Association of exposure to ultraviolet radiation and warm-season ozone air pollution with incident age-related macular degeneration: A nationwide cohort study in China.

BACKGROUND: As the leading cause of blindness, age-related macular degeneration (AMD) performs an adverse impact on human health and disability. AMD have been reported to be associated with environmental factors; however, the association between ultraviolet (UV) radiation, warm-season ambient ozone pollution, and incident AMD remains unclear. METHODS: In this study, 19,707 participants without AMD at baseline were included from a nationwide longitudinal cohort in China. UV radiation and warm-season ozone exposure were evaluated through satellite-based models. Incident AMD was diagnosed via ophthalmological fundus images. Cox proportional hazard regression models were employed to explore the association of UV radiation and warm-season ozone with incident AMD, and the hazard ratios (HRs) and 95 % confidence intervals (CIs) were reported. RESULTS: During 312,935 person-month of follow-up, 3774 participants developed to AMD. High exposure to both UV radiation and warm-season ozone was associated with increasing risk of incident AMD, with HRs and 95 % CIs of 1.32 (1.23, 1.41) and 1.20 (1.11, 1.29) in two-exposure models, respectively. Moreover, negative interaction between UV radiation and warm-season ozone was identified, and it was found that exposure to high UV radiation and low ozone presented the highest hazard for AMD. Subgroup analyses showed that the UV-AMD association was stronger in southern China, while the ozone-AMD association was greater in northern China and rural areas. CONCLUSION: Our study provides the first epidemiological evidence that both UV radiation and warm-season ozone would elevate the risk of incident AMD, and the hazard of higher UV radiation may be attenuated by exposure to ozone. Strategies for decreasing AMD burden should jointly consider environmental exposures and geographic locations.

Soil warming affects sap flow and stomatal gas exchange through altering functional traits in a subtropical forest.

Climate warming influences the structure and function of ecosystems. However, the mechanisms of plant water use and gas exchange responses to climate warming have been less studied, especially from the perspective of different functional traits. We conducted a field experiment to investigate how soil warming (+2 °C) affects sap flow and stomatal gas exchange through plant functional traits and nutrient characteristics in a subtropical forest. We measured stomatal gas exchange of trees (Acacia auriculiformis and Schima superba) and shrubs (Castanea henryi and Psychotria asiatica), and monitored long-term sap flow of both tree species. Besides, plant leaf nutrient contents, functional traits, and soil nutrients were also studied. It is demonstrated that soil warming significantly increased maximum sap flow density (Js_max, 35.1 %) and whole-tree transpiration (EL, 46.0 %) of A. auriculiformis, but decreased those of S. superba (15.6 % and 14.9 %, respectively). Warming increased the photosynthetic rate of P. asiatica (18.0 %) and water use efficiency of S. superba (47.2 %). Leaf nutrients and stomatal anatomical characteristics of shrubs were less affected by soil warming. Soil warming increased (+42.7 %) leaf K content of A. auriculiformis in dry season. Decomposition of soil total carbon, total nitrogen, and available nitrogen was accelerated under soil warming, and soil exchangeable Ca2+ and Mg2+ were decreased. Trees changed stomatal and anatomic traits to adapt to soil warming, while shrubs altered leaf water content and specific leaf area under soil warming. Warming had a greater effect on sap flow of trees, as well as on their leaf gas exchange (total effect: -0.27) than on that of shrubs (total effect: 0.06). In summary, our results suggest that the combination of functional and nutrient traits can help to better understand plant water use and gas exchange responses under climate warming.

Chronic obstructive pulmonary disease alters the genetic landscape and tumor immune microenvironment in lung cancer patients.

