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BACKGROUND: Spheno-orbital meningioma (SOM) represents a unique variant of sphenoid wing meningiomas, distinguished by its propensity for bone infiltration and cranio-orbital involvement. SOM exhibits a considerable incidence of misdiagnosis and recurrence. PURPOSES: To elucidate the clinical, radiological, and pathological characteristics of SOM. METHODS: Review of electronic medical records, histopathology, radiological images and follow-up information of 100 SOM patients. RESULTS: Of the 100 patients (28 males, 72 females) with SOM, mean age was 46.8 ± 12.6 years and prevalent symptoms were proptosis (99%). All the CT scans showed hyperostosis with 89.3% of the hyperostosis having an irregular edge. In MRI scans, dural tail sign was observed across all patients and the cranio-orbital tumors often penetrated temporal muscle (74.1%), extraocular muscle (74.1%) and lacrimal gland (63%). All the 100 patients underwent surgical intervention, and among them, 62 individuals received postoperative radiotherapy. Grade I resections had a lower recurrence rate(16.7%), which further decreased with the addition of radiotherapy(13.9%). In contrast, all patients with grade II or higher grade resections without radiotherapy experienced recurrence, indicating a higher risk associated with less complete tumor removal. The pathological examination revealed that intraorbital sections exhibited comparable tumor density to intraorbital SOM tumors, along with increased fibrous density but decreased vascular distribution. CONCLUSIONS: Radiological characteristics of SOM included cranio-orbital tumors, hyperostosis of the sphenoid wing with an irregular edge, and dural tail sign. Combination of gross total resection and adjuvant radiotherapy was recommended to minimize recurrence rate. Intracranial SOM tumors tended to be softer and more bleed-prone than intraorbital sections, necessitating surgical precision.
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Imageamento por Ressonância Magnética , Neoplasias Meníngeas , Meningioma , Neoplasias Orbitárias , Osso Esfenoide , Tomografia Computadorizada por Raios X , Humanos , Meningioma/diagnóstico por imagem , Meningioma/patologia , Meningioma/diagnóstico , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Neoplasias Orbitárias/diagnóstico por imagem , Neoplasias Orbitárias/patologia , Neoplasias Orbitárias/diagnóstico , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/diagnóstico , Osso Esfenoide/patologia , Osso Esfenoide/diagnóstico por imagem , Estudos Retrospectivos , Idoso , Recidiva Local de Neoplasia , Seguimentos , Adulto JovemRESUMO
BACKGROUND: There are serious complications associated with hyaluronic acid (HA) facial injections, including vision impairment due to retinal artery ischemia. In this study, we put forth a clinically relevant model of retinal ischemia and reperfusion in rabbit. We used this to verify the efficacy of hyaluronidase intra-artery thrombolysis in the treatment of hyaluronic acid-induced retinal artery occlusion. METHODS: Retinal artery ischemia was induced by injecting HA into the ophthalmic artery (OA) of adult chinchilla rabbit, and reperfusion was achieved by intra-artery thrombolysis therapy with hyaluronidase following 60 min and 4 h of occlusion. Digital subtraction angiography (DSA) and fundus fluorescein angiography (FFA) were used to evaluate blood flow in the retina. Electroretinogram (ERG), hematoxylin and eosin staining and transmission electron microscope were used to evaluate the structure and function of the retina after ischemia and reperfusion following 60 min and 4 h of occlusion. RESULTS: DSA and FFA images confirmed occlusion of the ophthalmic and central retinal arteries, as well as reperfusion after hyaluronidase thrombolysis. ERG indicated retinal dysfunction following ischemia, and thrombolysis partially rescued its impairment following 4 h of occlusion. Hematoxylin and eosin staining and TUNEL staining revealed ischemia-induced histological damages in the retina at different time windows, and hyaluronidase thrombolysis partially mitigated these damages. CONCLUSIONS: We report a method to establish a HA-induced retinal artery occlusion animal model. Hyaluronidase intra-artery thrombolysis was used to recanalize the embolized OA at different time points. Using our method, we achieved retinal reperfusion, and an improvement was observed in the visual function of rabbits after hyaluronidase thrombolysis following 4 h of occlusion. We believe that hyaluronidase intra-artery thrombolysis is an effective method to treat HA-induced retinal artery occlusion in clinic. