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It has been widely acknowledged that high temperatures and heatwaves promote ozone concentration, worsening the ambient air quality. However, temperature can impact ozone via multiple pathways, and quantifying each path is challenging due to environmental confounders. In this study, we frame the problem as a treatment-outcome issue and utilize a machine learning-aided causal inference technique to disentangle the impact of temperature on ozone formation. Our approach reveals that failing to account for the covariations of solar radiation and other meteorological factors leads to an overestimation of the O3-temperature response. Through process evaluation, we find that temperature influences local ozone formation mainly by accelerating chemical reactions and enhancing precursor production and changing boundary layer heights. The O3 response to temperature via enhancing soil NOx and changing relative humidity and wind field is however observable. A better appreciation of O3-temperature response is critical for improving air quality regulation in the warming future.
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Purpose: This study aimed to investigate the antioxidative and neuroprotective effects of DJ-1 in mitigating retinal ganglion cell (RGC) damage induced by high glucose (HG). Methods: A diabetic mouse model and an HG-induced R28 cell model were employed for loss- and gain-of-function experiments. The expression levels of apoptosis and oxidative stress-related factors, including Bax, Bcl-2, caspase3, Catalase, MnSOD, GCLC, Cyto c, and GPx-1/2, were assessed in both animal and cell models using Western blotting. Retinal structure and function were evaluated through HE staining, electroretinogram, and RGC counting. Mitochondrial function and apoptosis were determined using JC-1 and TUNEL staining, and reactive oxygen species (ROS) measurement. Results: In the mouse model, hyperglycemia resulted in reduced retinal DJ-1 expression, retinal structural and functional damage, disrupted redox protein profiles, and mitochondrial dysfunction. Elevated glucose levels induced mitochondrial impairment, ROS generation, abnormal protein expression, and apoptosis in R28 cells. Augmenting DJ-1 expression demonstrated a restoration of mitochondrial homeostasis and alleviated diabetes-induced morphological and functional impairments both in vivo and in vitro. Conclusion: This study provides novel insights into the regulatory role of DJ-1 in mitochondrial dynamics, suggesting a potential avenue for enhancing RGC survival in diabetic retinopathy.
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PURPOSE: To report a rare case of fungal keratitis caused by Cryptococcus neoformans, highlighting its unique morphological features using in vivo confocal microscopy (IVCM). METHODS: This was a retrospective case report. A 66-year-old man presented with foreign body sensation and blurred vision in his left eye for over 10 months. RESULTS: His best-corrected visual acuity was 20/20. Slit-lamp examination revealed a gray-white lesion approximately 4-5 mm in the superficial layer of the central cornea without epithelial defects. The IVCM images revealed numerous round or round-like pathogens, each with a central highly reflective body surrounded by a dark ring, ranging in size from 5 to 30 µm, and to a maximum of 85 µm, observed in the corneal epithelium and superficial stroma. No obvious inflammatory cell infiltration was observed in the lesions or endothelium. C. neoformans infection was confirmed. The round pathogens completely disappeared after 8 weeks of treatment with topical amphotericin B and voriconazole eye drops. CONCLUSION: Fungal keratitis caused by C. neoformans is rare and easily overlooked due to atypical clinical signs and symptoms. This case reports the unique morphological features of C. neoformans in the cornea using IVCM for the first time, facilitating rapid, noninvasive auxiliary diagnosis of C. neoformans keratitis and treatment follow-up.
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PURPOSE: Complications such as explosive choroidal hemorrhage, residual cortex, and capsule rupture often occur during intraocular surgery combined with penetrating keratoplasty (PKP) due to poor maintenance of the anterior chamber. To address these challenges, we have innovatively utilized a sterile polyethylene instrument cover to temporarily reconstruct the anterior chamber. METHODS: In this report, we describe a technique where a 'temporary corneal patch' was created from a sterile instrument cover, using a trephine to ensure a diameter approximately 1-2 mm wider than the corneal bed or perforation. This patch was then sutured into the host corneal bed or the perforation with 10-0 nylon sutures during intraocular surgery combined with PKP. Each case was evaluated for surgical efficacy and complications. RESULTS: We successfully applied this technique in three cases of combined corneal transplantation surgery. In two cases, PKP, phacoemulsification, and intraocular lens implantation were successfully performed. In the third case, PKP, vitrectomy, and other intraocular procedures were performed. No intraoperative or postoperative complications were observed. CONCLUSION: The use of a sterile polyethylene material as a temporary corneal patch for anterior chamber reconstruction represents a safe, effective, and cost-efficient approach for intraocular surgery combined with PKP or posterior segment surgery as a keratoprosthesis.
