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There is limited evidence regarding the effects of long-term exposure to PM 2.5 constituents on the risk of arthritis and rheumatoid arthritis, and the interaction between PM 2.5 and green space remains unclear. This study examined the relationship between long-term exposure to PM 2.5 constituents and the risk of arthritis and rheumatoid arthritis, with the exposure period extending from recruitment until self-reported outcomes, death, loss to follow-up, or end of follow-up. Additionally, the study assessed whether there was an interactive effect between PM 2.5 and green space on these risks. We gathered cohort data on 18,649 individuals aged ≥45 years. We applied generalized linear mixed-effects models to estimate the effects of PM 2.5 constituents, NDVI, and their interaction on arthritis and rheumatoid arthritis. The quantile g-computation and weighted quantile sum regression model were applied to estimate the combined effect of PM 2.5 constituents. Our results showed that exposure to single and mixed PM 2.5 constituents adversely affected arthritis and rheumatoid arthritis, and was mainly attributed to the black carbon component. We observed "U" or "J" shaped exposure-response curves for the effects of PM 2.5 , OM, NO 3 - and NH 4 + exposure on the development of arthritis/rheumatoid arthritis. Additionally, the odds ratio of arthritis for per interquartile range (IQR) increase in PM 2.5 was 1.209 (95% CI:1.198, 1.221), per 0.1-unit decrease in NDVI was 1.091 (95% CI:1.033, 1.151), and the interaction term was 1.005 (95% CI:1.002, 1.007). These findings flesh out the existing evidence for PM 2.5 constituents, NDVI and arthritis, rheumatoid arthritis, but the underlying mechanisms still require further exploration., Competing Interests: The authors declare no conflicts of interest relevant to this study., (© 2024 The Author(s). GeoHealth published by Wiley Periodicals LLC on behalf of American Geophysical Union.)

To assess the level of both pro-inflammatory and anti-inflammatory cytokines in the aqueous humor (AH) of patients suffering from uveitis, with or without coexisting glaucoma, and compare them with patients diagnosed with primary open-angle glaucoma (POAG) and those with age-related cataract (ARC). By using Luminex xMAP® multiplex assays analyses, we assessed levels of 11 cytokines and chemokines, and compared them across groups, including uveitis-secondary glaucoma (USG) (n = 16), uveitis without glaucoma (UwoG), (n = 16), POAG (n = 16), and ARC (n = 16) to explore the correlation between these cytokines and the presence of uveitis, as well as intraocular pressure (IOP). Pro-inflammatory factors MCP-1, MIP-1β, IL-6, IL-8, and transforming growth factors TGF-β1 and TGF-β2 were significantly elevated in the AH of USG eyes. In the case of enhanced anti-inflammatory in the perioperative period, the pro-inflammatory factors remained notably elevated in the USG group compared to the UwoG group (P < 0.01). The levels of IL-6, IL-8, and MCP-1 in the AH of the USG group and POAG group had the same trend, which markedly surpassed those of the ARC group (P < 0.01). Significantly increased levels of MCP-1, MIP-1β, IL-6, IL-8, TGF-β1, and TGF-β2 were found in the AH of USG patients, implying a potential role for these mediators in the progression of glaucomatous manifestations within patients with uveitis. Besides the analysis revealed no discernible statistical disparity in cytokine concentrations within the AH of USG eyes whether the preoperative baseline IOP was greater than 30 mmHg or not, indicating that the safety of antiglaucoma surgery in USG patients even with baseline high IOP., (© 2024. The Author(s).)

The study aimed to investigate the pattern and trend of Musculoskeletal (MSK) disorders in people aged 5-19 years from 1990 to 2021. The data was sourced from the Global Burden of Disease study 2021. The Age-standardized DALYs rates (ASDR), age-standardized mortality rate (ASMR), age-standardized prevalence rate (ASPR), and age-standardized incidence rate (ASIR) and their corresponding average annual percent change (AAPC) for MSK disorders were evaluated by sex, region, and sociodemographic index (SDI) quintiles. Globally, the ASPR of MSK disorders among children and adolescents increased per 100,000 population from 3048.66 (95% confidence interval [CI]: 2336.68-3887.02) in 1990 to 3105.46 (95% CI: 2421.09-3904.95) in 2021 (AAPC 0.06 [95% CI: 0.05-0.07]). In 2021, individuals aged 15-19 experienced the highest burden compared to those aged 5-9 and 10-14. In 2021, high SDI countries had the highest ASIR, ASPR, ASDR of MSK disorders. The AAPC of ASPR in high SDI countries showed a stark contrast to that in low SDI countries for the same period (AAPC 0.48 vs. AAPC -0.03). From 1990 to 2021, in low SDI and low-middle SDI countries, the increase in DALYs was primarily due to population growth. However, in middle SDI, high-middle, and high SDI countries, the increases were mainly due to epidemiological changes. Globally, patients aged 10-14 experienced better care compared to those in the 5-9 and 15-19 age groups. Specific preventive health measures are needed for females and adolescents aged 15-19 in high SDI countries., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To develop diagnostic recommendations for diffuse large B-cell vitreoretinal lymphoma (VRL) in Chinese patients., Methods: Retrospective observational case series. Seventy-three eyes of 40 VRL patients and 8 control patients were analyzed. Eighteen patients from Beijing Tongren Hospital and 46 patients from literature were involved as validations., Results: Diagnostic methods included (1) typical clinical manifestations; (2) vitreous cytology; (3) immunohistochemical examination of vitreous or choroid/retina; (4) aqueous humor or vitreous cytokine; (5) vitreous cell gene rearrangement; (6) vitreous flow cytometry. If patients meet (1)+(2)+(3), or if they meet (1), and two of (4), (5), (6) are positive, they can be diagnosed as VRL. The sensitivity and specificity values for accurate diagnosis were 0.975 and 1.00. One hundred percent eyes from Beijing Tongren Hospital and 92.7% eyes from literature can be diagnosed., Conclusion: We developed diagnostic recommendations for diffuse large B-cell VRL through vitreous cytology combined with multiple auxiliary examinations.

