To evaluate the efficacy, complications, and clinical characteristics, including the ocular toxicity, of intravitreal melphalan(IVM) treatment for vitreous seeding in Chinese retinoblastoma patients. This was a retrospective, non-comparative analysis including 30 consecutive eyes of 23 patients with viable persistent or recurrent vitreous seeding following retinoblastoma treatment. All of the eyes received IVM injections (20–33 μg). Vitreous seeding control, determination of the ocular toxicity, and the clinical characteristics of intravitreal melphalan treatments were observed. The mean patient age at the time of the injection was 28 months (median = 22 months, range = 12–50 months). In total, 80 injections were administered in 30 eyes, the overall enucleation-free survival rate was 83.3% (25/30). The complications included retinal pigment epithelium (RPE) and choroidal atrophy (19/30, 63.3%), pupillary synechiae (13/30, 43.3%), iris atrophy (12/30, 40%), retinal vascular occlusion (12/30, 40.0%), optic atrophy (6/30, 20%), vitreous hemorrhage (3/30, 10%), persistent hypotonia and phthisis bulbi (4/30 13.3%), and cataracts (8/30, 26.6%). Twelve eyes demonstrated grade 3 or greater IVM-associated retinal or anterior segment toxicity post injection. Mean dosage given showed significant difference between the groups. There were no significant differences in the retinal toxicity grades regarding the seed classification or seed regression patterns. Intravitreal melphalan is an effective treatment for refractory vitreous seeding from retinoblastoma, but exhibits both anterior and posterior segment toxicity in Chinese patients.

Retinoblastoma protein (Rb) is a prototypical tumor suppressor that is vital to the negative regulation of the cell cycle and tumor progression. Hypo-phosphorylated Rb is associated with G0/G1 arrest by suppressing E2F transcription factor activity, whereas Rb hyper-phosphorylation allows E2F release and cell cycle progression from G0/G1 to S phase. However, the factors that regulate cyclin-dependent protein kinase (CDK)-dependent hyper-phosphorylation of Rb during the cell cycle remain obscure. In this study, we show that throughout the cell cycle, Rb is specifically small ubiquitin-like modifier (SUMO)ylated at early G1 phase. SUMOylation of Rb stimulates its phosphorylation level by recruiting a SUMO-interaction motif (SIM)-containing kinase CDK2, leading to Rb hyper-phosphorylation and E2F-1 release. In contrast, a SUMO-deficient Rb mutant results in reduced SUMOylation and phosphorylation, weakened CDK2 binding, and attenuated E2F-1 sequestration. Furthermore, we reveal that Rb SUMOylation is required for cell proliferation. Therefore, our study describes a novel mechanism that regulates Rb phosphorylation during cell cycle progression.

Osteoarthritis (OA) is a slow progressing degenerative disease that affects the joints, including the temporomandibular joint. In the present study, transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase 3 (MMP-3) in synovial fluid (SF) were examined in detecting cartilage synthesis and degradation in progression of temporomandibular joint osteoarthritis (TMJ OA) combined with disc displacement (DD) diseases. SF was obtained from 16 patients with TMJ OA combined with DD and 10 normal volunteers. TGF-β1 and MMP-3 levels were measured by enzyme-linked immunosorbent assay. In addition, TMJ OA combined with DD was classified into three stages based on radiographic signs on the preoperative tomograms and surgical findings at operation, and different treatment options were administered according to the stages. SF from TMJs with TMJ OA combined with DD showed higher levels of TGF-β1 and MMP-3 compared with the asymptomatic control TMJs. With the progression of TMJ OA combined with DD, TGF-β1 levels in SF were lower, while MMP-3 levels in SF were significantly higher. In conclusion, these data suggest that MMP-3 is not only involved in the pathological destruction process of TMJ OA combined with DD initially, but also has a positive correlation with the degree of pathological changes. Furthermore, a significant increase of TGF-β1 levels was found in the SF that were able to counteract the deleterious effects of MMP-3 at the early stage of TMJ OA combined DD, providing the scientific basis on repositioning displaced disc as early as possible for these patients.