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Modelos Animais de Doenças , Ácido Hialurônico , Hialuronoglucosaminidase , Oclusão da Artéria Retiniana , Terapia Trombolítica , Animais , Coelhos , Oclusão da Artéria Retiniana/tratamento farmacológico , Oclusão da Artéria Retiniana/induzido quimicamente , Hialuronoglucosaminidase/uso terapêutico , Hialuronoglucosaminidase/administração & dosagem , Ácido Hialurônico/administração & dosagem , Terapia Trombolítica/métodos , Angiofluoresceinografia/métodos , Eletrorretinografia , Artéria Oftálmica , Angiografia Digital , MasculinoRESUMO
Despite decades of researches, the underlying mechanism of retinopathy of prematurity (ROP) remains unclear. The role of Sirt2, which is involved in both angiogenesis and inflammation, both pivotal in ROP, was investigated in an animal model of ROP known as oxygen-induced retinopathy (OIR). Our study found that Sirt2 was overexpressed and colocalized with microglia in OIR. Furthermore, it demonstrated that the level of Sirt2 was upregulated in hypoxia microglia BV-2 in vitro. Subsequently, our results elucidated that administration of the Sirt2 antagonist AGK2 attenuated the avascular and neovascular area and downregulated the expression of IGF-1. The phosphorylation of Akt and the expression of IGF-1 were upregulated in hypoxia BV-2 and conditional media collected from BV-2 under hypoxia promoted the migration and tube formation of retinal capillary endothelial cells, which were suppressed with AGK2. Notably, our findings are the first to demonstrate the deleterious role of Sirt2 in ROP, as Sirt2 inhibition led to the downregulation of Akt/IGF-1 and ameliorated vasculopathy, ultimately improving visual function. These results suggest that Sirt2 may be a promising therapeutic target for ROP.
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Neovascularização Retiniana , Retinopatia da Prematuridade , Animais , Humanos , Recém-Nascido , Camundongos , Retinopatia da Prematuridade/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Crescimento Insulin-Like I/efeitos adversos , Fator de Crescimento Insulin-Like I/metabolismo , Células Endoteliais/metabolismo , Sirtuína 2/genética , Neovascularização Retiniana/metabolismo , Oxigênio/toxicidade , Hipóxia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Animais Recém-NascidosRESUMO
For bismuth layered structural ferroelectrics (BLSFs), CaBi2Ta2O9 (CBTa) demonstrates valuable application potential for a high Curie temperature (TC) of 923 °C and a good high-temperature resistivity, but low piezoelectric constant d33 values. Compared with CBTa-based ceramics, CaBi2Nb2O9 (CBN) with a high TC of 940 °C is easy to modify and realize excellent enhancement of piezoelectric properties. Here, by introducing a CBN-based component into CBTa, a new type of solid-solution ceramic with the formula Ca0.94(LiCe)0.03Bi2Ta2O9-xCa0.94(LiCe)0.03Bi2Nb2O9 (LC-CBTa-xCBN) is fabricated to obtain the advantages of both of them. Moreover, optimal electrical performances are obtained in the LC-CBTa-0.4CBN ceramic (d33 â¼ 14.1 pC/N, ρ â¼ 1.08 × 106 at 600 °C, TC â¼ 940 °C). The correlated characterizations, including structure and electricity, provide further realization of an enhanced performance mechanism. Therefore, this method of constructing a new type of solid solution provides a new strategy to modify BLSFs.
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A 33-year-old lady was referred to our clinic with a history of left upper eyelid swelling and difficulty to open her left eye for more than 4 years. Her globe was in infero-nasal displacement, and ocular movement was not full, with restriction to every direction. No clinical sign including eye redness, pain or visual loss was found on examination. Exophthalmometry confirmed 2 mm of left-sided proptosis. Computed tomography (CT) imaging of the orbit obtained in axial and coronal planes depicted an irregular and heterogeneous soft-tissue density mass in the left lacrimal gland, measuring 25 × 17 mm. Magnetic resonance imaging (MRI) revealed the mass of slightly longer T1 and slightly longer/shorter T2 signal, and Gd-enhanced MRI showed a significant enhancement. The tumor was first presumably diagnosed of pleomorphic adenomas. A surgery was applied to remove the tumor completely. Histopathological evaluation led to the diagnosis of PEComa.