Objective: To evaluate the associations between biological aging, metabolic heterogeneity of obesity, and rheumatoid arthritis (RA)., Methods: This prospective cohort study analyzed 268,184 individuals from the UK Biobank. Biological age was estimated using phenotypic age (PhenoAge), Klemera-Doubal methods (KDM-BA), and telomere length. We calculated KDM-BA acceleration and PhenoAge acceleration after subtracting the effect of chronological age by regression residual. The metabolic heterogeneity of obesity can be evaluated by four BMI metabolic phenotypes, namely metabolically unhealthy normal weight (MUNW), metabolically healthy normal weight (MHNW), metabolically unhealthy overweight/obesity (MUOO), and metabolically healthy overweight/obesity (MHOO). Cox models were employed to estimate the associations between biological aging, metabolic heterogeneity of obesity, and RA risk., Results: A total of 2842 patients experienced RA during a mean follow-up time of 12.21 years. A standard deviation (SD) increase in KDM-BA acceleration and PhenoAge acceleration was associated with an increased risk of RA by 13% (hazard ratio = 1.13; 95% CI, 1.09-1.17) and 39% (HR = 1.39; 95% CI, 1.34-1.44), respectively. A SD increase in telomere length was associated with a reduced risk of RA by 5% (HR = 0.95; 95% CI, 0.91-0.98). Compared to the MHNW group, the MUOO group was associated with a 51% increase in the risk of incident RA. In the joint effect analysis, compared to the MHNW + KDM-BA younger subgroup, the HR (95% CI) for RA was 1.68 (1.48, 1.90) in the MUOO + KDM-BA older subgroup., Conclusion: Accelerated biological aging may heighten the susceptibility to RA, particularly in individuals with obesity or metabolic dysfunction. Key Points •Accelerated biological aging increases the risk of developing RA. •Overweight/obese people with a healthy metabolism have a higher risk of RA than those with normal weight and healthy metabolism. •The BMI metabolic phenotype has a strong modifying effect on the association between KDM-BA/PhenoAge and RA risk., Competing Interests: Declarations. Ethics approval: All individuals involved provided written approval, and the North West-Haydock Research Ethics Committee approved the study (16/NW/0274). Disclosures: None., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Purpose: To explore if COVID-19 infection and its subsequent immunosuppressant adjustment as well as previous vaccination status are associated with higher risks of uveitis flare in patients with Behcet's disease., Methods: This retrospective multicenter cohort study was conducted in January 2023 among patients with Behcet's uveitis, during the second wave of the COVID-19 pandemic in China, with an anticipated sample size of 250. The primary objective was to examine the association between COVID-19 infection and the occurrence of uveitis flare. The potential impact of other exposures, including the patient's vaccination status and treatment adjustments to the risk of uveitis flare and the course of COVID-19 infection were also analyzed., Results: 207 patients with COVID-19 infection and 47 patients without COVID-19 infection were included. A total of 127 uveitis flares occurred in the observational period (14.29 events per 100 person-month). COVID-19 infection was found to be significantly associated with a higher rate of uveitis flare (adjusted rate ratio = 4.8, 95% CI 3.7 to 6.3, P < 0.001). However, neither systemic immunosuppressive adjustment nor COVID-19 vaccination status showed a significant association with uveitis flare or the course of COVID-19 infection., Conclusions: This study provides evidence of an association between COVID-19 infection and an increased risk of uveitis flare in patients with Behcet's disease. However, there was no significant evidence to support that baseline immunosuppressive therapy regimens, treatment adjustment after COVID-19 infection, or vaccination status were associated with higher risks of uveitis flare or prolonged COVID-19 course., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Current diabetic retinopathy (DR) treatment involves blood glucose regulation combined with laser photocoagulation or intravitreal injection of vascular endothelial growth factor (VEGF) antibodies. However, due to the complex pathogenesis and cross-interference of multiple biochemical pathways, these interventions cannot block disease progression. Recognizing the critical role of the retinal microenvironment (RME) in DR, it is hypothesized that reshaping the RME by simultaneously inhibiting primary and secondary blood-retinal barrier (BRB) injury can attenuate DR. For this, a glucose-responsive hydrogel named Cu-PEI/siMyD88@GEMA-Con A (CSGC) is developed that effectively delivers Cu-PEI/siMyD88 nanoparticles (NPs) to the retinal pigment epithelium (RPE). The Cu-PEI NPs act as antioxidant enzymes, scavenging ROS and inhibiting RPE pyroptosis, ultimately blocking primary BRB injury by reducing microglial activation and Th1 differentiation. Simultaneously, MyD88 expression silence in combination with the Cu-PEI NPs decreases IL-18 production, synergistically reduces VEGF levels, and enhances tight junction proteins expression, thus blocking secondary BRB injury. In summary, via remodeling the RME, the CSGC hydrogel has the potential to disrupt the detrimental cycle of cross-interference between primary and secondary BRB injury, providing a promising therapeutic strategy for DR., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objective: To investigate the age-standardized prevalence rate (ASPR) and temporal trends for hip, knee, hand, and other osteoarthritis (OA) at a global, continental, and national level., Design: The estimates and 95% uncertainty intervals (UIs) for case number and ASPR of OA were derived from the Global Burden of Diseases Study (GBD) 2019. The joinpoint regression analysis was utilized to examine the temporal trends from 1990 to 2019., Results: In 2019, the global ASPR of hip, knee, hand, and other OA was 400.95 (95% UI: 312.77-499.41), 4375.95 (95% UI: 3793.04-5004.9), 1726.38 (95% UI: 1319.91-2254.85), and 745.62 (95% UI: 570.16-939.8). As for the ASPR of hip OA, hand OA, and other OA, Europe and America had higher rates than Asia and Africa, and Asia was second only to America in knee OA ASPRs. The period 1990-2019, the ASPR at global level dropped significantly for hand OA (AAPC = -0.4%, 95% CI: -0.47 to -0.34) and increased significantly for hip OA (AAPC = 0.43%, 95% CI: 0.39-0.46), knee OA (AAPC = 0.17%, 95% CI: 0.09-0.24) and other OA (AAPC = 0.16%, 95% CI: 0.15-0.17). Different continents, countries, and periods demonstrated significant changes., Conclusions: Globally, America has the highest OA burden and Asia has a higher knee OA burden. Appropriate prevention and control measures to reduce modifiable risk factors are needed to reduce the burden of OA., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Purpose: Behçet's disease-associated uveitis (BDU) is a severe, recurrent inflammatory condition affecting the eye and is part of a systemic vasculitis with unknown etiology, making biomarker discovery essential for disease management. In this study, we intend to investigate potential urinary biomarkers to monitor the disease activity of BDU., Methods: Firstly, label-free data-dependent acquisition (DDA) and tandem mass tag (TMT)-labeled quantitative proteomics methods were used to profile the proteomes of urine from active and quiescent BDU patients, respectively. For further exploration, the remaining fifty urine samples were analyzed by a data-independent acquisition (DIA) quantitative proteomics method., Results: Twenty-nine and 21 differential proteins were identified in the same urine from BDU patients by label-free DDA and TMT-labeled analyses, respectively. Seventy-nine differentially expressed proteins (DEPs) were significantly changed in other active BDU urine samples compared to those in quiescent BDU urine samples by IDA analysis. Gene Ontology (GO) and protein-protein interaction (PPI) analyses revealed that the DEPs were associated with multiple functions, including the immune and neutrophil activation responses. Finally, seven proteins were identified as candidate biomarkers for BDU monitoring and recurrence prediction, namely, CD38, KCRB, DPP4, FUCA2, MTPN, S100A8 and S100A9., Conclusions: Our results showed that urine can be a good source of biomarkers for BDU. These dysregulated proteins provide potential urinary biomarkers for BDU activity monitoring and provide valuable clues for the analysis of the pathogenic mechanisms of BDU., (© 2024. The Author(s).)

