Targeted lipidomics uncovers oxylipin perturbations and potential circulation biomarkers in Bietti's crystalline dystrophy.

PURPOSE: Abnormalities in lipid metabolism have been proposed in Bietti's crystalline dystrophy (BCD). We aim to characterize the lipid profiles in a case-control study. METHODS: All participants were genetically confirmed by CYP4V2 gene sequencing and underwent chorioretinopathy evaluation by calculating the percentages of AF atrophy (PAFA). Fasting blood samples of BCD patients and controls were collected, and plasma was analyzed for routine lipid profiles. Targeted lipidomic evaluation includes long chain polyunsaturated fatty acids (LCPUFA) and associated eicosanoid metabolites. RESULTS: Routine lipids profiles showed elevated plasma levels of triglyceride (P = 0.043) and low-density lipoprotein cholesterol (P = 0.024) in BCD patients. Lipidomic analysis showed significantly decreased levels of ω-3 LCPUFA including docosahexaenoic acid (DHA, 22:6, P = 0.00068) and eicosapentaenoic acid (EPA, 20:5, P = 0.0016), as well as ω-6 LCPUFA arachidonic acid (ARA, 20:4, P < 0.0001) in BCD patients. Eicosanoid metabolites, either derived from ω-3 and/ or ω-6 LCPUFAs via cyclooxygenase (COX) or lipoxygenase (LOX) pathways, including 5-HEPE, 12-HEPE, 13-HDHA, 15-HETE, 12-HETE, 5-HETE, 6k-PGF1a, PGE2, PGJ2, and TXB2, exhibited significant differences (P < 0.0001) between BCD patients and controls. Genotypes of CYP4V2, specifically the biallelic null mutations, were observed to correlate with more remarkably reduced levels of oxylipins, involving major LOX pathway metabolites including 5-HETE, 5-HEPE, 12-HEPE and LTB4. CONCLUSIONS: BCD patients demonstrated significant decreases in plasma levels of ω-3 and ω-6 LCPUFA (DHA, EPA, and ARA), as well as their downstream metabolites via the COX and LOX pathways, suggesting that these might be implicated in BCD pathogenesis and could serve as biomarkers and therapeutic targets of the disease. KEY MESSAGES: What is known BCD is a vision-threatening hereditary disease the causative gene of which is CYP4V2. Abnormalities in lipid metabolism have been proposed and demonstrated previously in BCD studies. The detailed pathogenesis remains unclear and controversial. What is new We observed prominent lipidomic alterations in the circulation when compared with age, gender, and bodymass index (BMI)-matched healthy controls. BCD patients demonstrated significant decreases in plasma levels of ω-3 and ω-6 LCPUFA (DHA, EPA, and ARA). Remarkable changes were observed in the downstream metabolites of the LCPUFA via the COX and LOX pathways. Genotypes of CYP4V2, specifically the biallelic null mutations, were observed to correlate with more remarkably reduced levels of oxylipins, involving major LOX pathway metabolites.

Urban environmental monitoring and health risk assessment introducing a fuzzy intelligent computing model.

Introduction: To enhance the precision of evaluating the impact of urban environments on resident health, this study introduces a novel fuzzy intelligent computing model designed to address health risk concerns using multi-media environmental monitoring data. Methods: Three cities were selected for the study: Beijing (B City), Kunming (K City), and Wuxi (W City), representing high, low, and moderate pollution levels, respectively. The study employs a Fuzzy Inference System (FIS) as the chosen fuzzy intelligent computing model, synthesizing multi-media environmental monitoring data for the purpose of urban health risk assessment. Results: (1) The model reliably estimates health risks across diverse cities and environmental conditions. (2) There is a positive correlation between PM2.5 concentrations and health risks, though the impact of noise levels varies by city. In cities B, K, and W, the respective correlation coefficients are 0.65, 0.55, and 0.7. (3) The Root Mean Square Error (RMSE) values for cities B, K, and W, are 0.0132, 0.0125, and 0.0118, respectively, indicating that the model has high accuracy. The R2 values for the three cities are 0.8963, 0.9127, and 0.9254, respectively, demonstrating the model's high explanatory power. The residual values for the three cities are 0.0087, 0.0075, and 0.0069, respectively, indicating small residuals and demonstrating robustness and adaptability. (4) The model's p-values for the Indoor Air Quality Index (IAQI), Thermal Comfort Index (TCI), and Noise Pollution Index (NPI) all satisfy p < 0.05 for the three cities, affirming the model's credibility in estimating health risks under varied urban environments. Discussion: These results showcase the model's ability to adapt to diverse geographical conditions and aid in the accurate assessment of existing risks in urban settings. This study significantly advances environmental health risk assessment by integrating multidimensional data, enhancing the formulation of comprehensive environmental protection and health management strategies, and providing scientific support for sustainable urban planning.