Introduction: Artificial intelligence (AI) technology has made rapid progress for disease diagnosis and triage. In the field of ophthalmic diseases, image-based diagnosis has achieved high accuracy but still encounters limitations due to the lack of medical history. The emergence of ChatGPT enables human-computer interaction, allowing for the development of a multimodal AI system that integrates interactive text and image information.Objective: To develop a multimodal AI system using ChatGPT and anterior segment images for diagnosing and triaging ophthalmic diseases. To assess the AI system's performance through a two-stage cross-sectional study, starting with silent evaluation and followed by early clinical evaluation in outpatient clinics.Methods and analysis: Our study will be conducted across three distinct centers in Shanghai, Nanjing, and Suqian. The development of the smartphone-based multimodal AI system will take place in Shanghai with the goal of achieving ≥90% sensitivity and ≥95% specificity for diagnosing and triaging ophthalmic diseases. The first stage of the cross-sectional study will explore the system's performance in Shanghai's outpatient clinics. Medical histories will be collected without patient interaction, and anterior segment images will be captured using slit lamp equipment. This stage aims for ≥85% sensitivity and ≥95% specificity with a sample size of 100 patients. The second stage will take place at three locations, with Shanghai serving as the internal validation dataset, and Nanjing and Suqian as the external validation dataset. Medical history will be collected through patient interviews, and anterior segment images will be captured via smartphone devices. An expert panel will establish reference standards and assess AI accuracy for diagnosis and triage throughout all stages. A one-vs.-rest strategy will be used for data analysis, and a post-hoc power calculation will be performed to evaluate the impact of disease types on AI performance.Discussion: Our study may provide a user-friendly smartphone-based multimodal AI system for diagnosis and triage of ophthalmic diseases. This innovative system may support early detection of ocular abnormalities, facilitate establishment of a tiered healthcare system, and reduce the burdens on tertiary facilities.Trial registration: The study was registered in ClinicalTrials.gov on June 25th, 2023 (NCT 05930444).

Purpose: To summarize the clinicopathological characteristics and prognosis of uveal melanoma (UM) after enucleation in Chinese patients. Methods: Between 2003 and 2012, a series of 171 patients with UM received enucleation at the Eye & ENT Hospital of Fudan University in Shanghai. Patient clinical information was collected. Pathological examination and BAP1 staining of the enucleated eyes were conducted. Univariate and multivariate Cox proportional hazard regressions were conducted to determine the risk factors, and the survival rates were calculated and compared. Results: The study included 83 (49%) men and 88 (51%) women, with a mean age of 48.6 years. The mean largest basal tumor diameter and mean largest tumor thickness were 11.8 and 8.6 mm, respectively. Ciliary body involvement was observed in 19 tumors (11%). Spindle and nonspindle patterns were observed in 100 (58%) and 71 eyes (42%), respectively. Extrascleral extension was observed in three eyes (2%). BAP1 staining was negative in 34% (53/156) of all tumors and 53% (19/36) of the cases with melanoma-related metastasis. The mean follow-up period was 63.4 months for all patients with the exception of 11 patients, who were excluded because they were lost during follow-up. A large basal tumor diameter, ciliary body involvement, nonspindle cell type, extrascleral extension, and negative BAP1 staining were associated with a worse prognosis. The survival curves significantly differed between the BAP1-negative and BAP1-positive groups (P = 0.004). According to Kaplan–Meier analysis, the 5- and 10-year metastasis-free survival rates were 80% and 70%, respectively. Conclusions: A large basal tumor diameter, ciliary body involvement, nonspindle cell type, extrascleral extension, and negative BAP1 staining may be risk factors for the prediction of the UM prognosis. A younger age at diagnosis and a similar prognosis between genders may be unique features in Asian patients compared to the Caucasian population.