Introduction: Air pollution is speculated to increase the risk of Coronavirus disease-2019 (COVID-19). Nevertheless, the results remain inconsistent and inconclusive. This study aimed to explore the association between ambient air pollution (AAP) and COVID-19 risks using a meta-analysis with meta-regression modelling., Methods: The inclusion criteria were: original studies quantifying the association using effect sizes and 95 % confidence intervals (CIs); time-series, cohort, ecological or case-crossover peer-reviewed studies in English. Exclusion criteria encompassed non-original studies, animal studies, and data with common errors. PubMed, Web of Science, Embase and Google Scholar electronic databases were systemically searched for eligible literature, up to 31, March 2023. The risk of bias (ROB) was assessed following the Agency for Healthcare Research and Quality parameters. A random-effects model was used to calculate pooled risk ratios (RRs) and their 95 % CIs., Results: A total of 58 studies, between 2020 and 2023, met the inclusion criteria. The global representation was skewed, with major contributions from the USA (24.1 %) and China (22.4 %). The distribution included studies on short-term (43.1 %) and long-term (56.9 %) air pollution exposure. Ecological studies constituted 51.7 %, time-series-27.6 %, cohorts-17.2 %, and case crossover-3.4 %. ROB assessment showed low (86.2 %) and moderate (13.8 %) risk. The COVID-19 incidences increased with a 10 μg/m 3 increase in PM 2.5 [RR = 4.9045; 95 % CI (4.1548-5.7895)], PM 10 [RR = 2.9427: (2.2290-3.8850)], NO 2 [RR = 3.2750: (3.1420-3.4136)], SO 2 [RR = 3.3400: (2.7931-3.9940)], CO [RR = 2.6244: (2.5208-2.7322)] and O 3 [RR = 2.4008: (2.1859-2.6368)] concentrations. A 10 μg/m 3 increase in concentrations of PM 2.5 [RR = 3.0418: (2.7344-3.3838)], PM 10 [RR = 2.6202: (2.1602-3.1781)], NO 2 [RR = 3.2226: (2.1411-4.8504)], CO [RR = 1.8021 (0.8045-4.0370)] and O 3 [RR = 2.3270 (1.5906-3.4045)] was significantly associated with COVID-19 mortality. Stratified analysis showed that study design, exposure period, and country influenced exposure-response associations. Meta-regression model indicated significant predictors for air pollution-COVID-19 incidence associations., Conclusion: The study, while robust, lacks causality demonstration and focuses only on the USA and China, limiting its generalizability. Regardless, the study provides a strong evidence base for air pollution-COVID-19-risks associations, offering valuable insights for intervention measures for COVID-19., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Purpose: To develop a more tailored immunomodulatory treatment (IMT) strategy based on a novel 2-arm risk stratification system in Vogt-Koyanagi-Harada (VKH) patients., Design: A retrospective clinical cohort study., Methods: Seventy-nine VKH patients in the acute stage were stratified into low- (n = 58) and high-risk (n = 21) groups based on their exposure to risk factors. They were treated with oral glucocorticoids (GCs) plus as-needed (PRN) or first-line IMT. Best corrected visual acuity (BCVA), sunset glow fundus (SGF) occurrence, relapse rate, and systemic adverse events were evaluated during follow-up., Results: Compared with the low-risk group, the high-risk group showed poorer BCVA at baseline (estimated difference 0.51, 95% CI 0.30-0.78; P < .001) and 6-month follow-up (estimated difference 0.08, 95% CI 0.00-0.08; P = .006), higher incidence of SGF at 12 months (52% vs 28%; RR 1.9, 95% CI 1.1-3.4; P = .040), and higher relapse rate at 6 months (24% vs 5%; RR 4.6, 95% CI 1.2-17.5; P = .028) and 12 months (52% vs 12%; RR 4.4, 95% CI 1.9-9.7; P < .001). In the low-risk cohort, no significant difference between the 2 IMT strategies was observed in primary outcomes. In the high-risk cohort, patients with the immediate IMT showed better BCVA (estimated difference -0.20, 95% CI -0.3 to -0.08; P = .007), lower incidence of SGF (27% vs 80%; RR 0.3, 95% CI 0.1-0.9; P = .030), and lower relapse rate (27% vs 80%; RR 0.3, 95% CI 0.1-0.9; P = .030) compared with the PRN regimen. Moreover, the immediate IMT regimen had a higher frequency of systemic adverse events than the PRN regimen (47% vs 7%; RR 7.1, 95% CI 2.5-20.4; P < .001)., Conclusions: High-risk stratification at baseline was associated with poor prognosis. The immediate IMT regimen was only beneficial for high-risk VKH patients regarding visual outcome, SGF, and relapse rate. This study suggests a potential need for a customized IMT strategy for VKH patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Phase-change droplets (PCDs) are intelligent responsive micro and nanomaterials developed based on micro/nano bubbles. Subject to external energy inputs such as temperature and ultrasound, the core substance, perfluorocarbon (PFC), undergoes a phase transition from liquid to gas. This transformation precipitates alterations in the PCDs' structure, size, ultrasound imaging capabilities, drug delivery efficiency, and other pertinent characteristics. This gives them the ability to exhibit "intelligent responses". This study utilized lipids as the membrane shell material and perfluorohexane (PFH) as the core to prepare lipid phase-change droplets. Superparamagnetic nanoparticles (PEG-functionalized Fe 3 O 4 nanoparticles) and the anti-tumor drug curcumin (Cur) were loaded into the membrane shell, forming magnetic drug-loaded phase-change droplets (Fe-Cur-NDs). These nanoscale phase-change droplets exhibited excellent magnetic resonance/ultrasound imaging capabilities and thermal/ultrasound-mediated drug release. The Fe-Cur-NDs showed excellent anti-tumor efficacy for the MCF-7 cells under low-intensity focused ultrasound (LIFU) guidance in vitro . Therefore, Fe-Cur-NDs represent a promising smart responsive theranostic integrated micro/nano drug delivery system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Zhao, Liu, Wang, Ma, Zhang, Xu, Hu and Duan.)

To evaluate the impact of CO2 fractional laser combined with recombinant human epidermal growth factor (rhEGF) gel on skin barrier in acne scar patients. In a retrospective analysis, we examined 105 acne scar patients admitted between July 2018 and August 2021. Of these, 51 received only CO2 fractional laser (control group), while 54 underwent a combination of CO2 fractional laser and rhEGF gel (observation group). We assessed treatment efficacy, symptom relief, skin barrier parameters, pre- and posttreatment inflammatory factors, adverse reactions, posttreatment quality of life, and patient satisfaction. The observation group exhibited a higher overall response rate, significantly shorter wound healing, scab formation, and scab detachment times. Additionally, this group showed increased stratum corneum water content, decreased pH, and transdermal water loss (TEWL), and reduced hypersensitive C-reactive protein and interleukin-6 expression posttreatment. Quality of life scores were higher, with fewer adverse reactions and greater treatment satisfaction. Combining CO2 fractional laser with rhEGF gel markedly improves acne scar treatment efficacy, enhances skin barrier function, reduces inflammation, and elevates quality of life. Its safety profile supports its broader clinical adoption., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Short-term exposure to air pollution may trigger symptoms of drug-resistant tuberculosis (DR-TB) through stimulating lung tissue, damaging tracheobronchial mucosa, the key anti-mycobacterium T cell immune function, and production and release of inflammatory cytokines., Objective: To investigate the association between acute exacerbations of DR-TB and short-term residential exposure to air pollutants (PM 10 , PM 2.5 , SO 2 , NO 2 , CO and O 3 ) based on a large prospective cohort in Anhui Province, China., Method: Patients were derived from a prospective cohort study of DR-TB in Anhui Province. All DR-TB patients underwent drug-susceptibility testing and prefecture-level reference laboratories confirmed their microbiologies. The case-crossover design was performed to evaluate the association between the risk of acute exacerbations of DR-TB and short-term residential exposure to air pollution., Results: Short-term NO 2 exposure was significantly related to an elevated risk of first-time outpatient visit due to acute exacerbations of DR-TB(relative risk:1.159, 95% confidence interval:1.011 ~ 1.329). Stratification analyses revealed that the relationship between the risk of acute exacerbations and NO 2 exposure was stronger in the elderly (age ≥ 65) DR-TB patients, and in individuals with a history of TB treatment., Conclusions: NO 2 Exposure was significantly associated with an elevated risk of acute exacerbation of DR-TB in Anhui Province, China., (© 2024. The Author(s).)