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Glaucoma is a chronic ocular disease characterized by optic atrophy and visual field defect. The main risk factor for glaucoma onset and progression is elevated intraocular pressure, which is caused by increased aqueous humor outflow resistance. Currently, the primary method for glaucoma therapy is the use of intraocular pressure lowering drugs. However, these drugs, when administered through eye drops, have low bioavailability, require frequent administration, and often result in adverse effects. To overcome these challenges, the application of nanotechnology for drug delivery has emerged as a promising approach. Nanoparticles can physically adsorb, encapsulate, or chemically graft drugs, thereby improving their efficacy, retention time, and reducing adverse reactions. Moreover, nanotechnology has opened up new avenues for ocular administration. This article provides a comprehensive review of nano systems for intraocular pressure lowering drugs, encompassing cholinergic agonists, ß-adrenergic antagonists, α-adrenergic agonists, prostaglandin analogs, carbonic anhydrase inhibitors, Rho kinase inhibitors, and complex preparations. The aim is to offer novel insights for the development of nanotechnology in the field of intraocular pressure lowering drugs.
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The Tibetan Plateau, known as the "Third Pole", is susceptible to ground-level ozone (O3) and fine particulate matter (PM2.5) pollution due to its unique high-altitude environment. This study constructed random forest regression models using multi-source data from ground measurements and meteorological satellites to predict variations in ground-level O3 and PM2.5 concentrations and their influencing factors across seven major cities in the Tibetan Plateau over two-year periods. The models successfully reproduced O3 and PM2.5 levels with satisfactory R-squared values of 0.71 and 0.73, respectively. Results reveal combustion-related carbon monoxide (CO) and nitrogen dioxide (NO2) as the most substantial influences on O3 and PM2.5 concentrations. Solar radiation, geographical factors, and meteorological variables also played crucial roles in driving pollutant variations. Conversely, transport-related and human activity factors exhibited relatively lower significance. High O3 and PM2.5 pollution occurred during pre-monsoon and post-monsoon/winter seasons, driven by solar radiation and emissions, respectively. While CO consistently contributed across cities and seasons, key influencing factors varied locally. This study unveils the key driving forces governing air pollutant variations across the Tibetan Plateau, shedding light on complex atmospheric processes in this unique high-altitude region.
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Purpose: Although it is now understood that most antiglaucoma surgeries fail because of scarring of the filtering tract, the underlying mechanism remains to be elucidated. The present study investigated the mechanism by which the interleukin (IL)-22/IL-22 receptor alpha 1 (IL-22RA1) signaling pathway regulates scar formation in glaucoma patients. Method: A total of 31 glaucoma patients who underwent trabeculectomy surgery with uncontrollable intraocular pressure because of scarring and 19 strabismus patients as the control patient group were included in the present study. ELISA was performed to measure the content of IL-22 in peripheral blood. Serum from patients was used to incubate human Tenon's capsule fibroblasts (HTFs) cells and IL-22 antibody rescued the effect of IL-22 on the biological functions. qPCR and Western blot were performed to determine IL-22RA1 mRNA and protein expression levels. Flow cytometry was performed to assess the cell cycle distribution and the Cell Counting Kit-8 assay was used to analyze cell proliferation. Results: The ELISA assay revealed that the serum IL-22 level of glaucoma patients was significantly higher than the healthy group (29.80 ± 5.1 ng/µL vs. 5.21 ± 0.9 ng/µL). After incubation with patient serum, the proliferation and activation of human Tenon fibroblasts (HTFs) were promoted. IL-22 mediated the biological function of HTFs via directly binding IL-22RA1. Moreover, transfection of the siR-IL-22RA1 or IL-22RA1 gene resulted in significant antifibrosis or profibrosis in HTFs. When a signal transducer and activator of transcription (STAT) 3 inhibitor (BAY) was introduced to the IL-22RA1 overexpression group, IL-22-induced proliferation was reduced in HTFs. Additionally, glaucoma patients had increased levels of IL-22 expression following surgery. Conclusions: The IL-22/IL-22RA1/STAT3 signaling pathway promoted fibroblast cell proliferation and alpha-smooth muscle actin, potentially regulating fibrosis in glaucoma filtration tracts. Our results provide hitherto undocumented insights into the pathophysiology of postoperative scarring.
