Chongyi Li

This study aimed to systematically study the characterize of retinal damage induced by 525 nm laser irradiation at different power densities through multimodal assessment methods, including structural, functional and cytokine analyses. A total of 24 rabbits were exposed to laser irradiation at 0.5, 200, 500, and 1000 mW/cm² with a single-eye exposure duration of 0.25 s. Multimodal evaluations including ERG, OCT/OCTA, histopathology and aqueous humor cytokine microarray analysis were used to evaluate the characteristics of laser-induced injury in rabbit eyes. No visible functional or pathological damage was observed after low-power laser radiation (0.5 mW/cm²). Laser irradiation exceeding 200 mW/cm² induced transient electroretinographic suppression and persistent laser spots in the fundus. Laser-induced retinal edema and hemorrhage were naturally absorbed within 7 days after injury, and cellular damage and structural changes persisted in the form of old plaques (14d). Notably, 1000 mW/cm² laser exposure caused severe retinal detachment (1d), ultimately leading to a retinal hole (14d). There was no significant difference in the inflammatory array clustering analysis of anterior aqueous humor, but several individual cytokines showed statistically significant differences: ANG-1 was upregulated (500 and 1000 mW/cm², p < 0.01) while VEGF-A was downregulated (500 mW/cm², p < 0.05); MIP-1β was significantly increased (200 mW/cm², p < 0.05), whereas IL-1RA was decreased (500 mW/cm², p < 0.05). The 525 nm laser induced dose-dependent retinal injury, ranging from reversible functional inhibition to irreversible structural damage, and triggered the expression of cytokines related to vascular stability and inflammation regulation.

Radiation-induced cataracts (RIC), a significant cause of blindness, arise from oxidative damage and inflammation in the lens epithelium, and there has been a lack of effective targeted therapeutic drugs in clinic. Here, we proposed and developed a novel approach for prevention and treatment of RIC via multifunctional nanozymes. We first demonstrated activation of the cGAS-STING pathway can drive mitochondrial oxidative stress and cytosolic double-stranded DNA (dsDNA) accumulation in ionizing radiation (IR)-exposed lens epithelial cells (LECs). Accordingly, a nanozyme-based drug delivery system, namely porous CeO₂ loaded with STING inhibitors H-151 (CeO₂@H-151), was developed for RIC prevention and treatment. Importantly, CeO₂@H-151 nanozymes not only decreased reactive oxygen species (ROS) production induced by mitochondrial oxidative injury, but also reduced inflammation caused by increased dsDNA. This can be attributed to the synergistic effect of antioxidant, anti-inflammation and protein homeostasis-preserving of CeO₂@H-151 nanozymes. It also revealed CeO₂@H-151 nanozymes exerted protein homeostasis preservation through H-151 bound to the Cys172 oxidative modification site of PRDX2. This work provides a synergistic nanotherapeutic strategy targeting the cGAS-STING pathway, offering a promising approach for preventing and treating RIC and even other oxidative-inflammatory disorders. Graphical Abstract

AIM: To investigate the incidence of dry eye disease (DED) and relevant risk factors among patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. METHODS: This cross-sectional, observational analysis included 993 patients with corona virus disease 2019 (COVID-19) treated at the National Exhibition and Convention Center (Shanghai) Fangcang Shelter Hospital, from April 10 to May 26, 2022. Totally 944 uninfected control participants were recruited. All participants completed ocular surface disease index (OSDI) questionnaires, and DED symptoms were determined using OSDI scores. The demographic characteristics, length of hospital stay and in nasopharyngeal swabs were performed using questionnaires. SARS-CoV-2 Omicron variant infection was confirmed by nucleic acid-based detection in nasopharyngeal swabs using a 2019-nCoV nucleic acid detection kit. The risk factors for DED symptoms among patients with COVID-19 and control participants were determined by logistic regression analysis. RESULTS: Patients with COVID-19 showed a higher incidence of DED than controls (64.9% vs 55.1%, P<0.001). SARS-CoV- 2 infection [odds ratios (ORs) (95%CI): 1.271 (1.038, 1.556)], use of contact lenses [ORs (95%CI): 9.350 (3.676, 23.783)], history of corneal refractive surgery [ORs (95%CI): 2.047 (1.494, 2.804)], poor sleep quality [ORs (95%CI): 2.657 (2.029, 3.480)], and video display terminal (VDT) use for more than 8h per day [ORs (95%CI): 6.348 (4.720, 8.538)] were found to be risk factors for DED symptoms in patients with COVID-19 as well as controls. For patients with COVID-19, the length of hospital stay [ORs (95%CI): 1.196 (1.134, 1.262)], use of contact lenses [ORs (95%CI): 20.423 (2.680, 155.632)], history of corneal refractive surgery [ORs (95%CI): 2.166 (1.321, 3.553)], poor sleep quality [ORs (95%CI): 3.650 (2.381, 5.597)], and VDT use for more than 8h per day [ORs (95%CI): 7.740 (4.918, 12.180)] were significant risk factors for DED symptoms. CONCLUSION: Patients with COVID-19 are more prone to develop symptomatic DED. SARS-CoV-2 infection and length of hospital stay are important risk factors for DED symptoms.