Background: The effects of heavy metal exposure on immunological function have sparked widespread concern, but unequivocal evidence on the association between mixed metal exposure and novel systemic inflammatory indexes remains scarce., Objectives: This study aimed to analyze the associations of heavy metals with two novel systemic inflammation indexes and the mediated effects of serum albumin., Methods: Nineteen metals were detected among 4082 U.S. adults based on the NHANES. A linear regression, restricted cubic splines (RCS) regression, weighted quantile sum (WQS), Quantile-based Gcomputation (qgcomp), and Bayesian kernel machine regression (BKMR) were conducted to evaluate the associations of single metal and mixed metals with systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) levels, respectively. A series of subgroup analyses were used to identify potentially vulnerable populations. Furthermore, we conducted mediation analyses to investigate the mediated effects of serum albumin on the associations of metals with SII and SIRI., Results: In the single-exposure model, exposure to various metals such as urinary Co, As, and serum Zn, Cu was associated with SII and SIRI (P FDR <0.05). Simultaneously, the above metals were linear positively correlated with SII and SIRI. Mixed-exposure analyses consistently showed that overall mixed urinary metal levels were positively pertinent for SII and SIRI levels, and the metal Co played a significant role in the urinary metal mixtures. Subgroup analyses showed that exposure to urinary Cd in men and elderly people increased SII and SIRI levels. The results of mediation analyses suggested the association of urinary metal mixture with SII and SIRI was mediated by albumin, and the proportion of mediation was 14.45% and 9.49%, respectively., Conclusions: Our findings suggested that metal exposure is strongly associated with the levels of system inflammation indexes and that serum albumin is, in part, a mediator of this association., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to examine rheumatoid arthritis (RA) risk associated with hormonal and reproductive factors in women from the large cohort of the UK Biobank., Methods: Data on hormonal and reproductive factors in women were collected from a prospective cohort of 223 526 UK Biobank participants. The potential relationship between reproductive factors and RA risk was assessed using restricted cubic spline. Hazard ratios (HR) were estimated using Cox proportional hazard regressions., Results: During a median follow-up of 12.39 years, 3313 women with RA were identified. Age at menarche >14 years was associated with a greater RA risk (HR 1.13, 95% CI 1.02 to 1.26) compared with menarche at 13. The multiple adjusted HR for RA in women with menopause at <45 years was 1.46. Reproductive years <33 increased the risk of RA (HR 1.39, 95% CI 1.21 to 1.59). Compared with those with 2 children, women with ≥4 children were associated with a higher risk of RA (HR 1.18, 95% CI 1.04 to 1.34). Women who had a hysterectomy (HR 1.40, 95% CI 1.25 to 1.56) or oophorectomy (HR 1.21, 95% CI 1.08 to 1.35) had a higher risk of RA than those without a hysterectomy or oophorectomy. Both hormone replacement therapy (HRT) use (HR 1.46, 95% CI 1.35 to 1.57) and HRT duration (HR 1.02, 95% CI 1.01 to 1.03) were associated with a higher risk of RA., Conclusions: Some hormonal and reproductive factors were associated with a higher risk of RA. Hormonal and reproductive factors should be considered in risk assessment and formulating management plans in female patients with RA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

MicroRNAs (miRNAs) are non-coding RNA molecules that bind to mRNAs to regulate gene expression. Since changes in miRNA expression levels have been found in a variety of autoimmune illnesses, miRNAs are important in autoimmune diseases. MiRNAs serve not only as pathogenic factors and biomarkers for autoimmune diseases but also as important targets for disease therapeutics. Although miRNA-based treatments are still in the research stage, in-depth investigations into the biological functions of miRNAs have significantly enhanced our understanding of their mechanisms in autoimmune diseases. The purpose of this review is to summarize the biological functions of miRNAs, their roles in rheumatoid arthritis and systemic lupus erythematosus, therapeutic strategies, and challenges., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: To develop a sensitive point-of-care testing (POCT) aqueous vascular endothelial growth factor (VEGF) detection system, and assess its role for predicting the response to anti-VEGF treatment in macular edema secondary to retinal vein occlusion (RVO-ME) patients., Methods: An automatic point-of-care aqueous humor Magnetic Particle Chemiluminescence Enzyme Immuno-Assay (MPCLEIA) VEGF detection system was developed. The predictive values of aqueous cytokine levels, in combination with imaging parameters, on anatomical treatment response (ATR, the relative central macular thickness change [ΔCMT/bl-CMT]) were analyzed., Results: The automatic MPCLEIA system was able to provide results in 45 min with only 20 μL sample. Among the 57 eyes with available pre- and post-treatment evaluation, ATR significantly correlated with levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and VEGF measured by Luminex xMAP platform, and VEGF measured by MPCLEIA. Optimal cut-off values for these biomarkers were 13.26 ng/L, 23.57 ng/L, 1,110.12 ng/L, 105.52 ng/L, and 85.39 ng/L, respectively. Univariate analysis showed significant associations between ATR category (good response if ATR≤-25 % or poor response otherwise) and IL-6, IL-8, MCP-1, VEGF-xMAP, and VEGF-MPCLEIA (p<0.05). Multivariate logistic regression revealed that ATR category was significantly associated with aqueous VEGF-MPCLEIA (p=0.006) and baseline(bl)-CMT (p=0.008). Receiver operating characteristics analysis yielded an AUC of 0.959 for the regression model combining VEGF-MPCLEIA and bl-CMT, for predicting ATR category., Conclusions: Our novel MPCLEIA-based automatic VEGF detection system enables accurate POCT of aqueous VEGF, which shows promise in predicting the treatment response of RVO-ME to anti-VEGF agents when combined with bl-CMT., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Osteoarthritis (OA) is a threat to public health issue with high morbidity and disability worldwide. However, unequivocal evidence on the link between air pollution and OA remains little, especially in multi-study sites. This study aimed to explore the relationship between short-term exposure to main air pollutants and the risk of OA outpatient visits in multi-study sites. A multi-city time-series analysis was performed in Anhui Province, Central-Eastern China from January 1, 2015, to December 31, 2020. We used a two-stage analysis to assess the association between air pollution and daily OA outpatient visits. City-specific associations were estimated with a distributed lag nonlinear model and then pooled by random-effects or fixed-effects meta-analysis. Stratified analysis was conducted by gender, age, and season. Additionally, the disease burden of OA attributable to air pollutant exposure was calculated. A total of 35,700 OA outpatients were included during the study period. The pooled exposure-response curves showed that PM 2.5 and PM 10 concentrations below the reference values could increase the risk of OA outpatient visits. Concretely, per 10 ug/m 3 increase in PM 2.5 concentration was linked to an elevated risk of OA outpatient visits at lag 2 and lag 3 days, where the effect reached its highest value on lag 2 day (RR: 1.023, 95%CI: 1.005-1.041). We observed that a 10 μg/m 3 increase in PM 10 was positively correlated with OA outpatient visits (lag2 day, RR: 1.011, 95%CI: 1.001-1.025). Nevertheless, no statistical significance was discovered in gaseous pollutants (including SO 2 , O 3 , and CO). Additionally, a significant difference was found between cold and warm seasons, but not between different genders or age groups. This study reveals that particulate matter is an important factor for the onset of OA in Anhui Province, China. However, there is no evidence of a relationship of gaseous pollutants with OA in this area., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Continued investment in finance and innovation is beneficial to economic development, and the joining of green system can accelerate the process of economic recovery from environmental distress. To better enhance the relationship of green finance and green innovation, it is vital to demonstrate the synergy between the two thoroughly. Thirty provinces in China are selected to examine the coupling coordination relationship between the two, specifically testing the spatial aggregation and evolutionary differences in the coupling coordination by adopting the coupling coordination degree (CCD) model, spatial autocorrelation, and kernel density estimation. Conclusions of the paper show that green finance is calculated by the EW-TOPSIS method, and the overall score of provinces is low. Using super-SBM model to evaluate green innovation, the uneven distribution of efficiency is obvious, although it is gradually increasing. The CCD in most provinces is in low-level or basic coordination, with significant regional heterogeneity. The global Moran's index becomes gradually evident with time. The local Moran scatter diagram presents a downward trend from east to west, but with more L-L aggregation provinces emerging in 2020. The center of the national kernel density curve gradually shifts to the right, indicating that the national overall synergy level is improving. Deepening the understanding of the empirical results facilitates the formulation of reasonable policies that fit the four major regions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Von Willebrand factor (VWF) is an adhesive ligand critical for maintaining hemostasis. However, it has also been increasingly recognized for its role in cancer development because it has been shown to mediate the adhesion of cancer cells to endothelial cells, promote the epithelial-mesenchymal transition, and enhance angiogenesis. We have previously shown that gastric cancer cells synthesize VWF, which mediates the interaction between the cancer and endothelial cells to promote cancer growth. Here, we report results from a clinical observational study that demonstrate the association of VWF in plasma and on the surface of extracellular vesicles (EVs) with the pathological characteristics of gastric cancer. We found that patients with gastric cancer had elevated and intrinsically hyperadhesive VWF in their peripheral blood samples. VWF was detected on the surface of EVs from cancer cells, platelets, and endothelial cells. Higher levels of these VWF-bound EVs were associated with cancer aggression and poor clinical outcomes for patients. These findings suggest that VWF + EVs from different cell types serve collectively as a new class of biomarkers for the outcome assessment of gastric cancer patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To analyze the correlation between cerebrospinal fluid (CSF) interleukin-10 (IL-10) levels and the clinical characteristics in patients with vitreoretinal lymphoma (VRL)., Design: Retrospective observational case series., Methods: Forty-one patients were diagnosed as VRL and underwent lumbar puncture for CSF examination. Aqueous humor cytokine detection, vitreous cytopathologic analysis, monoclonal gene rearrangement, and flow cytometry were performed. The CSF was assessed through biochemical and cytologic examination, flow cytometry, and cytokine detection., Results: The median levels of aqueous humor IL-10 and IL-6 were 415.0 and 40.7 pg/mL. The median CSF levels of IL-10 and IL-6 were 35.7 and 3.5 pg/mL, respectively. IL-10 levels in CSF were higher than normal in 37 patients (90.2%) and higher in patients with intracranial lesions. The level of CSF IL-10 decreased after systemic treatment, and it rose before intracranial lesion onset or recurrence. The level of IL-10 in CSF was related to the duration of ocular symptoms, but was not related to the level of IL-10 in aqueous humor. There was no significant difference in CSF IL-10 levels between patients with and without anterior chamber inflammation or retinal lesions. In eyes with recurrent vitreoretinal lymphoma, the level of IL-10 in aqueous humor increased significantly, but there was no corresponding increase in the level of IL-10 in CSF., Conclusion: CSF IL-10 is a potentially important biomarker in VRL, especially in the monitoring of intracranial lesions., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: N-propylparaben (PP), a type of paraben, is commonly used as a preservative or antibacterial agent in daily chemicals, medicine, food, cosmetics, feed, and various industrial preservatives. Although PP promotes the growth of human breast adenocarcinoma (MCF-7) cells by activating the human estrogen receptor (ER), the mechanism responsible for this type of programmed cell proliferation is poorly understood., Objective: To clarify the effect of PP on cell metabolic function and the potential molecular mechanism of PP induced MCF-7 cell proliferation from a new perspective., Methods: To use high-resolution mass spectrometry-based metabolomics combined with bioinformatics analysis to analyze the molecular mechanism., Results: The results illustrated that differential endogenous compounds related to the effects of PP on cell metabolic functions were detected. PP was found to promote glycolysis in MCF-7 cells and enhance the tricarboxylic acid cycle (TCA cycle) in mitochondria, thus improving the energy supply to these tumor cells for metabolic function and promotion of rapid proliferation. Moreover, we found that PP promoted cell proliferation by affecting the mitogen-activated protein kinase (MAPK) signaling pathway of MCF-7 cells., Conclusion: Our results revealed the molecular mechanism of low concentration PP promoting MCF-7 cell proliferation by activating ER.