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Proliferação de Células , Fibroblastos , Fibrose , Glaucoma , Interleucina 22 , Interleucinas , Receptores de Interleucina , Fator de Transcrição STAT3 , Transdução de Sinais , Cápsula de Tenon , Humanos , Fibroblastos/metabolismo , Cápsula de Tenon/metabolismo , Fator de Transcrição STAT3/metabolismo , Glaucoma/patologia , Glaucoma/metabolismo , Interleucinas/metabolismo , Masculino , Feminino , Receptores de Interleucina/metabolismo , Pessoa de Meia-Idade , Células Cultivadas , Adulto , Idoso , TrabeculectomiaRESUMO
PURPOSE: To evaluate the characteristic of corrective epithelial thickness after femtosecond laser-assisted lenticule intrastromal keratoplasty (LIKE) to correct moderate-to-high hyperopia. METHODS: The prospective case series study of the LIKE procedure was performed to correct moderate-to-high hyperopia. The epithelial thickness map was generated by anterior segment optical coherence tomography (AS-OCT) in the corneal central 9-mm zone. Keratometry and corneal higher order aberrations were analyzed by Pentacam (Oculus Optikgeräte GmbH) preoperatively and postoperatively. RESULTS: In the 26 eyes of 13 participants who underwent the LIKE procedure for moderate-to-high hyperopia, the attempted spherical equivalence (SEQ) was +6.50 ± 1.09 diopters (D). Compared to the preoperative epithelial thickness maps, the postoperative epithelial thickness had become significantly thinner in the central 5-mm zone; the difference was 6 to 7 µm. The paracentral epithelium performed nonuniform remodeling; the thinnest epithelial thickness was located in the inferotemporal section, which has the greatest difference from the superonasal; the difference between these two was approximately 3 µm. Through correlation analysis, it was found that the sections with thinner epithelium were significantly related to corneal curvature and corneal vertical coma. CONCLUSIONS: The LIKE procedure can be used to correct moderate-to-high hyperopia. This study further indicated the epithelial remodeling characteristic after the LIKE procedure: the central and paracentral corneal epithelial thickness becomes thinner, and the epithelial thickness distributes non-uniformly, which may be the important factor of the postoperative curvature asymmetric distribution and induction of corneal vertical coma. [J Refract Surg. 2024;40(5):e321-e327.].
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Substância Própria , Topografia da Córnea , Epitélio Corneano , Hiperopia , Refração Ocular , Tomografia de Coerência Óptica , Acuidade Visual , Humanos , Hiperopia/cirurgia , Hiperopia/fisiopatologia , Estudos Prospectivos , Substância Própria/cirurgia , Substância Própria/patologia , Masculino , Feminino , Adulto , Acuidade Visual/fisiologia , Epitélio Corneano/cirurgia , Epitélio Corneano/patologia , Refração Ocular/fisiologia , Pessoa de Meia-Idade , Lasers de Excimer/uso terapêutico , Adulto Jovem , Aberrações de Frente de Onda da Córnea/fisiopatologia , Cirurgia da Córnea a Laser/métodos , Oftalmopatias HereditáriasRESUMO
Ground-level ozone (O3) pollution poses significant threats to both human health and air quality. This study uses ground observations and satellite retrievals to explore the spatiotemporal characteristics of ground-level O3 in Zhejiang Province, China. We created data-driven machine learning models that include meteorological, geographical and atmospheric parameters from multi-source remote sensing products, achieving good performance (Pearson's r of 0.81) in explaining regional O3 dynamics. Analyses revealed the crucial roles of temperature, relative humidity, total column O3, and the distributions and interactions of precursor (volatile organic compounds and nitrogen oxides) in driving the varied O3 patterns observed in Zhejiang. Furthermore, the interpretable modeling quantified multifactor interactions that sustain high O3 levels in spring and autumn, suppress O3 levels in summer, and inhibit O3 formation in winter. This work demonstrates the value of a combined approach using satellite and machine learning as an effective novel tool for regional air quality assessment and control.