Background: Chronic obstructive pulmonary disease (COPD) and lung cancer are leading causes of morbidity and mortality worldwide. Studies have reported molecular alterations in patients with lung cancer and in patients with COPD. However, few investigation has been conducted on the molecular characteristics of lung cancer patients with COPD. Materials and methods: We performed a retrospective cohort study that included 435 patients with pathologically confirmed lung cancer at the Ruijin Hospital. For patients with documented spirometry, Global Initiative for Chronic Obstructive Lung Disease criteria were used to define COPD. For patients without documented spirometry, chest computed tomography and other clinical information were used to define COPD. Tumor tissue DNA was extracted from formalin-fixed paraffin-embedded samples. DNA mutation analysis, multiplex immunohistochemistry (mIHC), calculation of tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and predication of neoantigens were performed. Results: Although SNV mutations in lung cancer patients with COPD (G1 group) were generally higher than those in lung cancer patients without COPD (G2 group), the difference in the number of mutations was insignificant between the two groups. Of the 35 mutated genes, the number of them was higher in G1 than in G2, except that of EGFR. PI3K-Akt signaling pathway was enriched from significantly different genes. While TMB and MATH levels were not significantly different, the tumor neoantigen burdenwas markedly higher in G1 than that in G2. The level of CD68+ macrophages was significant higher in the stroma and total areas in the G1 group than in G2 group. The level of CD8+ lymphocytes was markedly higher in the stroma and showed a clear tendency forhigher expression in the G1 group than inthe G2 group. No significant differences were observed for the level of programmed death-ligand 1+ (PD-L1+), programmed death 1+ (PD-1+), and CD68PD-L1 in the stroma, tumor and total areas. Conclusion: Our study revealed different genetic aberrations and pathways, higher neoantigen burden, and higher level of CD68+ macrophages and CD8+ T lymphocytes in lung cancer patients with COPD. Our investigation implies that the existence of COPD should be considered and immunotherapy is a potential choice when treating lung cancer patients with COPD.

Eosinophil and IFN-γ associated with immune-related adverse events as prognostic markers in patients with non-small cell lung cancer treated with immunotherapy.

Objectives: Immune checkpoint inhibitors (ICIs) alone or combined with other antitumor agents are largely used in lung cancer patients, which show both positive effects and side effects in particular subjects. Our study aims to identify biomarkers that can predict response to immunotherapy or risk of side effects, which may help us play a positive role and minimize the risk of adverse effects in clinical practice. Methods: We retrospectively collected data from patients with advanced non-small cell lung cancer (NSCLC) treated with ICIs at our center. Patients who received initial ICI therapy for >1 year without progression of disease were classified as long-term treatment (LT) group, while others were classified as the non-long-term treatment (NLT) group. Multivariate logistic analysis was performed to identify independent risk factors of progression-free survival (PFS) and immune-related adverse events (irAEs). Results: A total of 83 patients (55.7%) had irAEs. The median PFS for patients in grades 1-2 of irAEs vs. grades 3-4 vs non-irAEs groups was (undefined vs. 12 vs. 8 months; p = 0.0025). The 1-year PFS rate for multisystem vs. single vs. non-irAE groups was 63%, 56%, and 31%, respectively. Signal transduction of inflammatory cytokines improves clinical prognosis through immunomodulatory function, but the benefit is also limited by the resulting organ damage, making it a complex immune balance. Serum biomarkers including EOS% of ≥ 1.15 (HR: 8.30 (95% CI, 2.06 to 33.42); p = 0.003) and IFN-γ of ≥ 3.75 (HR: 5.10 (95% CI, 1.29 to 20.15), p = 0.02) were found to be predictive for irAEs. Conclusion: EOS% of ≥1.15% and IFN-γ of ≥3.75 ng/L were considered peripheral-blood markers for irAEs and associated with improved clinical outcomes for immunotherapy in patients with advanced NSCLC.

Residential greenness exposure and decreased prevalence of diabetic retinopathy: A nationwide analysis in China.