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PURPOSE: This study attempted to estimate the impact of eye-preserving therapies for the long-term prognosis of patients with advanced retinoblastoma with regard to overall survival and ocular salvage. DESIGN: Retrospective cohort study covering all 31 provinces (38 retinoblastoma treating centers) of mainland China. PARTICIPANTS: One thousand six hundred seventy-eight patients diagnosed with group D or E retinoblastoma from January 2006 through May 2016. METHODS: Chart review was performed. The patients were divided into primary enucleation and eye-preserving groups, and they were followed up for survival status. The impact of initial treatment on survival was evaluated by Cox analyses. MAIN OUTCOME MEASURES: Overall survival and final eye preservation. RESULTS: After a median follow-up of 43.9 months, 196 patients (12%) died, and the 5-year overall survival was 86%. In total, the eyeball preservation rate was 48%. In this cohort, 1172 patients (70%) had unilateral retinoblastoma, whereas 506 patients (30%) had bilateral disease. For patients with unilateral disease, 570 eyes (49%) underwent primary enucleation, and 602 patients (51%) received eye-preserving therapies initially. During the follow-up (median, 45.6 months), 59 patients (10%) from the primary enucleation group and 56 patients (9.3%) from the eye-preserving group died. Multivariate Cox analyses indicated no significant difference in overall survival between the 2 groups (hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.85-1.84; P = 0.250). For patients with bilateral disease, 95 eyes (19%) underwent primary enucleation, and 411 patients (81%) received eye-preserving therapies initially. During the follow-up (median, 40.1 months), 12 patients (13%) from the primary enucleation group and 69 patients (17%) from the eye-preserving group died. For bilateral retinoblastoma with the worse eye classified as group E, patients undergoing primary enucleation exhibited better overall survival (HR, 2.35; 95% CI, 1.10-5.01; P = 0.027); however, this survival advantage was not evident until passing 22.6 months after initial diagnosis. CONCLUSIONS: Eye-preserving therapies have been used widely for advanced retinoblastoma in China. Patients with bilateral disease whose worse eye was classified as group E and who initially underwent eye-preserving therapies exhibited a worse overall survival. The choice of primary treatment for advanced retinoblastoma should be weighed carefully.
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Neoplasias da Retina/terapia , Retinoblastoma/terapia , Terapia de Salvação , Antineoplásicos/uso terapêutico , Braquiterapia , Pré-Escolar , China , Terapia Combinada , Crioterapia , Enucleação Ocular , Feminino , Seguimentos , Humanos , Lactente , Fotocoagulação a Laser , Masculino , Neoplasias da Retina/mortalidade , Neoplasias da Retina/patologia , Retinoblastoma/mortalidade , Retinoblastoma/patologia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND Lacrimal gland pleomorphic adenoma (LGPA) is the most common clinically benign epithelial tumor of the lacrimal gland and is predominantly comprised of epithelial cells and interstitial components. At present, the exact pathogenesis of LGPA remains unclear. Previous research has indicated that the occurrence of LGPA may be related to excessive cell proliferation. MATERIAL AND METHODS This study observed the clinicopathological characteristics of LGPA and investigated the tumorigenesis mechanism of cell over-proliferation caused by the imbalance between apoptosis and proliferation. A total of 27 cases were collected from the Department of Ophthalmology of the Affiliated Hospital of Chengde Medical University and the Third Medical Center of Chinese PLA General Hospital from April 2017 to November 2019. Hematoxylin-eosin (HE) staining and immunohistochemical staining were used to observe the pathological characteristics and analyze the expression of bcl-2 and bax in the lacrimal gland. RESULTS Compared with normal lacrimal gland tissues, LGPA tumor tissues had obvious changes in pathological morphology. The expression of bcl-2 in LGPA lesion tissues was dramatically higher (P<0.001), the expression of bax was not significantly different between groups (P=0.25), but the ratio of bcl-2/bax was significantly higher in tumor tissues (P=0.01). CONCLUSIONS We found that the lacrimal gland tumor tissues had obvious excessive proliferation in pathomorphology, which revealed the necessity of complete surgical removal of the capsule from the perspective of pathological morphology and provided a theoretical basis for the hypothesis that the imbalance between apoptosis and proliferation could lead to cell hyperproliferation.