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BACKGROUND: Trabecular meshwork (TM) dysfunction-induced elevation of intraocular pressure has been identified as the main risk factor of irreversible optic nerve injury in Primary openangle glaucoma (POAG). Increasing evidences suggest that microRNA (miRNA) plays a vital role in the pathogenesis of POAG. This study aims to construct a miRNA-mRNA regulatory network and identify biomarkers for POAG. METHODS: miRNAs and mRNAs expression profiling of TM samples from controls and POAG patients were assessed through microarray analysis. Target genes of differentially expressed miRNAs (DEmiRNAs) were predicted by miEAA and miRNet. Then GO and KEGG pathway analysis of differentially expressed mRNAs (DEmRNAs) were performed. PPI of top 30 hub genes was identified and miRNA-mRNA network was established by STRING database and Cytoscape software. GSE27276 and GSE105269 datasets were used to verify the expression of hub genes and to predict potential biomarkers in TM and aqueous humor (AH) for POAG, respectively. Finally, GSEA analysis was conducted to estimate the main signaling pathway of POAG pathogenesis. RESULTS: A total of 29 up-regulated and 7 down-regulated miRNAs, 923 up-regulated and 887 down-regulated mRNAs were identified in TM of POAG compared with controls. Target genes and DEmRNAs were mainly enriched in nitric oxide biosynthetic process, vasopressin-regulated water reabsorption, and so on. Through miRNA-mRNA network construction, top 30 hub genes were regulated by 24 DEmiRNAs. 8 genes were aberrantly expressed in dataset GSE27276. 3 genes (CREB1, CAPZA2, SLC2A3) and 2 miRNAs (miR-106b-5p, miR-15a-5p) were identified as potential biomarkers for POAG in TM and AH, respectively. GSEA analysis revealed that these 3 genes modulated POAG through different pathways. CONCLUSION: In this study, construction of miRNA-mRNA network and identification of biomarkers provide a novel insight into the pathogenesis, early diagnosis and treatment for POAG.
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Glaucoma de Ângulo Aberto , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Glaucoma de Ângulo Aberto/genética , Biomarcadores/metabolismo , Humor Aquoso/metabolismo , Redes Reguladoras de GenesRESUMO
BACKGROUND: Mesenchymal stem cells (MSCs) have shown promising potential in allograft survival. However, few reports have focused on comparing the immunosuppressive capacity of MSCs from different sources and administered via different routes in inhibiting transplant rejection. Moreover, virtually nothing is known about the role of MSCs in the regulation of graft neovascularization and lymphangiogenesis. In this study, we compared the efficacy of human adipose MSCs (hAD-MSCs) and human umbilical cord MSCs (hUC-MSCs) in vitro and in corneal transplantation models to explore the underlying molecular mechanisms and provide a powerful strategy for future clinical applications. METHODS: hAD-MSCs and hUC-MSCs were generated, and their self-renewal and multi-differentiation abilities were evaluated. The inhibitory effect of human MSCs (hMSCs) was examined by T-cell proliferation assays with or without transwell in vitro. Two MSCs from different sources were separately adoptively transferred in mice corneal transplantation (5 × 105 or 1 × 106/mouse) via topical subconjunctival or intravenous (IV) routes. Allograft survival was evaluated every other day, and angiogenesis and lymphomagenesis were quantitatively analyzed by immunofluorescence staining. The RNA expression profiles of hMSCs were revealed by RNA sequencing (RNA-seq) and verified by quantitative real-time PCR (qRTâPCR), western blotting or ELISA. The function of the differentially expressed gene FAS was verified by a T-cell apoptosis assay. RESULTS: hAD-MSCs induced stronger immunosuppression in vitro than hUC-MSCs. The inhibitory effect of hUC-MSCs but not hAD-MSCs was mediated by cell-cell contact-dependent mechanisms. Systemic administration of a lower dose of hAD-MSCs showed better performance in prolonging corneal allograft survival than hUC-MSCs, while subconjunctival administration of hMSCs was safer and further prolonged corneal allograft survival. Both types of hMSCs could inhibit corneal neovascularization, while hAD-MSCs showed greater superiority in suppressing graft lymphangiogenesis. RNA-seq analysis and confirmation experiments revealed the superior performance of hAD-MSCs in allografts based on the lower expression of vascular endothelial growth factor C (VEGF-C) and higher expression of FAS. CONCLUSIONS: The remarkable inhibitory effects on angiogenesis/lymphangiogenesis and immunological transplantation effects support the development of hAD-MSCs as a cell therapy against corneal transplant rejection. Topical administration of hMSCs was a safer and more effective route for application than systemic administration.