OBJECTIVE: Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness among diabetics. We aimed to explore whether long-term exposure to residential greenness was beneficial to DR. RESEARCH DESIGN AND METHODS: We used data from a large-scale, cross-sectional screening survey conducted in 129 cities of 27 provincial regions of China from 2018 to 2021 among patients with diabetes. We measured residential greenness exposure as the 3-year average of annual maximum Normalized Difference Vegetation Index (NDVI) at a spatial resolution of 250 m. DR was assessed by ophthalmologists based on fundus photographs. The primary outcome was DR, and secondary outcome included DR severity status (i.e., nonproliferative and proliferative), hallmarks of retinal lesions and macular oedema. RESULTS: A total of 484,380 adult participants with diabetes were included in the current analysis, and 15.7% of them were diagnosed with DR. NDVI was inversely and linearly associated with DR prevalence, and an increment of 0.1 NDVI was associated with a 10% (9%-10%) decrease in DR prevalence. Significant and inverse associations were further found for nonproliferative and proliferative DR, hallmarks of lesions and macular oedema. The association between greenness and DR was stronger among participants who were older, obese, lived in the south, had longer duration of diabetes or did not take antidiabetic medications. CONCLUSIONS: This large-scale nationwide study provides the first-hand epidemiological evidence on the associations of residential greenness with DR. Our findings highlight the importance of residential greenness in alleviating DR risk especially in an era of aging and urbanization.

Risk of reactive cutaneous capillary endothelial proliferation induced by camrelizumab in patients with non-small cell lung cancer: a retrospective study.

Background: Reactive cutaneous capillary endothelial proliferation (RCCEP) is a common immune-related adverse event (irAE) related to camrelizumab. This study aimed to investigate the risk factors of RCCEP and its association with patients' survival. Methods: This retrospective study collected the data of consecutive patients with non-small cell lung cancer (NSCLC) who received camrelizumab between January 2019 and December 2021. Baseline characteristics and peripheral blood biomarkers were collected. The outcomes were the occurrence of RCCEP and progression-free survival (PFS). The factors associated with RCCEP were analyzed using univariable and multivariable logistic regression. The association between PFS and RCCEP occurrence was analyzed by the log-rank test. Results: Among the 80 patients included, 24 (30.0%) developed RCCEP, and 56 did not. Among the patients with RCCEP, only four reported the occurrence of grade 3-4 RCCEP. The multivariable analysis revealed that a percentage of eosinophil (EOS%) >1.75% was significantly associated with a higher risk of RCCEP [odds ratio (OR) =4.484; 95% confidence interval (CI): 1.139-17.651] and camrelizumab combined with an anti-angiogenic agent was significantly associated with a lower risk of RCCEP (OR =0.188; 95% CI: 0.055-0.639). The median PFS was numerically longer in patients with RCCEP than in those who did not (17 vs. 9 months, P=0.069). Patients who had baseline EOS% >1.75% and received camrelizumab without an anti-angiogenic agent had a longer median PFS than those who did not (17 vs. 9 months, P=0.011). Conclusions: Baseline EOS% >1.75% and camrelizumab without an anti-angiogenic agent were risk factors of RCCEP and might be associated with better survival in patients with NSCLC.

Use of GLP-1 Receptor Agonists and Occurrence of Thyroid Disorders: a Meta-Analysis of Randomized Controlled Trials.

The association between glucagon-like peptide-1 (GLP-1) receptor agonists and the risk of various kinds of thyroid disorders remains uncertain. We aimed to evaluate the relationship between the use of GLP-1 receptor agonists and the occurrence of 6 kinds of thyroid disorders. We searched PubMed (MEDLINE), EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and Web of Science from database inception to 31 October 2021 to identify eligible randomized controlled trials (RCTs). We performed meta-analysis using a random-effects model to calculate risk ratios (RRs) and 95% confidence intervals (CIs). A total of 45 trials were included in the meta-analysis. Compared with placebo or other interventions, GLP-1 receptor agonists' use showed an association with an increased risk of overall thyroid disorders (RR 1.28, 95% CI 1.03-1.60). However, GLP-1 receptor agonists had no significant effects on the occurrence of thyroid cancer (RR 1.30, 95% CI 0.86-1.97), hyperthyroidism (RR 1.19, 95% CI 0.61-2.35), hypothyroidism (RR 1.22, 95% CI 0.80-1.87), thyroiditis (RR 1.83, 95% CI 0.51-6.57), thyroid mass (RR 1.17, 95% CI 0.43-3.20), and goiter (RR 1.17, 95% CI 0.74-1.86). Subgroup analyses and meta-regression analyses showed that underlying diseases, type of control, and trial durations were not related to the effect of GLP-1 receptor agonists on overall thyroid disorders (all P subgroup > 0.05). In conclusion, GLP-1 receptor agonists did not increase or decrease the risk of thyroid cancer, hyperthyroidism, hypothyroidism, thyroiditis, thyroid mass and goiter. However, due to the low incidence of these diseases, these findings need to be examined further. Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/prospero/, identifier: CRD42021289121.