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Adenoma Pleomorfo/metabolismo , Adenoma Pleomorfo/patologia , Aparelho Lacrimal/patologia , Adulto , Apoptose/fisiologia , Carcinogênese/metabolismo , Proliferação de Células/fisiologia , Transformação Celular Neoplásica/patologia , Neoplasias Oculares/patologia , Neoplasias Oculares/cirurgia , Feminino , Humanos , Doenças do Aparelho Lacrimal/patologia , Doenças do Aparelho Lacrimal/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/patologia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Proteína X Associada a bcl-2/análiseRESUMO
RATIONALE: Discriminating between aglycone-substituted and saccharide-substituted saikosaponins by liquid chromatography/tandem mass spectrometry (LC/MSn ) is a long-standing issue that is still to be resolved. It is necessary to characterize the two types of substituted saikosaponins taking into consideration the potential significant difference in their bioactivity. METHODS: Taking the substituents malonyl and acetyl as examples, we developed a MS strategy to discriminate between the aglycone-substituted and saccharide-substituted saikosaponins through comparing their Y0 - nH2 O (n = 1-2) ions from the protonated molecules in the full-scan mass spectra and their B ions in the MS2 spectra of sodium-adduct molecules in the positive mode. RESULTS: The deprotonated molecules of the aglycone-substituted saikosaponins presented similar fragmentation patterns to those of saccharide-substituted ones in the negative mode, which could not discriminate whether the substitutes were located on the aglycone or the saccharide. In contrast, the Y0 - nH2 O (n = 1-2) ions containing or no substituent were observed respectively in the mass fragmentation of the protonated molecules of aglycone-substituted or saccharide-substituted saikosaponins in the positive mode. In addition, the B ions containing or no substituent were observed respectively in the mass fragmentation of the sodium-adduct molecules of the saccharide-substituted or aglycone-substituted saikosaponins in the positive mode. Two aglycone-malonylated saikosaponins were reported for the first time. CONCLUSIONS: Whether the substituents were located on the aglycone or the saccharide could be determined according to the Y0 - nH2 O (n = 1-2) ions from the protonated molecules in the full-scan mass spectra and the B ions in the MS2 spectra of sodium-adduct molecules in the positive mode. Our results have updated the mass fragmentation patterns of substituted saikosaponins, which is helpful for the quality control of pharmaceutical preparations containing saikosaponins. More importantly, this MS strategy should be able to be extended to characterize other substituted saponins of bioactive significance in future studies.
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OBJECTIVE: To analyze the reasons of orbital exenteration for orbital retinoblastoma (RB) patients. METHODS: Retrospective case series study. Clinical records were reviewed retrospectively of 17 orbital RB patients who had undergone exenteration from November 1999 to November 2010 at Armed Police General Hospital. The clinical records included ophthalmic history, process of diagnosis and treatment, symptom and signs, surgical approach, pathological diagnosis and follow-up results. The reasons of orbital exenteration for orbital RB patients according to medical history, process of diagnosis and treatment were analyzed. RESULTS: The average age of patient was 3.2 years old. The ratio of male versus female was 1.1: 1. The common clinical findings were as following: 11 cases of orbital mass, 7 cases of exophthalmos, 6 cases with palpebral edema, 4 cases of conjunctival congestion and edema with conjunctival mass, and 2 cases with orbital pain. Reasons for orbital exenteration were as following: 7 patients who lost the opportunity of the treatment because of concernning about the cost of treatment and poor prognosis and caused worst outcome. Exenteration had to be done eventually. Five cases of orbital recurrence happened after enucleation. Three patients' Rb invaded into orbit after conservative treatment intravenous chemotherapy or radio therapy alone. Two cases were misdiagnosed and mishandled causing rapidly tumor spread into the orbit. CONCLUSIONS: The major reasons of orbital exenteration for orbital RB patients lies in the following: giving up treatment from patients, tumor recurrence in the orbit after enucleation, progressing of orbital RB after simple conservative treatment, misdiagnosis and mishandling to let RB invade into orbit rapidly.
