Background CC-Cruiser is an artificial intelligence (AI) platform developed for diagnosing childhood cataracts and providing risk stratification and treatment recommendations. The high accuracy of CC-Cruiser was previously validated using specific datasets. The objective of this study was to compare the diagnostic efficacy and treatment decision-making capacity between CC-Cruiser and ophthalmologists in real-world clinical settings. Methods This multicentre randomized controlled trial was performed in five ophthalmic clinics in different areas across China. Pediatric patients (aged ≤ 14 years) without a definitive diagnosis of cataracts or history of previous eye surgery were randomized (1:1) to receive a diagnosis and treatment recommendation from either CC-Cruiser or senior consultants (with over 5 years of clinical experience in pediatric ophthalmology). The experts who provided a gold standard diagnosis, and the investigators who performed slit-lamp photography and data analysis were blinded to the group assignments. The primary outcome was the diagnostic performance for childhood cataracts with reference to cataract experts' standards. The secondary outcomes included the evaluation of disease severity and treatment determination, the time required for the diagnosis, and patient satisfaction, which was determined by the mean rating. This trial is registered with ClinicalTrials.gov ( NCT03240848 ). Findings Between August 9, 2017 and May 25, 2018, 350 participants (700 eyes) were randomly assigned for diagnosis by CC-Cruiser (350 eyes) or senior consultants (350 eyes). The accuracies of cataract diagnosis and treatment determination were 87.4% and 70.8%, respectively, for CC-Cruiser, which were significantly lower than 99.1% and 96.7%, respectively, for senior consultants ( p < 0.001, OR = 0.06 [95% CI 0.02 to 0.19]; and p < 0.001, OR = 0.08 [95% CI 0.03 to 0.25], respectively). The mean time for receiving a diagnosis from CC-Cruiser was 2.79 min, which was significantly less than 8.53 min for senior consultants ( p < 0.001, mean difference 5.74 [95% CI 5.43 to 6.05]). The patients were satisfied with the overall medical service quality provided by CC-Cruiser, typically with its time-saving feature in cataract diagnosis. Interpretation CC-Cruiser exhibited less accurate performance comparing to senior consultants in diagnosing childhood cataracts and making treatment decisions. However, the medical service provided by CC-Cruiser was less time-consuming and achieved a high level of patient satisfaction. CC-Cruiser has the capacity to assist human doctors in clinical practice in its current state. Funding National Key R&D Program of China (2018YFC0116500) and the Key Research Plan for the National Natural Science Foundation of China in Cultivation P...

Fibrosis is a chronic process involving development and progression of multiple diseases in various organs and is responsible for almost half of all known deaths. Epithelial–mesenchymal transition (EMT) is the vital process in organ fibrosis. Lens is an elegant biological tool to investigate the fibrosis process because of its unique biological properties. Using gain- and loss-of-function assays, and different lens fibrosis models, here we demonstrated that microRNA (miR)-26a and miR-26b, members of the miR-26 family have key roles in EMT and fibrosis. They can significantly inhibit proliferation, migration, EMT of lens epithelial cells and lens fibrosis in vitro and in vivo. Interestingly, we revealed that the mechanisms of anti-EMT effects of miR-26a and -26b are via directly targeting Jagged-1 and suppressing Jagged-1/Notch signaling. Furthermore, we provided in vitro and in vivo evidence that Jagged-1/Notch signaling is activated in TGFβ2-stimulated EMT, and blockade of Notch signaling can reverse lens epithelial cells (LECs) EMT and lens fibrosis. Given the general involvement of EMT in most fibrotic diseases, cancer metastasis and recurrence, miR-26 family and Notch pathway may have therapeutic uses in treating fibrotic diseases and cancers.

These data indicate that the altered tertiary and/or quaternary structures and the dominant negative effect of D140N mutant alphaB-crystallin underlie the molecular mechanism of cataractogenesis of this pedigree.

NF-κB is a family of important transcription factors involved in many cellular functions, such as cell survival, proliferation and stress responses. Many studies indicate that NF-κB is a stress sensitive transcription factor and its activation is regulated by reactive oxygen species. In previous studies, we and others demonstrated that this transcription factor can be activated by transient oxidative stress. However, the effects of sustained oxidative stress on NF-κB activation are not clear. The objective of this study is to determine the effects of sustained oxidative stress on NF-κB activation and to elucidate the signaling events affected by sustained oxidative stress. Human lens epithelial cells (HLEC) that were subjected to 4 h of continuous influx of hydrogen peroxide were used to investigate the effects of sustained oxidative stress on NF-κB activation. The data showed that, unlike transient oxidative stress, sustained exposure of HLEC to physiologically relevant levels of H 2 O 2 (50-100 μM for 4) did not induce the degradation of I-κB and activation of NF-κB, but attenuated TNFα-induced degradation of I-κB and activation of NF-κB. Sustained exposure of HLEC to these levels of H 2 O 2 also inactivated proteasome activity by 50-80%. Consistent with the role of the proteasome in degradation of I-κB and activation of NF-κB, treatment of HLEC with proteasome inhibitors also attenuated TNFα-induced I-κB degradation and NF-κB activation. The data also indicate that activation of NF-κB is essential for the cells to recover from oxidative stress. Inhibiting NF-κB activation during recovery from transient oxidative stress significantly reduced the cell viability. Together, these data indicate that sustained oxidative stress may inactivate the proteasome and subsequently inhibit NF-κB activation via impeding the degradation of I-κB. The oxidative inactivation of the proteasome and subsequent impairment of NF-κB activation may contribute to the death of lens epithelial cells, a common feature associated with cataract.