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Transplante de Córnea , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Camundongos , Animais , Fator C de Crescimento do Endotélio Vascular/farmacologia , Linfangiogênese , Sobrevivência de Enxerto , Cordão Umbilical , Células-Tronco Mesenquimais/metabolismo , Tecido AdiposoRESUMO
Introduction: The efficacy and safety of 3% diquafosol sodium eye drops in Chinese patients with dry eye in the real-world setting remains unclear. Methods: 3099 patients with dry eye symptoms were screened according to Asia Dry Eye Society latest recommendation. Among them, 3000 patients were enrolled for a phase IV study. We followed up with multiple clinical characteristics including corneal fluorescein staining, tear break up time, Schirmer's tests, visual acuity, intraocular pressure, and others. The follow ups were performed at baseline, 2 weeks and 4 weeks after treatment. Results: Based on the results of corneal fluorescein staining and tear break up time, all age and gender subgroups exhibited obvious alleviation of the symptoms among the patients with dry eye, and the data in elderly group showed the most significant alleviation. All the adverse drug reactions (ADRs, 6.17%) were recorded, among which 6% local ocular ADRs were included. Meanwhile, mild ADRs (91.8%) accounted for the most. Most of the ADRs (89.75%) got a quick and full recovery, with an average time at 15.6 days. 1.37% of patients dropped out of the study due to ADRs. Discussion: The use of 3% diquafosol sodium eye drop is effective and safe in the treatment of dry eye, with a low incidence of ADRs showing mild symptoms. This trial was registered at Chinese Clinical Trial Registry ID: ChiCTR1900021999 (Registration Date: 19/03/2019).
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Metal copper complexes have attracted extensive attention as potential alternatives to platinum-based anticancer drugs due to their possible different modes of action. Herein, a new copper(II) gluconate complex, namely [Cu(DPQ)(Gluc)]·2H2O (CuGluc, DPQ = pyrazino[2,3-f][1,10]phenanthroline), with good water-solubility and high anticancer activity was synthesized by using D-gluconic acid (Gluc-2H) as an auxiliary ligand. The complex was well characterized by single-crystal X-ray diffraction analysis, elemental analysis, molar conductivity, and Fourier transform infrared spectroscopy (FTIR). The DNA-binding experiments revealed that CuGluc was bound to DNA by intercalation with end-stacking binding. CuGluc could oxidatively cleave DNA, in which 1O2 and H2O2 were involved. In addition, CuGluc was bound to the IIA subdomain of human serum albumin (HSA) through hydrophobic interaction and hydrogen bonding, showing a good affinity for HSA. The complex showed superior anticancer activity toward several cancer cells than cisplatin in vitro. Further studies indicated that CuGluc caused apoptotic cell death in human liver cancer (HepG2) cells through elevated intracellular reactive oxygen species (ROS) levels, mitochondrial dysfunction, cell cycle arrest, and caspase activation. Interestingly, CuGluc also triggered the ferroptosis mechanism through lipid peroxide accumulation and inhibition of glutathione peroxidase 4 (GPX4) activity. More importantly, CuGluc significantly inhibited tumor growth in vivo, which may benefit from the combined effects of apoptosis and ferroptosis. This work provides a promising strategy to develop highly effective antitumor copper complexes by coordinating with the glucose metabolite D-gluconic acid and exploiting the synergistic effects of apoptosis and ferroptosis mechanisms.