Utilizing support vector machines to foster sustainable development and innovation in the clean energy sector via green finance.

As the global demand for clean energy continues to grow, the sustainable development of clean energy projects has become an important topic of research. in order to optimize the performance and sustainability of clean energy projects, this work explores the environmental and economic benefits of the clean energy industry. through the use of Support Vector Machine (SVM) Multi-factor models and a bi-level multi-objective approach, this work conducts comprehensive assessment and optimization. with wind power base a as a case study, the work describes the material consumption of wind turbines, transportation energy consumption and carbon dioxide (CO2) emissions, and infrastructure material consumption through descriptive statistics. Moreover, this work analyzes the characteristics of different wind turbine models in depth. On one hand, the SVM multi-factor model is used to predict and assess the profitability of Wind Power Base A. On the other hand, a bi-level multi-objective approach is applied to optimize the number of units, internal rate of return within the project, and annual average equivalent utilization hours of the Wind Power Base A. The research results indicate that in March, the WilderHill New Energy Global Innovation Index (NEX) was 0.91053, while the predicted value of the SVM multi-factor model was 0.98596. The predicted value is slightly higher than the actual value, demonstrating the model's good grasp of future returns. The cumulative rate of return of Wind Power Base A is 18.83%, with an annualized return of 9.47%, exceeding the market performance by 1.68%. Under the optimization of the bi-level multi-objective approach, the number of units at Wind Power Base A decreases from the original 7004 to 5860, with total purchase and transportation costs remaining basically unchanged. The internal rate of return of the project increases from 8% to 9.3%, and the annual equivalent utilization hours increase to 2044 h, comprehensively improving the investment return and utilization efficiency of the wind power base. Through optimization, significant improvements are achieved in terAs the global demand for clean energy continues to grow, the sustainable development of clean energy projects has become an important topic of research. In order to optimize the performance and sustainability of clean energy projects, this work explores the environmental and economic benefits of the clean energy industry. Through the use of Support Vector Machine (SVM) multi-factor models and a bi-level multi-objective approach, this work conducts comprehensive assessment and optimization. With Wind Power Base A as a case study, the work describes the material consumption of wind turbines, transportation energy consumption and carbon dioxide (CO2) emissions, and infrastructure material consumption through descriptive statistics. Moreover, this work analyzes the characteristics of different wind turbine models in depth. On one hand, the SVM multi-factor model is used to predict and assess the profitability of Wind Power Base A. On the other hand, a bi-level multi-objective approach is applied to optimize the number of units, internal rate of return within the project, and annual average equivalent utilization hours of the Wind Power Base A. The research results indicate that in March, the WilderHill New Energy Global Innovation Index (NEX) was 0.91053, while the predicted value of the SVM multi-factor model was 0.98596. The predicted value is slightly higher than the actual value, demonstrating the model's good grasp of future returns. The cumulative rate of return of Wind Power Base A is 18.83%, with an annualized return of 9.47%, exceeding the market performance by 1.68%. Under the optimization of the bi-level multi-objective approach, the number of units at Wind Power Base A decreases from the original 7004 to 5860, with total purchase and transportation costs remaining basically unchanged. The internal rate of return of the project increases from 8% to 9.3%, and the annual equivalent utilization hours increase to 2044 h, comprehensively improving the investment return and utilization efficiency of the wind power base. Through optimization, significant improvements are achieved in terms of the number of units, internal rate of return within the project, and annual average equivalent utilization hours at Wind Power Base A. The number of units decreases to 5860, with total purchase and transportation costs remaining basically unchanged, the internal rate of return increases to 9.3%, and annual equivalent utilization hours increase to 2044 h. Energy consumption and CO2 emissions are significantly reduced, with energy consumption decreasing by 0.68 × 109 kgce and CO2 emissions decreasing by 1.29 × 109 kg. The optimization effects are mainly concentrated in the production and installation stages, with emission reductions achieved through the recycling and disposal of materials consumed in the early stages. In terms of investment benefits, environmental benefits are enhanced, with a 13.93% reduction in CO2 emissions. Moreover, there is improved energy efficiency, with the energy input-output ratio increasing from 7.73 to 9.31. This indicates that the Wind Power Base A project has significant environmental and energy efficiency advantages in the clean energy industry. This work innovatively provides a comprehensive assessment and optimization scheme for clean energy projects and predicts the profitability of Wind Power Base A using SVM multi-factor models. Besides, this work optimizes key parameters of the project using a bi-level multi-objective approach, thus comprehensively improving the investment return and utilization efficiency of the wind power base. This work provides innovative methods and strong data support for the development of the clean energy industry, which is of great significance for promoting sustainable development under the backdrop of green finance.