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Neoplasias da Retina/cirurgia , Retinoblastoma/cirurgia , Pré-Escolar , Erros de Diagnóstico , Feminino , Humanos , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia , Órbita , Exenteração Orbitária , Neoplasias da Retina/complicações , Neoplasias da Retina/diagnóstico , Retinoblastoma/complicações , Retinoblastoma/diagnóstico , Estudos RetrospectivosRESUMO
Purpose: We describe a case of fat-forming solitary fibrous tumor (SFT) of the orbit with typical findings on imaging that may improve the awareness of orbital fat-forming SFT. Observations: An 88-year-old female presented with exophthalmos and pain in her right eye. Preoperative imaging showed an oval, well-defined mass with soft-tissue density, interspersed with a well-circumscribed lesion. The lesion showed low-density in computed tomography (CT) scans, hyperintense in T1/T2 weighted images of magnetic resonance imaging (MRI) scans and hypointense in fat-suppressed images of MRI scans. The tumor was removed en bloc and diagnosed as low-grade malignant fat-forming SFT by pathological examination. There was no evidence of recurrence 9-month postoperatively. Conclusions: The imaging feature of orbital fat-forming SFT is a well-defined solid tumor interspersed with adipose tissue. Such findings are vital for the preoperative diagnosis and the choice of the treatment.
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The demand for ultra-high-temperature piezoelectric sensors in industrial applications has witnessed a rapid upsurge. In this study, the piezoelectric properties of La2Ti2O7 (LTO) piezoelectric ceramics with a perovskite-like layered structure were enhanced by doping with Li/Ce ions. It was found that a remarkable 300% enhancement in the piezoelectric constant (d33) value was achieved in Li/Ce-doped LTO ceramics compared to their pristine counterparts, reaching 6.4 pC N-1 at room temperature with an ultra-high Curie temperature of 1408 °C. After annealing at 500 °C, the d33 value of the samples can be further improved to 7.4 pC N-1. Moreover, temperature-dependent resistivity measurements indicate that even at 1000 °C, the ceramics exhibit a high resistivity of 8.9 × 105 Ω cm. By combining X-ray diffraction, Raman spectra, transmission electron microscopy and piezoresponse force microscopy data, the enhanced piezoelectricity of the ceramics is attributed to local heterogeneity induced by Li/Ce doping. Our results unequivocally demonstrate the suitability of modified LTO ceramics for ultra-high-temperature piezoelectric applications.
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PURPOSE: To clarify the clinical, diagnostic, and treatment characteristics of orbital liposarcoma. DESIGN: Retrospective observational case series. METHODS: A review was performed of electronic medical records, histopathology, radiological images, and follow-up information for 21 patients with orbital liposarcoma. RESULTS: The predominant clinical manifestation of this disease was painless exophthalmos. The most frequently encountered pathological types were well-differentiated and myxoid liposarcoma. Preoperative radiological images from 15 patients showed that orbital liposarcoma initially developed in extraocular muscle in 9 patients. Furthermore, all well-differentiated liposarcomas exhibited the radiographic characteristics of irregular and ill-defined adipose tissue, whereas only 12.5% of myxoid liposarcomas had the imaging characteristics. For the patients who exclusively underwent surgery, all of those with subtotal excisions experienced recurrence, 63.6% of marginal excisions recurred, and 50% of wide excisions resulted in recurrence. However, none of the patients who underwent marginal excisions or wide excisions combined with adjuvant radiotherapy exhibited recurrence. The analysis of magnetic resonance imaging findings in 3 patients who underwent neoadjuvant radiotherapy revealed that the tumor size remained stable in a patient with well-differentiated liposarcoma, whereas another patient with the same type of tumor exhibited a gradual increase in size. Conversely, a patient with myxoid liposarcoma experienced a significant reduction in tumor size following neoadjuvant radiotherapy. CONCLUSION: Orbital liposarcoma demonstrated a propensity for developing in the extraocular muscle. The radiological images of orbital well-differentiated liposarcomas were characterized by irregular and ill-defined adipose tissue. Surgery combined with radiotherapy demonstrated potential in reducing recurrence rates. Notably, orbital myxoid liposarcoma exhibited greater sensitivity to radiotherapy compared to well-differentiated liposarcoma.