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Antineoplásicos , Complexos de Coordenação , Ferroptose , Neoplasias , Humanos , Cobre/química , Peróxido de Hidrogênio/farmacologia , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Apoptose , Gluconatos/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Albumina Sérica Humana , DNA/química , Linhagem Celular TumoralRESUMO
Rapamycin is an immunosuppressive drug that is widely used in the postsurgery management of transplantation. To date, the mechanism by which rapamycin reduces posttransplant neovascularization has not been fully understood. Given the original avascularity and immune privilege of the cornea, corneal transplantation is considered as an ideal model to investigate neovascularization and its effects on allograft rejection. Previously, we found that myeloid-derived suppressor cells (MDSC) prolong corneal allograft survival through suppression of angiogenesis and lymphangiogenesis. Here, we show that depletion of MDSC abolished rapamycin-mediated suppression of neovascularization and elongation of corneal allograft survival. RNA-sequencing analysis revealed that rapamycin dramatically enhanced the expression of arginase 1 (Arg1). Furthermore, an Arg1 inhibitor also completely abolished the rapamycin-mediated beneficial effects after corneal transplantation. Taken together, these findings indicate that MDSC and elevated Arg1 activity are essential for the immunosuppressive and antiangiogenic functions of rapamycin.
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Transplante de Córnea , Células Supressoras Mieloides , Humanos , Sirolimo/farmacologia , Linfangiogênese , Rejeição de Enxerto , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Neovascularização PatológicaRESUMO
OBJECTIVE: This cross-sectional study aimed to reveal the association between ocular surface disorders and psychological, physiological situations among autoimmune rheumatic patients. METHODS: Ninety autoimmune rheumatic patients (180 eyes) hospitalized in the Department of Rheumatology, The Second Xiangya Hospital, Central South University and 30 controls (60 eyes) were enrolled in the study. All participants were assessed for ocular surface disorders including dry eye disease (DED) by the Ocular Surface Disease Index (OSDI) for symptoms evaluation, and slim lamp examinations for tear break-up time (TBUT), meibomian gland secretion, symblepharon and corneal clarity, Schirmer I test, corneal fluorescein staining (CFS), lid-parallel conjunctival folds (LIPCOF). Systematic conditions were evaluated using the Short Form 36-Health Survey (SF-36) for health-related quality of life, Hospital Anxiety and Depression Scale (HADS) for anxiety and depression, Health Assessment Questionnaire-Disability Index (HAQ-DI) for difficulties in activities of daily living, and Pittsburgh Sleep Quality Index (PSQI) for sleep quality. Pearson and spearman's analysis were conducted to examine the relationship between systematic conditions and ocular surface conditions. RESULTS: The analyses were controlled for age and sex. 52.22% of eyes (94 in 180) of autoimmune rheumatic patients and 21.67% of eyes (13 in 60) of controls were diagnosed with DED. The autoimmune rheumatic patients showed significant higher OSDI score, fewer basal tear secretion, more severe CFS and conjunctivochalasis than controls. There were no statistically significant differences in TBUT, meibomian gland secretion, symblepharon, and corneal clarity between the two groups. For systematic conditions, autoimmune rheumatic patients had significantly lower SF-36 scores, higher anxiety scores, and HAQ-DI scores than controls. No statistically significant differences were detected in depression scores and PSQI between the two groups. Among autoimmune rheumatic patients, OSDI scores were moderately correlated with quality of life, anxiety, depression and sleep quality. CONCLUSION: Factors including quality of life, anxiety, depression, and sleep quality are associated with ocular surface conditions, especially DED symptoms. Management of systemic conditions and psychotherapy should also be considered as part of the treatment among autoimmune rheumatic patients.