Background: Sclerostin, a regulator of bone metabolism and vascular calcification involved in regulating the Wnt/β-catenin signaling pathway, has been shown to be involved in the pathogenesis of rheumatoid arthritis (RA). However, current results regarding the circulating sclerostin level of RA patients are debatable. This study aimed to evaluate the circulating level of sclerostin in RA patients and briefly summarize its role., Method: PubMed, EMBASE, and the Cochrane Library databases were systematically searched till May 27, 2021, for eligible articles. Useful data from all qualified papers were systematically extracted and analyzed using Stata 12.0 software (Stata Corp LP, College Station, TX, USA)., Results: Overall, 13 qualifying studies including 1030 cases and 561 normal controls were analyzed in this updated meta-analysis. Forest plot of this meta-analysis showed that RA patients had higher circulating sclerostin levels (P < 0.001, standardized mean difference [SMD] = 0.916, 95% CI: 0.235-1.597) compared to normal controls. Subgroup analyses implied that age, region, and assay method were associated with sclerostin level in RA patients., Conclusion: RA patients have higher circulating sclerostin levels, and these was influenced by age, region, and assay method., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Introduction: Paediatric patients with chronic anterior uveitis are more prone to suffer from the chronic course of intraocular inflammation and adverse effects of long-term immunomodulatory therapy, either topical glucocorticosteroids or systemic immunomodulatory agents. The performance of adalimumab has been shown to be fairly favourable in treating refractory non-infectious uveitis, but the detailed indication is still under investigation. This study aims to assess the efficacy and safety of adalimumab for inflammatory flare prevention in non-infectious paediatric anterior uveitis with peripheral retinal vascular leakage, compared with methotrexate., Methods and Analysis: Children weighed ≥30 kg and aged between 4 and 16 years old with active non-infectious anterior uveitis with peripheral retinal vascular leakage on ultra-wildfield fluorescein fundus angiography will be included. They will be treated with a predesigned inflammatory control regimen to reach inflammatory quiescence in 1 month. After that they will be treated with either methotrexate 10 mg once a week or adalimumab once every 2 weeks and regularly followed up for 6 months. The primary endpoint is uveitis flare defined as defined as anterior chamber cell count grading increased from 0 to 1 within the observation period., Ethics and Dissemination: The study was approved by the Institutional Review Board of Peking Union Medical College Hospital, Beijing, China (Approved protocol V3, dated 27 July 2021. Approval number 25-ZS-3062) and has been registered on ClinicalTrials.gov. Written informed consent will be collected from every patient and their guardians prior to study participation. The results of this trial will be presented at local and international meetings and submitted to peer-reviewed journals for publication., Trial Registration Number: NCT05015335., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To explore the therapeutic effect of alternating red and blue light irradiation combined with collagen in patients with acne vulgaris and the risk factors of short-term recurrence., Method: A retrospective analysis was conducted on 105 patients with acne vulgaris treated in Baoji Hospital of Traditional Chinese Medicine from January 2019 to February 2020. 50 patients received conventional treatment (Pumen red and blue light) were taken as the control group, and the other 55 patients treated with collagen dressing on the basis of control group were taken as the research group. Clinical efficacy, changes of serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) before and after treatment, and the occurrence of adverse reactions were compared between the two groups of patients. The scores of inflammatory skin lesions, facial seborrhea scores, stratum corneum water content and transepidermal water loss (TEWL) were compared before and after the treatment. The 1-year review records of patients were queried, and they were divided into a relapse group and a non-relapse group according to the recurrence situation. Logistic regression was used to analyze the risk factors affecting the recurrence of the patients., Results: The clinical efficacy of the patients in research group after treatment was significantly higher than that in the control group (P<0.05). IL-1β and IL-6 in the serum of patients after treatment were markedly decreased, and such decline in the research group was more evident after treatment (P<0.05). The incidence of adverse reactions, the scores of inflammatory skin lesions, and facial seborrhea and TEWL in the research group after treatment were all lower than those in the control group (all P<0.05), while the water content of the stratum corneum was higher comparatively (P<0.05). 17 patients were confirmed with recurrence within 1 year after treatment. Logistic regression analysis found that age, monthly income, pre-treatment IL-1β and pre-treatment IL-6 were risk factors for recurrence., Conclusion: Alternating red and blue light irradiation combined with collagen can improve the treatment efficacy in patients with acne vulgaris. And indexes like age, monthly income, pre-treatment IL-1β and pre-treatment IL-6 are risk factors affecting the recurrence of patients., Competing Interests: None., (AJTR Copyright © 2022.)

