%). The number of glaucoma drainage device implantations and minimally invasive glaucoma surgeries both increased (50 and 58 respectively in 2019), except in 2020. The number of transscleral cyclophotocoagulation procedures was relatively stable, increasing until 2017 (n=218) and then decreasing. Cataract surgeries with or without glaucoma procedures accounted for a large number of the total surgeries, increasing from 247 (32.97%) in 2016 to 967 (69.42%), among which cataract extraction combined with goniosynechialysis was the most frequent. CONCLUSION: The overall increase in the number of operating room-based surgical procedures is significant. Trabeculectomy is one of the most commonly performed procedures, despite the relative decline in its weightage. Other procedures, including use of glaucoma drainage devices and mini shunts and minimally invasive glaucoma surgeries, are gaining greater acceptance. Notably, lens-related surgery plays an important role in glaucoma management.
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Immune checkpoint blockade (ICB) therapy targeting the programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) axis has achieved considerable success in treating a wide range of cancers. However, most patients with pancreatic cancer remain resistant to ICB. Moreover, there is a lack of optimal biomarkers for the prediction of response to this therapy. Palmitoylation is mediated by a family of 23 S-acyltransferases, termed zinc finger Asp-His-His-Cys-type palmitoyltransferases (ZDHHC), which precisely control various cancer-related protein functions and represent promising drug targets for cancer therapy. Here, we revealed that tumor cell-intrinsic ZDHHC9 was overexpressed in pancreatic cancer tissues and associated with impaired anti-tumor immunity. In syngeneic pancreatic tumor models, the knockdown of ZDHHC9 expression suppressed tumor progression and prolonged survival time of mice by modifying the immunosuppressive ('cold') to proinflammatory ('hot') tumor microenvironment. Furthermore, ZDHHC9 deficiency sensitized anti-PD-L1 immunotherapy mainly in a CD8+ T cell dependent manner. Lastly, we employed the ZDHHC9-siRNA nanoparticle system to efficiently silence ZDHHC9 in pancreatic tumors. Collectively, our findings indicate that ZDHHC9 overexpression in pancreatic tumors is a mechanism involved in the inhibition of host anti-tumor immunity and highlight the importance of inactivating ZDHHC9 as an effective immunotherapeutic strategy and booster for anti-PD-L1 therapy against pancreatic cancer.
Asunto(s)
Neoplasias Pancreáticas , Microambiente Tumoral , Animales , Ratones , Aciltransferasas/genética , Inmunoterapia , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias PancreáticasRESUMEN
PURPOSE: To assess the distribution pattern of aerosol in the aspect of time and direction during the intraocular pressure (IOP) measurement by air-puff non-contact tonometer (NCT) and further offer references for protection from coronavirus disease-19 (COVID-19) in the routine ophthalmic examination. METHOD: A single-center observational study was conducted in the ophthalmology clinics of Peking University Third Hospital. Two air quality detectors were equipped to assess the generated particulate matter (PM) concentration simultaneously within 30â s after IOP measurement in the outpatient hall. Detector A was fixed next to the NCT as a reference, while Detector B was fixed 1 meter away. The participants were divided into two groups depending on the position of Detector B. The generation of aerosol was compared within different groups and time intervals. RESULTS: 144 participants were enrolled in the final analysis. At a 1â m distance from the NCT, the PM2.5 concentration significantly increased at the 30â s (Z = 2.898, Bonferroni-corrected P = 0.038) while the PM10 concentration increased immediately after the IOP measurement (Z = 2.967, Bonferroni-corrected P = 0.030). The PM2.5 and PM10 concentrations at 1â m were significantly higher immediately (Z = -2.183, P = 0.029; Z = -2.502, P = 0.012) and 30â s (Z = -2.021, P = 0.043; Z = -2.071, P = 0.038) after the IOP measurements when the Detector B was vertical to the air jet on the lateral side. CONCLUSIONS: NCT may produce aerosol after the IOP measurement by air-puff. The generated PM2.5 had a prolonged existence compared with PM10 at a 1â m distance. The lateral side of the air-puff direction may be of higher exposure risk to aerosol.
Asunto(s)
COVID-19 , Tonometría Ocular , COVID-19/epidemiología , Humanos , Presión Intraocular , Material Particulado , Aerosoles y Gotitas Respiratorias , Tonometría Ocular/métodosRESUMEN
The demands on novel and sustainable techniques for vegetable waste (VW) valorization continues to increase during the past few decades due to the growing waste production under the flourishing vegetable industries. In this study, Chinese cabbage residues were hydrothermal carbonization (HTC) at 180, 200, 220 and 240 °C for 2 to 6 h to explore the impacts of process parameters on the characteristics of hydrochars and hydrolysates and their feasibility in sustainable agriculture. Results indicated that hydrothermal temperature had a greater impact on cabbage residue hydrolysis than the residence time. With the rising reaction severity, hydrochars became more alkaline with higher amount of ash and carbon (C), while the pH and dissolved organic nitrogen (DON) and NH4+-N in the hydrolysate were gradually reduced. The thermogravimetric analysis (TG-DTG) indicated that organic constitutions in the feedstock went through incomplete decomposition. Although the recalcitrance index (R50) steadily increased through HTC (0.37-0.46), hydrochars were unstable and would not applicable for carbon sequestration. Furthermore, hydrochars and hydrolysate would be optimal media for plants seedling and growth for the abundant nutrients and dissolved organic compounds but reduced phytotoxicity. In conclusion, these results showed that HTC is highly applicable for vegetable waste management for sustainable agriculture.
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Brassica , Carbono , Agricultura , China , TemperaturaRESUMEN
This study aimed to comprehensively understand the proteomic characteristics and modulation of the neural microenvironment with N-methyl-d-aspartate (NMDA)-induced neuronal degeneration in the retina and optic nerve at 12 h after intravitreal injection of 40 nmol NMDA. Male Sprague-Dawley rats were sacrificed at 12 h after intravitreal injection of 40 nmol NMDA. PBS-injected eyes served as controls. The key cell death-linked proteins from the retina and optic nerve tissues were assessed by a mass spectrometry-based label-free approach. In proteomics analysis, we identified 3532 proteins in retinal tissues and 2593 proteins in optic nerve tissues. The ACSL3 (Q63151) and Prnp (P13852) proteins were upregulated in the NMDA-damaged retina and connected with ferroptosis. The Gabarapl2 (P60522) protein was upregulated in NMDA-damaged optic nerves and connected with autophagy. We performed parallel reaction monitoring (PRM) to validate the liquid chromatography-tandem mass spectrometry (LC-MS/MS) results. Data are available ProteomeXchange with identifiers PXD022466 (label-free quantification) and PXD022729 (PRM validation). SIGNIFICANCE: Excitotoxicity is one of the pathogeneses of various retinal disorders, including glaucoma, retinal ischemia-reperfusion and traumatic optic neuropathy. This study indicated that ferroptosis may be linked to pathological cell death in the retina with NMDA insult. Autophagy may be induced by NMDA overstimulation in both the optic nerve and retina. Regulating these types of death simultaneously may provide the maximum benefit for retinal disease therapy.