Nanoparticle-based drug delivery systems, which can overcome the challenges associated with poor aqueous solubility and other harmful side effects of drugs, display potent applications in cataract treatment. Herein, we designed a nanosystem of gold nanoparticles containing resveratrol (RGNPs) as an anti-aging agent to delay cataracts. The spherical RGNPs had a superior ability to inhibit hydrogen peroxide-mediated oxidative stress damage, including reactive oxygen species (ROS) production, malondialdehyde (MDA) generation, and glutathione (GSH) consumption in the lens epithelial cells. Additionally, the present data showed that RGNPs could delay cellular senescence induced by oxidative stress by decreasing the protein levels of p16 and p21, reducing the ratio of BAX/BCL-2 and the senescence-associated secretory phenotype (SASP) in vitro. Moreover, the RGNPs could also clearly relieve sodium selenite-induced lens opacity in a rat cataract model. Our data indicated that cell senescence was reduced and cataracts were delayed upon treatment with RGNPs through activating the Sirt1/Nrf2 signaling pathway. Our findings suggested that RGNPs could serve as an anti-aging ingredient, highlighting their potential to delay cataract development.

To investigate the levels and clinical relevance of serum β-amyloid (Aβ) in age-related cataract (ARC) patients. In the present study, an overall of 402 ARC patients and 450 normal controls were recruited between June 2018 and December 2019. Serum Aβ1-40 and Aβ1-42 concentrations were assessed by Elisa. The ARC patients were further grouped into several subgroups according to gender, age, types of ARC, and degree of lens opacity. The association of Aβ levels with ARC was determined using logistic regression models. ARC patients had significantly higher serum Aβ1-40 and Aβ1-42 levels than normal control. A similar finding was observed in subjects aged over 60 years. Serum Aβ concentrations were significant correlated with the degrees of lens opacity in C-ARC and N-ARC subjects. Logistic regression analyses revealed that serum Aβ1-40 (ORs = 1.202, 95% CI 1.077 to 1.341) and Aβ1-42 (ORs = 1.686, 95% CI 1.351 to 2.103) levels were potential risk factors for ARC. ARC patients have higher serum Aβ1-40, as well as Aβ1-42 levels, which may reflect an association between Aβ and ARC pathogenesis. Serum Aβ1-42 and Aβ1-40 levels are potential risk factors for ARC.

To compare the efficacy and toxicity of irinotecan-based chemotherapy (IBC) and non-irinotecan-based chemotherapy (NIBC) as first-line treatment for stage IIIB/IV non-small cell lung cancer (NSCLC). PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), abstracts from the annual meetings of ASCO and the ESMO up to 2014 were searched for randomized controlled trials (RCTs) that compared IBC with NIBC. Data on overall survival (OS) and progression-free survival (PFS) were meta-analyzed to provide hazard ratios (HRs), while data on overall response rate (ORR) and frequencies of toxicity were meta-analyzed to provide relative risk ratios (RR). Seven RCTs (6 RCTs from Asian population and 1 from non-Asian population) involving 1473 patients with previously untreated stage IIIB/IV NSCLC were included in the meta-analysis. IBC and NIBC were associated with similar ORR (RR: 1.08, 95 %CI: 0.94 to 1.23, p = 0.30), OS (HR: 0.97, 95 %CI: 0.88 to 1.07, p = 0.56), and PFS (HR: 1.02, 95 %CI: 0.97 to 1.08, p = 0.38). However, the subgroups between Asian and non-Asian patients differed significantly in OS (HR: 0.94 vs 1.87, p = 0.007). There was no significant difference for hematological toxicity (RR: 0.79, 95 %CI: 0.60 to 1.04, p = 0.09) and significant worse for non-hematological toxicity (RR: 2.28, 95 %CI: 1.60 to3.24, p < 0.001), when IBC compared to NIBC. As the available evidence suggests that IBC and NIBC are equivalent in terms of ORR, PFS, OS, at least in Asian patients, we recommend that IBC be considered as a first-line treatment in Asian patients with stage IIIB/IV NSCLC. However, the non-hematological toxicity of IBC must be considered.