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Lipossarcoma , Imageamento por Ressonância Magnética , Neoplasias Orbitárias , Humanos , Estudos Retrospectivos , Neoplasias Orbitárias/diagnóstico , Neoplasias Orbitárias/cirurgia , Neoplasias Orbitárias/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Lipossarcoma/diagnóstico , Lipossarcoma/cirurgia , Lipossarcoma/terapia , Tomografia Computadorizada por Raios X , Procedimentos Cirúrgicos Oftalmológicos , Recidiva Local de Neoplasia , Idoso de 80 Anos ou mais , Seguimentos , Exoftalmia/diagnóstico , Músculos Oculomotores/cirurgia , Músculos Oculomotores/patologia , Músculos Oculomotores/diagnóstico por imagem , Radioterapia AdjuvanteRESUMO
Introduction: Lacrimal gland adenoid cystic carcinoma (LGACC) is characterized by a high rate of recurrence, perineural invasion, and propensity for distant metastasis, resulting in poor prognosis. This case report aimed to highlight the diagnostic and therapeutic challenges of LGACC, underscore the importance of resectioning the tumor as completely as possible for the first time, adhere to postoperative adjuvant therapy, and provide detailed insights into its surgical and diagnostic management that may not be extensively covered in large case series and meta-analyses. Case presentation: A 34-year-old man presented with progressive left eye proptosis for 4 months. Initial evaluation and imaging led to a high suspicion of LGACC, which was confirmed after an eye-sparing excision of the left orbital tumor. The patient declined to undergo postoperative radiotherapy, which was recommended after the surgery. Thus, despite surgical intervention, the patient experienced tumor recurrence 3 months post-surgery, leading to orbital exenteration. Pathological examination confirmed the presence of poorly differentiated LGACC.This time the patient underwent postoperative radiotherapy, as recommended. However, despite local control, the patient developed an intracranial metastasis within a year. Conclusion: LGACC presents significant diagnostic and therapeutic challenges owing to its insidious onset, lack of specific symptoms, and high potential for recurrence and metastasis. Thus, this case emphasizes the need for early diagnosis, aggressive treatment, and adherence to postoperative adjuvant therapy to improve patient outcomes. Future research should focus on understanding the pathogenesis of LGACC and on developing standardized diagnostic and treatment protocols to enhance patient prognosis and survival.
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BACKGROUND: Super-selected intra-arterial chemotherapy has increasingly been used as conservative management for retinoblastoma during the past decade. However, the absence of evidence from randomised controlled trials engendered controversy in the administration route of chemotherapy. We aimed to assess the efficacy and safety of intra-arterial chemotherapy compared with intravenous chemotherapy. METHODS: This open-label, multicentre, randomised trial was done at six hospitals in China. Patients with new-onset unilateral group D or E retinoblastoma (poorly defined, large, or very large tumours, according to the International Intraocular Retinoblastoma Classification) without high-risk clinical factors were included. Patients were randomly assigned (1:1) to receive intra-arterial chemotherapy (injections of 0·5 mg/kg [or depending on age] melphalan with 20 mg carboplatin [first and third cycles] or with 1 mg topotecan [second and fourth cycles]) or intravenous chemotherapy (0·05 mg/kg [or 1·5 mg/m2] vincristine, 5 mg/kg [or 150 mg/m2] etoposide, and 18·6 mg/kg [or 560 mg/m2] carboplatin for six cycles). After intra-arterial chemotherapy, patients received a subcutaneous injection of 0·1 mL nadroparin calcium twice at a 12 h interval. Both intra-arterial and intravenous chemotherapy cycles were completed every 4 weeks. No masking was done, except of independent statisticians, who were masked to the allocation information. The primary outcome was 2-year progression-free globe salvage rate, defined as the time from randomisation to tumour progression or enucleation, whichever occurred first, and was analysed by intention to treat. We also recorded predefined safety outcomes (myelosuppression