Functional recovery after intravitreal bevacizumab treatments for idiopathic choroidal neovascularization in young adults.

PURPOSE: To evaluate the morphology and functional recovery of the retina after treatment of idiopathic choroidal neovascularization using intravitreal injections of bevacizumab in young adults. METHODS: For this interventional case series, 20 eyes of 19 patients with idiopathic choroidal neovascularization were treated with multiple intravitreal injections of bevacizumab. Changes in best-corrected visual acuity before the treatment and at follow-up visits were recorded. Structural changes were evaluated using optical coherence tomography and functional changes were assessed using microperimetry. RESULTS: Twenty eyes were followed for 12 months after their first injection. The eyes underwent an average of 3.95 injections. All eyes had a stable or an improved vision. The mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.43 to 0.06 (Wilcoxon signed-ranks test, P < 0.005). Improvement in macular function was detected as early as 1 month after the treatment and lasted for at least 6 months. Microperimetry demonstrated that mean retinal sensitivities within the central 10° field (10.29 ± 5.12 dB) at baseline improved to 13.98 ± 3.96 dB at the last visit. Dense scotomas were found in 13 of the 20 eyes at baseline and 5 of the 20 eyes at the last visit. Stable fixation (6 of 20 at baseline) was found in 17 of the 20 eyes at the last visit. Twelve of the 14 eyes with either a predominantly eccentric or poor central fixation at baseline established central fixation at 12 months. No serious local or systemic complications were encountered. CONCLUSION: In young adults with idiopathic choroidal neovascularization, an improvement in visual acuity and macular function was detected after intravitreal injections of bevacizumab.

The antiangiogenic effects of integrin alpha5beta1 inhibitor (ATN-161) in vitro and in vivo.

PURPOSE: Integrin α5ß1 is involved in the development of choroidal neovascularization (CNV). Thus, the inhibition of integrin α5ß1 may provide an alternative to the current standard of CNV therapy, which involves inhibition of vascular endothelial growth factor (VEGF) and is not effective in all patients. This study evaluated the antiangiogenic effects of ATN-161, a small peptide inhibitor of integrin α5ß1, in human choroidal endothelial cells (hCECs) and in laser-induced CNV in rats. Furthermore, the utility of spectral-domain optical coherence tomography (SD-OCT) for dynamic observation of the development of CNV in animal models was assessed. METHODS: The antiangiogenic potential of ATN-161 was evaluated in VEFG-stimulated hCECs by MTS proliferation assays, migration assays, and synthetic matrix capillary tube formation assays. To evaluate the antiangiogenic effects of ATN-161 in vivo, CNV was induced in rats by laser photocoagulation. ATN-161, scrambled peptide, or AF564 anti-VEGF antibody, were injected intravitreally immediately after photocoagulation. Eyes were examined by SD-OCT and fluorescein angiography on days 1, 7, and 14 after injection, and the areas of CNV were measured by analysis of choroidal flatmounts at day 14. RESULTS: ATN-161 inhibited VEGF-induced migration and capillary tube formation in hCECs, but did not inhibit proliferation. In vivo, injection of ATN-161 after laser photocoagulation inhibited CNV leakage and neovascularization to an extent similar to AF564. Furthermore, SD-OCT and histologic examinations indicated that ATN-161 significantly decreased the size of laser-induced lesions. CONCLUSIONS: Integrin α5ß1 inhibition by ATN-161 may be a promising alternative therapy for CNV-related angiogenesis. In addition, SD-OCT technology allows excellent visualization of experimentally induced CNV in vivo.