Apoptosis is one of the major forms of programmed cell death, and it serves vital biological functions in multicellular animal and plant cells. The core mechanism of apoptosis is highly conserved in metazoans, where the translocation of CED-4/Apaf-1 from mitochondria to the nuclear membrane is required to initiate and execute apoptosis. However, the underlying molecular mechanisms of this translocation are poorly understood. In this study, we showed that SAO-1 binds DLC-1 and prevents its degradation to promote apoptosis in C. elegans germ cells. We demonstrated that SAO-1 and DLC-1 regulate CED-4/Apaf-1 nuclear membrane accumulation during apoptosis. Isothermal titration calorimetry-based assay and high-resolution crystal structure analysis further revealed that SAO-1 interacted with DLC-1 to form a 2:4 complex: each of the two β-sheets in the SAO-1 peptide interacted with two DLC-1 dimers. Point mutations at the SAO-1-DLC-1 binding interface significantly inhibited apoptotic corpse formation and CED-4 nuclear membrane accumulation within C. elegans germ cells. In conclusion, our study provides a new perspective on the regulation of CED-4-mediated apoptosis., (© 2022. The Author(s).)

This is a retrospective study to investigate the impact of inactivated Coronavirus disease-2019 (COVID-19) vaccination on uveitis flare in patients with uveitis. Sixty patients that were regularly followed up for uveitis for at least two months after the last dose of inactivated COVID-19 vaccines were included in the vaccination group. Sixty patients with comparable characteristics of uveitis who had not received the COVID-19 vaccines were included in the control group. Uveitis flare within 30 days and 60 days after the vaccination in the vaccination group, or after a randomly selected date in the control group, were statistically compared. The flare rate was 16.7% (30 days) and 23.3% (60 days) in the vaccination group, while it was 13.3% (30 days) and 25% (15/60) in the control group. There was no statistical difference in the flare rate of uveitis between the two groups ( p = 0.471 for 30 days, p = 0.347 for 60 days). Inactivated COVID-19 vaccination appeared not to increase the flare rate in patients with uveitis. Ophthalmologists should give proper and individualized recommendations based on the overall conditions of patients.

The present study investigated the chemical constituents from the stems of Buddleja lindleyana. Ten compounds were isolated from the 95% EtOH extract of B. lindleyana stems by means of some techniques including polyamide, silica gel, MCI, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography(HPLC). Their structures were identified by spectral analysis and single-crystal X-ray diffraction as buddledin F(1), 6-O-4″-hydroxy-3″-methoxy-benzoyl ajugol(2), negundoin G(3),(+)-dihydrocubebin(4), 7-O-ethylguaiacylglycerol(5),(-)-jatrointelignan B(6), threo-1,2-bis-(4-hydroxy-3-methoxyphenyl)-propane-1,3-diol(7), vomifoliol(8), hinokinin(9), and isovanillic acid(10). Compound 1 was a new sesquiterpene named buddledin F. Compounds 3-8 were isolated from the Buddleja plant for the first time. The anti-inflammatory activities of compounds 1-10 in vitro were investigated, and the results failed to show the inhibitory activities of these compounds on the production of inflammatory factor NO.

The endothelium is the critical barrier that controls transendothelial communications. Blood vessels in cancer tissue are poorly developed and highly permeable. However, it is poorly understood how circulating cancer cells released through these "leaky" vessels break the intact vasculature of remote organs to metastasize. We investigated the roles of cancer cell-derived extracellular vesicles (CEVs) in regulating cancer metastasis by analyzing samples from gastric cancer patients, performing in vitro experiments, and studying mouse models. We made several novel observations. First, the rate of metastasis was closely associated with plasma levels of CEVs in patients with gastric cancer. Second, cultured endothelial cells endocytosed CEVs, resulting in cytoskeletal rearrangement, low expression of the junction proteins cadherin and CD31, and forming large intercellular gaps to allow the transendothelial migration of cancer cells. The dynamin inhibitor Dynasore prevented these CEV-induced changes of endothelial cells by blocking CEVs endocytosis. Third, CEVs disrupted the endothelial barrier of cancer-bearing mice to promote cancer metastasis. Finally, lactadherin promoted the clearance of circulating CEVs to reduce metastasis. These results demonstrate the essential role of CEVs in promoting the metastasis of gastric cancer., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the clinical safety and efficacy of modified CO 2 laser-assisted sclerectomy surgery (CLASS) in patients with uveitic glaucoma (UG) using primary open-angle glaucoma (POAG) patients for a comparison., Methods: This retrospective study included UG and POAG patients from the modified CLASS Study Group database. Intraocular pressure (IOP) and the number of glaucoma medications were compared between groups by the Wilcoxon test. The Kaplan-Meier method was used for survival analysis; complete success was defined as 5≤ IOP≤18 mmHg and a ≥ 20% reduction in IOP from baseline without medication., Results: Twenty-three and 25 eyes in UG and POAG groups were included. At the 12-month visit in both groups, the mean IOP and mean number of IOP-lowering medications were significantly reduced compared to baseline, with complete success rates of 60.9% and 64.0% in the UG and POAG groups ( P = .859)., Conclusions: Modified CLASS yields similar outcomes for patients with UG and POAG.

Aim: To evaluate the effectiveness and corticosteroid-sparing capabilities of methotrexate (MTX) in the treatment of chronic non-necrotizing anterior scleritis in Chinese patients., Methods: A retrospective chart review of all patients with active anterior scleritis between January 2015 and June 2019 was conducted. All patients received 10 to 15 mg/wk MTX orally, and corticosteroids (10 to 40 mg/d prednisolone or equivalent methylprednisolone) with slow tapering. Topical corticosteroid eye drops (1% prednisolone actate, 0.1% dexmathosone or 0.1% fluoromethalone) were applied to control comorbid anterior uveitis at presentation or during follow up. The main outcomes were inflammation control and corticosteroid-sparing success, and secondary outcomes were reduction of immunosuppression load and best-corrected visual acuity (BCVA)., Results: Thirty-two eyes (22 patients) were included. The proportion of patients who achieved corticosteroid-sparing success was 50.0% at 3mo and 77.3% at 12mo [8 (36.4%) patients discontinued corticosteroid]. The proportion of eyes that achieved inflammation control was 59.4% at 3mo and 78.1% at 12mo. The immunosuppression load was 5.14±0.87 at presentation and 2.76±2.34 at 12mo ( P <0.01). BCVA maintained unchanged or improved in 29 (90.6%) of all affected eyes. One patient discontinued MTX treatment because of an abnormal liver function test, and no other serious adverse effects were observed., Conclusion: According to this pilot study, low dose MTX appear to be a well-tolerated and effective treatment for chronic non-necrotizing anterior scleritis patients in the Chinese population., (International Journal of Ophthalmology Press.)

Purpose: To assess the accuracy and robustness of the AI algorithm for detecting referable diabetic retinopathy (RDR), referable macular diseases (RMD), and glaucoma suspect (GCS) from fundus images in community and in-hospital screening scenarios., Methods: We collected two color fundus image datasets, namely, PUMCH (556 images, 166 subjects, and four camera models) and NSDE (534 images, 134 subjects, and two camera models). The AI algorithm generates the screening report after taking fundus images. The images were labeled as RDR, RMD, GCS, or none of the three by 3 licensed ophthalmologists. The resulting labels were treated as "ground truth" and then were used to compare against the AI screening reports to validate the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of the AI algorithm., Results: On the PUMCH dataset, regarding the prediction of RDR, the AI algorithm achieved overall results of 0.950 ± 0.058, 0.963 ± 0.024, and 0.954 ± 0.049 on sensitivity, specificity, and AUC, respectively. For RMD, the overall results are 0.919 ± 0.073, 0.929 ± 0.039, and 0.974 ± 0.009. For GCS, the overall results are 0.950 ± 0.059, 0.946 ± 0.016, and 0.976 ± 0.025., Conclusion: The AI algorithm can work robustly with various fundus camera models and achieve high accuracies for detecting RDR, RMD, and GCS., (Copyright © 2022 Han, Cheng, Zhang, Yang, Yuan, Yang, Wu, Liu, Zhao, Chen and Xu.)