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Doenças da Túnica Conjuntiva , Síndromes do Olho Seco , Doenças Palpebrais , Doenças Reumáticas , Humanos , Qualidade de Vida , Estudos Transversais , Atividades Cotidianas , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/psicologia , Lágrimas/fisiologia , Doenças Palpebrais/complicações , Transtornos da Visão , Doenças Reumáticas/complicações , Glândulas TarsaisRESUMO
Copper complexes have long been considered as a promising class of anticancer or antibacterial therapeutics. In this paper, two novel copper(II) complexes containing a ß-carboline derivative and amino acids, namely [Cu(1-Im-ßc)(L-Val)]ClO4·0.5H2O (Cu1) and [Cu(1-Im-ßc)(L-Phe)]ClO4·0.5H2O (Cu2), where 1-Im-ßc = 1-(2-imidazolyl)-ß-carboline, L-Val = L-valine, and L-Phe = L-phenylalanine, were designed and synthesized. The complexes were characterized by elemental analysis, infrared spectroscopy, molar conductivity measurements, and mass spectrometry to determine their spatial structures and compositions. Both complexes bind to DNA by insertion. The complexes also show a good affinity for human serum albumin (HSA). In addition, the antitumor activity of the two complexes against lung cancer cells (A549), cervical cancer cells (HeLa), and breast cancer cells (MBA-MD-231) is significantly superior to that of the traditional antitumor drug, cisplatin. Finally, the anticancer mechanism results show that the complexes can induce apoptosis in HeLa cells, which is associated with mitochondrial damage, oxidative stress caused by reactive oxygen species (ROS) production, and activation of the caspase protein family. This study demonstrates that the introduction of aromatic heterocyclic alkaloid ligands with a broad spectrum of biological activities and water-soluble amino acid ligands into copper complexes can regulate their amphiphilic properties and biological activity, so as to obtain highly efficient copper-based therapeutics.
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Cobre , Humanos , Aminoácidos/química , Linhagem Celular Tumoral , Cobre/química , DNA/química , Lipídeos/química , Modelos Moleculares , Albumina Sérica Humana/química , Estrutura Terciária de Proteína , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologiaRESUMO
Background: The aim of this randomised prospective study is to compare the outcomes of traditional open trigger digit release versus ultrasound-guided modified small needle-knife (SNK) percutaneous release in the treatment of trigger digits. Methods: Patients with grade 2 and above trigger digits were enrolled into the study and randomly assigned to traditional open surgery (OS) or ultrasound-guided modified SNK percutaneous release group. The patients were followed up for 7, 30 and 180 days after treatment and data with regard to visual analogue scale (VAS) score and Quinnell grading (QG) was collected and compared between the two groups. Results: A total of 72 patients were enrolled in the study with 30 in the OS group and 42 in the SNK group. VAS scores and QG of the two groups significantly decreased at 7 days and 30 days after treatment compared to before treatment, but there was no significant difference between the two groups. There was also no differences between the two groups at 180 days and between the values at 30 days and 180 days. Conclusions: The outcomes of ultrasound-guided SNK percutaneous release is similar to traditional OS. Level of Evidence: Level II (Therapeutic).
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Dedo em Gatilho , Humanos , Dedo em Gatilho/diagnóstico por imagem , Dedo em Gatilho/cirurgia , Dedo em Gatilho/tratamento farmacológico , Estudos Prospectivos , Agulhas , Ultrassonografia , Ultrassonografia de IntervençãoRESUMO
PURPOSE: To assess the effectiveness and safety of continuous lavage with 1% voriconazole (CL) for moderate and severe fungal keratitis. METHODS: Thirty-one patients were randomized to receive topical eye drops either alone (T) or combined with continuous 1% voriconazole lavage (CL-T). The primary outcome was the cure rate at 3 months. The secondary outcomes were the 6-day efficacy, 3-day infiltration size and depth, hypopyon height, central corneal thickness (CCT), epithelial defect size, and subject feelings and clinical signs assessment scores. RESULTS: At 3 months, the cure rate was comparable between the groups in patients with moderate fungal keratitis (66.7% vs. 62.5%, P = 0.60). However, among severe cases, 4 cases (44.4%) in the CL-T group healed successfully, while none in the T group; this difference was not significant (P = 0.08), although it was very close to 0.05. This may be related to the small sample size. After 6 days, the percentage of patients with "worsened" ulcers in the CL-T group was lower than that in the T group (0% vs. 31%, P = 0.043). The infiltration size, infiltration depth, and hypopyon height in the CL-T group were smaller than those in the T group after 3 days (all P < 0.05). There was no difference in CCT, epithelial defect size, subject feelings scores, or clinical signs scores between groups. CONCLUSION: These outcomes suggest that CL is an effective and safe adjuvant method for controlling the progression of moderate and severe fungal keratitis. TRIAL REGISTRATION NUMBER: ChiCTR2100050565.