and ophthalmic arterial stenosis or occlusion) and severe adverse events likely to be related to study treatment. The study is registered with the Chinese Clinical Trial Registry, ChiCTR-IPR-15006469, and is complete. FINDINGS: Between June 1, 2015, and June 1, 2018, 234 patients with newly diagnosed retinoblastoma were screened and 143 eligible patients (median age 23·6 months [IQR 14·0-31·9]) were enrolled and randomly assigned to the intra-arterial chemotherapy group (n=72) or the intravenous chemotherapy group (n=71). At a median follow-up of 35·8 months (IQR 28·4-43·0), the 2-year progression-free globe salvage rate was 53% (38 of 72 patients) in the intra-arterial chemotherapy group and 27% (19 of 71 patients) in the intravenous chemotherapy group (risk ratio 1·97, 95% CI 1·27-3·07, p=0·0020). Myelosuppression was less common in the intra-arterial chemotherapy group than in the intravenous chemotherapy group (37 [51%] of 72 patients vs 50 [70%] of 71 patients; 0·73, 95% CI 0·56-0·96, p=0·021) and less severe (ptrend=0·0070). In the intra-arterial chemotherapy group, two (3%) of 72 patients had ophthalmic artery occlusion and 13 (18%) patients had ophthalmic artery stenosis. INTERPRETATION: Our findings show that intra-arterial chemotherapy could significantly improve the globe salvage rate in children with advanced unilateral retinoblastoma compared with intravenous chemotherapy, with mild systemic complications and no difference in overall survival rate. Intra-arterial chemotherapy could be an acceptable first-line treatment in children with advanced unilateral retinoblastoma. FUNDING: Scientific Research Program of the National Health and Family Planning Commission of China, the Clinical Research Plan of Shanghai Hospital Development Center, the National Natural Science Foundation of China, and the Science and Technology Commission of Shanghai Municipality.
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Neoplasias da Retina , Retinoblastoma , Humanos , Criança , Lactente , Pré-Escolar , Retinoblastoma/tratamento farmacológico , Retinoblastoma/induzido quimicamente , Carboplatina/efeitos adversos , Constrição Patológica/induzido quimicamente , China , Neoplasias da Retina/tratamento farmacológico , Neoplasias da Retina/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: The purpose of this study was to show the clinical and imaging characteristics in patients with congenital orbital fibrosis. METHODS: A retrospective review of a series of 14 patients with congenital orbital fibrosis hospitalized in Institute of Orbital Disease during 2005 to 2009 have been characterized. Patients aged from 3 months to 18 years old, the median age was 7 years old, 6 cases (43%) were male. RESULTS: Ocular changes were found at birth in all patients, symptoms at onset of the disease included dysfunction of eye movement (12 cases), lagophthalmos (7 cases), diplopia (5 cases), exophthalmos (4 cases), conjunctival congestion (4 cases) and endophthalmos (2 cases). The results of medical examinations including visual acuity, exophthalmos or endophthalmos, diplopia with or without compensative head station, displacement of the eye, lagophthalmos, blephroptosis and ocular dyskinesia all have been record. In the 14 cases, 13 patients have undertaken the CT imaging examination, soft tissue lesions have been found in the orbit with high density and irregular shape, accompanied with thickened ocular muscles and anatomical changes. Of the 9 cases which underwent MRI examination, all of the lesions showed medium signals in T(1)WI, with medium to low signals in T(2)WI. Local excision has been performed in 2 patients, we found that the orbital lesions packaged with hard fibrous tissues around, and the ocular muscles were thick and stark. Pathological examination showed fibrosis and degeneration in the lesions, lacrimal gland and ocular muscles. Some lymphocyte infiltration also has been observed. CONCLUSIONS: Congenital orbital fibrosis is an orbital disease occurs at birth and is characterized with series of signs such as endophthalmos or exophthalmos, ocular dyskinesia and diplopia. Imaging examinations often find abnormal mass with irregular shape and soft tissue density in orbit. Till now, no efficient therapy has been established.