Five new Erythrina alkaloids and five known E. alkaloids were isolated from a 95% ethanol extract of the stems of Erythrina corallodendron L. Their chemical structures were elucidated by UV, IR, HRESIMS, NMR and X-ray. Furthermore, the analgesic activities of E. alkaloids 1 , 2 and 6 were evaluated by using an acetic acid-induced writhing test in mice, and their writhing inhibition rates were 67.9%, 64.6% and 70.3% at doses of 20 mg/kg, respectively.

Retinal vein occlusion (RVO) is one of the most common retinal vascular diseases. The pathogenesis of RVO is multifactorial and involves a complex interplay among a variety of vascular and inflammatory mediators. Many cytokines, chemokines, growth factors, and cell adhesion molecules have been reported to be implicated. Treatments for RVO are directed at the management of underlying risk factors and vision-threatening complications, including macula edema (ME) and neovascularization. Intravitreal anti-VEGF agents are currently considered as the first-line treatment for ME secondary to RVO (RVO-ME), but a substantial proportion of patients responded insufficiently to anti-VEGF agents. Since RVO-ME refractory to anti-VEGF agents generally responds to corticosteroids and its visual outcome is negatively correlated to disease duration, prediction of treatment response at baseline in RVO-ME may significantly improve both cost-effectiveness and visual prognosis. Several bioactive molecules in the aqueous humor were found to be associated with disease status in RVO. This review aims to present a comprehensive review of intraocular biomolecules reported in RVO, including VEGF, IL-6, IL-8, MCP-1, sICAM-1, IL-12, IL-13, sVEGFR-1, sVEGFR-2, PDGF-AA, etc., highlighting their association with disease severity and/or phenotype, and their potential roles in prognostic prediction and treatment selection. Some of these molecules may serve as biomarkers for aqueous humor-based companion diagnostics for the treatment of RVO in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Zhang, Chen, Koh, Zhao and Chen.)

Purpose: This study is aimed to assess the efficacy of adalimumab in alleviating peripheral vascular leakage in pediatric chronic anterior uveitis patients, along with its ability to improve best-corrected visual acuity (BCVA) and inflammation parameters, its efficacy in reducing topical glucocorticosteroids (GCs) and systemic immunomodulatory therapy (IMT), and its safety profile., Methods: A self-controlled study of pediatric chronic anterior uveitis patients who presented with peripheral retinal vascular leakage on ultra-widefield fluorescein fundus angiography and underwent adalimumab treatment was conducted. The primary outcome was the extent of retinal vascular leakage at the 3- and 6-month follow-up visits. Secondary outcomes included BCVA, inflammation parameters (fresh keratic precipitates, anterior chamber cell, and vitreous cell grades), frequency of topical glucocorticosteroid eye drops, IMT load, and adverse effects at the 3- and 6-month follow-up visits., Results: Twenty patients with a mean age of 9.30 ± 3.26 years old were included. The mean follow-up period was 9.0 ± 3.0 months, with all patients followed up for at least 6 months. At the 3- and 6-month follow-ups, the peripheral vascular leakage score decreased significantly (2.87, 95% CI (2.14, 3.60) , p < 0.001 for 3 months, 2.75, 95% CI (1.76, 3.73) , p < 0.001 for 6 months). Alongside BCVA ( p = 0.013 for 3 months, p = 0.005 for 6 months) was improved significantly, inflammatory parameters represented by fresh keratic precipitates, anterior chamber cell, and vitreous cell grades were improved significantly ( p < 0.001, p < 0.001, for all parameters) and topical GC usage was significantly reduced ( p < 0.001, p < 0.001) at 3 and 6 months. There was also a statistically significant reduction in systemic IMT load at 6 months ( p < 0.001). Adverse events in the observation period included local redness around the injection site and mild upper respiratory symptoms., Conclusion: Adalimumab could effectively alleviate peripheral vascular leakage in pediatric patients with chronic anterior uveitis. It could also be helpful in improving BCVA and inflammation parameters and decreasing topical glucocorticosteroid eye drops and systemic IMT. Adalimumab is generally safe for pediatric uveitis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Song, Zhao, Xiao, Gao, Li and Zhang.)

This study compared the efficacy of modified CO 2 laser-assisted sclerectomy surgery (CLASS) with combined CLASS and trabeculectomy (CLASS-TRAB) in patients with uveitic glaucoma (UG). UG patients who underwent CLASS-TRAB between August 2015 and April 2019 were retrospectively compared with a control group who underwent a modified CLASS standalone procedure during the same period. Visual acuity, intraocular pressure (IOP), use of supplemental medical therapy and postoperative complications were recorded at baseline, 1 week, 3 months, 6 months and 12 months. Forty patients (40 eyes) were enrolled, and each group had 20 patients (20 eyes). The age and sex distribution were matched between groups (P > 0.05). Both the preoperative IOP (CLASS: 34.9 ± 9.3 mmHg, CLASS-TRAB: 36.8 ± 8.7 mmHg; P > 0.05) and number of glaucoma medications (CLASS: 3.3 ± 0.4, CLASS-TRAB: 3.5 ± 0.5; P > 0.05) were relatively higher in the CLASS-TRAB group than in the CLASS group. At the final follow-up, the IOP (CLASS: 12.9 ± 3.4 mmHg, CLASS-TRAB: 11.2 ± 2.5 mmHg) and number of glaucoma medications (CLASS: 0.4 ± 0.7 and CLASS-TRAB: 0.2 ± 0.5) significantly decreased in both groups (P < 0.01). Both the complete success rate and qualified success rate were comparable between the two groups (CLASS versus CLASS-TRAB: 55% versus 80%, P = 0.09; 80% versus 95%, P = 0.34). CLASS-TRAB is as efficient as modified CLASS in terms of the IOP-lowering effect, providing a new option for patients with UG that is severe and ineligible for other treatments., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Purpose: To analyze the retinal capillary vascular density (VD) as quantified by optical coherence tomography angiography (OCTA) in patients with pediatric uveitis., Methods: OCTA images of 32 pediatric uveitis patients and 30 normal controls (NC) were obtained retrospectively. The foveal avascular zone (FAZ) area, VDs in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), the central macular thickness (CMT), and subfoveal choroidal thickness (SFCT) were analyzed and compared between active and quiescent uveitic eyes, contralateral eyes and NC eyes., Results: Compared with NCs, the VDs in the SCP and DCP were significantly reduced in eyes with both active and quiescent pediatric uveitis ( P < .05).The SFCT was increased significantly in the active group relative to the quiescent group and NC groups ( P < .05). In contrast, no significant differences were observed in the FAZ and CMT (all P > .05)., Conclusions: Our quantitative OCTA findings suggest that the posterior segment is affected during anterior segment recurrence in patients with pediatric uveitis.

Objective To investigate the suitable services of telemedicine at present and the future from the perspective of medical service supplier,clarify the challenges in the development of telemedicine services at present,and provide evidence-based suggestions for improving the quality of telemedicine services. Methods A questionnaire was developed through literature review for the survey of telemedicine services from the perspective of service providers.From January to June in 2020,electronic questionnaires were collected from volunteers.The data were collated and analyzed by Excel 2010 and SPSS 21.0. Results A total of 614 questionnaires were distributed,and 582 effective questionnaires were collected,which showed an effective rate of 94.79%.The participants of this study were mainly young healthcare workers,including doctors,nurses,technicians,and medical students.Among them,68.73% expressed concern to telemedicine services-related work,and more than 50% only had a basic understanding of the related work.The top five developable telemedicine/healthcare services were health management,online consultation,disease re-examination,disease screening,and difficult disease consultation,which were basically consistent with the services suitable for future development. Conclusions Healthcare workers have a high degree of recognition to the development of telemedicine services,while their understanding of the related technologies remains to be improved.The available telemedicine services focus on online consultation,difficult disease consultation,and disease re-examination,while the complicated medical services need to be improved.In the future,efforts should be made to continuously improve the information construction level and narrow the regional gap of medical services,so as to promote the continuous improvement and the coordinated development of medical services between regions.