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Úlcera da Córnea , Infecções Oculares Fúngicas , Ceratite , Humanos , Voriconazol/uso terapêutico , Antifúngicos , Ceratite/diagnóstico , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Irrigação Terapêutica , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/microbiologia , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologiaRESUMO
PURPOSE: To describe a "magnetic conduction" technique for the removal of metallic intraocular foreign bodies (IOFBs) in the posterior segment combined with cataract extraction and pars plana vitrectomy and to report its outcomes. METHODS: We retrospectively analyzed the data of 42 eyes of 42 patients with posterior metallic IOFBs between April 2020 and February 2022. In all patients, cataract extraction was combined with pars plana vitrectomy. With an external magnet, the IOFBs were captured by a magnetized vitrectomy cutter, delivered to the anterior chamber, and then extracted through a corneal phacoemulsification incision. RESULTS: All patients were men, with a mean age of 45.6 ± 10.7 years. The mean size of the IOFBs was 3.5 ± 1.7 mm (range, 1.5-8.9 mm) in their longest dimension. A final best-corrected visual acuity of 20/200 or better was noted in 24 of 42 patients (57.1%). Postoperatively, recurrent retinal detachment was seen in three eyes. There were no other intraoperative or postoperative complications. CONCLUSION: The "magnetic conduction" technique combined with phacovitrectomy is a safe and feasible approach to removing IOFBs in the posterior segment.
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Catarata , Corpos Estranhos no Olho , Ferimentos Oculares Penetrantes , Facoemulsificação , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Ferimentos Oculares Penetrantes/cirurgia , Corpos Estranhos no Olho/complicações , Corpos Estranhos no Olho/diagnóstico , Corpos Estranhos no Olho/cirurgia , Vitrectomia/métodos , Complicações Pós-Operatórias/cirurgia , Fenômenos Magnéticos , Catarata/complicaçõesRESUMO
Herein, we report a four-step mechanism for the spontaneous multi-scale supramolecular assembly (MSSA) process in a two-phase system concerning an ionic liquid (IL). The complex ions, elementary building blocks (EBBs), [EBB]n clusters and macroscopic assembly (MA) sphere are formed step by step. The porous large-sized [EBB]n clusters in the glassy state can hardly stay in the IL phase and they transfer to the IL-water interface due to both electroneutrality and amphiphilicity. Then, the clusters undergo random collision in the interface driven by the Marangoni effect and capillary force thereafter. Finally, a single MA sphere can be formed owing to supramolecular interactions. To our knowledge, this is the first example realizing spontaneous whole-process supramolecular assembly covering microscopic, mesoscopic and macroscopic scales in extraction systems. The concept of multi-scale selectivity (MSS) is therefore suggested and its mechanism is revealed. The selective separation and solidification of metal ions can be realized in a MSSA-based extraction system depending on MSS. In addition, insights into the physicochemical characteristics of ILs from microscopic, mesoscopic to macroscopic scales are provided, and especially, the solvation effect of ILs on the large-sized clusters leading to the phase-splitting is examined. It is quite important that the polarization of uranyl in its complex, the growing of uranyl clusters in an IL as well as the glassy material of uranyl are investigated systematically on the basis of both experiment and theoretical calculations in this work.