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Órbita , Doenças Orbitárias/congênito , Doenças Orbitárias/diagnóstico , Adolescente , Criança , Pré-Escolar , Exoftalmia , Movimentos Oculares , Feminino , Fibrose , Humanos , Lactente , Masculino , Órbita/patologia , Doenças Orbitárias/patologia , Estudos RetrospectivosRESUMO
The incorporation of functional groups endows graphene oxide (GO) with different surface charges, which plays important roles in biological interactions with cells. However, the effect of surface charge of GO derivatives on ocular biocompatibility has not been fully elucidated. Previously, we found that positively, negatively and neutrally charged PEGylated GO (PEG-GO) nanosheets exerted similar effect on the viability of ocular cells. In this work, we performed in vitro and in vivo studies to comprehensively study the effect of surface charge of PEG-GO on ocular compatibility. The in vitro results showed that the cellular uptake efficacy of negatively charged PEG-GO nanosheets was significantly decreased compared with positively charged and neutrally charged analogs. However, three kinds of PEG-GO nanosheets produced similar amounts of intracellular reactive oxygen species and showed similar influence on mitochondrial membrane potential. By analysis of global gene expression profiles, we found that the correlation coefficients between three kinds of PEG-GO-treated cells were more than 0.98. Furthermore, in vivo results showed that all these PEG-GO nanosheets had no significant toxicity to ocular structure and function. Taken together, our work suggested that surface charge of PEG-GO exerted negligible effect on its ocular compatibility, except for the cellular uptake. Our work is conducive to understanding the relationship between surface charge and biocompatibility of GO derivatives.
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Graphene oxide (GO) has several potential biomedical applications and therefore cytotoxic evaluation of GO is very important. However, the two most common in vitro models for testing cytotoxicity-primary human cells and immortalized cell lines-suffer serious limitations, namely limited supplies of cells and unrealistic cellular responses, respectively. Here, we demonstrate the use of embryonic stem cell (ESC)-derived cells to study GO cytotoxicity. We tested the use of retinal pigment epithelium (RPE) cells derived from three-dimensional human ESC cultures ("ESC-RPE" cells) as a model of GO cytotoxicity by exposing them to varying concentrations of GO nanosheets. For comparison, we also performed the same test with primary human retinal pigment epithelium cells ("hRPE"), and with cells derived from a human RPE cell line ("ARPE19" cells). We found that cytotoxicity metrics (viability, apoptosis, intracellular reactive oxygen species, and mitochondrial membrane potential) were very similar in ESC-RPE cells and hRPE cells, and those in ARPE19 cells were very different. We conclude that cell models of GO cytotoxicity derived from ESCs are an excellent alternative to primary human cells, without the limitations of tissue availability.
Assuntos
Grafite/toxicidade , Células-Tronco Embrionárias Humanas/citologia , Nanoestruturas/toxicidade , Epitélio Pigmentado da Retina/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular , Células-Tronco Embrionárias Humanas/efeitos dos fármacos , Células-Tronco Embrionárias Humanas/metabolismo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/metabolismo , Testes de ToxicidadeRESUMO
OBJECTIVE: To study the cell membrane of T-lymphocytes in thyroid associated ophthalmopathy (TAO) by using atomic force microscopy (AFM). METHODS: Case-control study. Forty-two patients were selected as the subjects, and divided into two groups: acute stage (18) and stationary stage (24) ones on the basis of symptom. Ninety-two healthy persons were in the normal groups. Dynal immunomagnetic beads isolation method was used to separate the T cells. CD3+ was chosen as a surface molecule marker of T cells to determine the purity of cells isolated. Cultivated T cells were observed by AFM. Amplitude and height images were obtained in the tapping mode with a scan rate of 2 Hz and an integral gain of 0.3 to 0.5. Statistical analysis was performed using single-factor analysis of variance and the P value was calculated. RESULTS: The topographies of these three groups of T cells showed significant difference (F = 28.809, 58.213, 169.789, 35.933, 121.325; P < 0.05. Average diameter and roughness of T cells in acute stage of TAO were significantly greater than those of the other two groups. One way analysis of variance showed that significant differences in various parameters (Ra, Peak count, Rpm, Rvm, Surface area diff) were found between these three groups (P = 0.047, 0.002). CONCLUSIONS: The morphology and ultrastructure of lymphocytes in TAO are different from the normal subjects by observation with AFM. Lymphocytes in acute stage of TAO are also different from those in stationary stage.