Purpose : To analyze quantitative OCT-angiography (OCTA) measurements of Vogt-Koyanagi-Harada (VKH) disease at different disease stages. Methods : OCTA scans of 110 VKH patients in acute uveitic, convalescent and chronic recurrent stage were reviewed; posterior uveitis recurrent cases were excluded. Superficial and deep capillary plexus (SCP and DCP) vascular densities (VD) and subfoveal choroidal thickness (SFCT) were compared. Results : DCP VD was significantly lower and SFCT higher in VKH than normal controls (NC) in all 3 stages (all p < .001). Anterior uveitis recurrent patients had lower SCP and DCP VDs and thicker SFCT than convalescent patients ( p = .001, p < .001, and p = .003, respectively). DCP VD was significantly correlated with visual acuity ( p < .05). Patients with history of anterior recurrence had lower retinal VDs in the convalescent stage than those without ( p < .001). Conclusion : Retinal microcirculation is impaired in VKH. DCP VD might be a sensitive indicator of inflammatory status and appeared to be well associated with visual outcome.

Purpose: Changes of choroidal circulation throughout the disease course of Vogt-Koyanagi-Harada (VKH) disease and the clinical significance remain unclear. Choriocapillary vascular density (CC VD) measured by optical coherence tomography angiography (OCTA) were compared in different disease stages of VKH and its correlation with other parameters was analyzed, aiming to explore their clinical relevance., Methods: This is a retrospective case series. One hundred and fourteen VKH patients and 47 normal controls (NCs) were included. Patients were grouped into the acute uveitic, convalescent, and chronic recurrent stages (only anterior recurrent cases included), and OCTA images were obtained from VKH patients in these stages. Best corrected visual acuity (BCVA), CC VD, and subfoveal choroidal thickness (SFCT) were recorded and compared., Results: CC VD in acute (58.26% ± 0.84%), convalescent (64.85% ± 0.33%), and chronic recurrent (62.78% ± 0.70%) stage of VKH patients were all significantly lower than that in NCs (66.37% ± 0.41%) (p < 0.001, p = 0.017, and p < 0.001, respectively). CC VD increased by 6.59% ± 0.91% with resolution of acute inflammation (p < 0.001) and decreased by 2.07% ± 0.74% during anterior uveitis relapse (p = 0.009). Patients with a positive history of anterior recurrence had lower CC VD (- 2.43% ± 0.75%, p = 0.003) in the convalescent stage than those without. CC VD was negatively correlated with logMAR BCVA in VKH (r =  - 0.261, p < 0.001)., Conclusion: CC VD was decreased in every stage of VKH. CC VD has the potential to reflect the status of uveitis and might be promising in monitoring the disease activity. OCTA is a convenient and straightforward tool to evaluate choroidal vascularity, and CC VD provides supplemental quantitative information of the choriocapillaris. Further studies are needed to explore the values of OCTA quantitative parameters in monitoring VKH progression, predicting visual prognosis, and guiding clinical decisions., (© 2021. The Author(s).)

Objectives: To measure the serum level of IL-33 in patients with Vogt-Koyanagi-Harada disease (VKH) and Behçet's uveitis (BU) in the Chinese Han population and investigate its associations with disease activity and clinical parameters., Methods: Serum was collected from 41 VKH patients (16 active and 25 inactive patients), 60 BU patients (24 active and 36 inactive patients), and 36 healthy controls. The serum level of IL-33 was measured using the enzyme-linked immunosorbent assay (ELISA) method. Demographic features, clinical manifestations, and intraocular inflammation activity scores (anterior chamber cells score, anterior chamber flare score, and vitreal haze score) were recorded., Results: The serum level of IL-33 significantly increased in all VKH patients, active VKH patients, and inactive VKH patients, as compared to healthy controls (p < 0.001, p < 0.001, and p = 0.002, respectively), and was higher in the active VKH than in the inactive VKH patients (p = 0.049). The serum level of IL-33 positively correlated with the anterior chamber cells score, vitreal haze score, and the annualized number of relapses in VKH patients (Rho = 0.359, p = 0.021; Rho = 0.344, p = 0.028; Rho = 0.537, p < 0.001, respectively). Serum IL-33 level was significantly associated with the annualized number of relapses in patients with BU (Rho = 0.361, p = 0.005)., Conclusion: Serum IL-33 level is significantly increased in VKH patients in the Chinese Han population. IL-33 level is in positive correlation with the activity and relapses of VKH. Increased IL-33 might contribute to the pathogenesis of VKH and serve as a potential biomarker for VKH disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aim: To explore the association of single nucleotide polymorphisms (SNPs) in the IL33/IL1RL1 gene region with the susceptibility to Behcet's disease (BD) in a Chinese Han population., Methods: A total of eight SNPs in the candidate gene region (rs11792633, rs7025417, rs10975519 and rs1048274 in IL33 ; rs2310220, rs12712142, rs13424006 and rs3821204 in IL1RL1 ) were genotyped in783 BD patients and 701 healthy controls by the Sequenom Mass Array iPLEX platform., Results: A statistically significant association was observed between IL1RL1 rs12712142 and BD patients. The frequency of IL1RL1 rs12712142 variant allele A was significantly lower in BD patients than that in controls (OR=0.8, 95%CI: 0.69-0.94, Pc =0.039); the genotype distribution ( Pc =0.043) and additive and dominant genetic model analyses (OR=0.8, 95%CI: 0.69-0.94, Pc =0.040 and OR=0.72, 95%CI: 0.58-0.88, Pc =0.011) also indicated a strong association between rs12712142 and BD patients., Conclusion: This is the first study to reveal the association between IL1RL1 rs12712142 variant allele A and the decreased risk of BD in the Chinese Han population, indicating a protective role of IL1RL1 in the pathogenesis of BD., (International Journal of Ophthalmology Press.)

Purpose: To investigate choroidal changes in patients with Vogt-Koyanagi-Harada disease (VKH) using widefield swept-source optical coherence tomography angiography (SS-OCTA). Methods: In this cross-sectional study, 133 eyes of 69 patients with VKH (52 eyes of 28 active VKH patients and 81 eyes of 41 inactive VKH patients) and 104 eyes of 52 age and sex matched healthy volunteers were imaged using a widefield SS-OCTA instrument. On 12 mm × 12 mm OCTA scans, mean choroidal thickness (MCT), choroidal vascularity index (CVI), choriocapillaris (CC) flow area, and mean retinal thickness (MRT) were separately calculated in the fovea (diameter of 1 mm) and in concentric rings with different radii (1-3, 3-6, 6-9, and 9-12 mm). Results: Eyes with active VKH showed significant increases in MCT, CVI, and MRT, and decreased CC flow area in all central and peripheral regions (0-1, 1-3, 3-6, 6-9, and 9-12 mm) than in the healthy eyes ( p ≤ 0.01) and inactive VKH eyes ( p < 0.05). Inactive VKH eyes only showed marked decrease in CC flow area in all regions compared with controls ( p < 0.05). Flow voids were observed in 51 of 52 (98.1%) active VKH eyes and 50 of 81 (61.7%) inactive VKH eyes on 12 mm × 12 mm OCTA. The MCT of all regions was significantly correlated with age, disease duration, and disease activity, whereas CVI was associated with age and disease activity. The CC flow void was related to visual acuity in all regions ( p < 0.05). Conclusion: Widefield SS-OCTA enables a more comprehensive evaluation of chorioretinal changes in patients with VKH disease. Structural and vascular abnormalities are observed in both the central and peripheral choroid and are closely correlated with disease activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qian, Yang, Liang, Zhao, Gao and Zhang.)