Clinical features and possible pathogenesis of multiple evanescent white dot syndrome with different retinal diseases and events: a narrative review.

Multiple evanescent white dot syndrome (MEWDS) is a rare fundus disease, characterized by acute vision loss and visual field defects. Many previous studies have explained the possible pathogenesis and clinical features of primary MEWDS. However, as the number of reported cases increases, secondary MEWDS occurs in other related retinal diseases and injuries, exhibiting some special characteristics. The associated retinal diseases include multifocal choroiditis/punctate inner choroidopathy (MFC/PIC), acute zonal occult outer retinopathy, best vitelliform macular dystrophy, pseudoxanthoma elasticum, and ocular toxoplasmosis. The related retinal injury is laser photocoagulation, surgery, and trauma. Although primary MEWDS often have a self-limiting course, secondary MEWDS may require treatment in some cases, according to the severity of concomitant diseases and complications. Notably, MEWDS secondary to MFC/PIC that is prone to forming choroidal neovascularization and focal choroidal excavation, needs positive treatment with corticosteroids. The possible underlying pathogenesis of secondary MEWDS is the exposure of choroidal antigen after the disruption of Bruch's membrane. The MEWDS-related features in secondary MEWDS are still evanescent under most circumstances. Its prognosis and treatment depend on the severity of complications. Current studies propose that the etiology is associated with immune factors, including viral infection, inflammation in choroid and Bruch's membrane, and antigen exposure caused by retinal and/or choroidal insults. More pathogenic studies should be conducted in the future. Accurate diagnosis for secondary MEWDS could benefit patients in aspects of management and prognosis.

Betaine addition to the diet alleviates intestinal injury in growing rabbits during the summer heat through the AAT/mTOR pathway.

BACKGROUND: The aim of this experiment was to investigate the effect of different levels of betaine (Bet) inclusion in the diet on the intestinal health of growing rabbits under summer heat. A total of 100 weaned Qixing meat rabbits aged 35 d with body weight of 748.61 ± 38.59 g were randomly divided into 5 treatment groups: control group (basal diet) and Bet groups (basal diet + 0.75, 1.0, 1.5 or 2.0 g/kg Bet). The average daily temperature in the rabbitry during the experiment was 30.48 °C and the relative humidity was 69.44%. RESULTS: Dietary addition of Bet had no significant effect on growth performance and health status of growing rabbits (P > 0.05), but it increased ileal secretory immunoglobulin A content compared to the control under summer heat (P < 0.05). Addition of 0.75 g/kg Bet up-regulated jejunal IL-4, down-regulated ileal TNF-α expression (P < 0.05). The addition of 1.0 g/kg Bet increased the villi height (VH) in the jejunum (P < 0.05). Serum glucose levels were reduced, and the expression of SLC6A20 was up-regulated in jejunum and ileum of rabbits fed with 1.5 g/kg Bet (P < 0.05). When added at 2.0 g/kg, Bet reduced serum HSP70 content, increased jejunal VH, and up-regulated duodenal SLC7A6, SLC38A2, mTOR and 4EBP-2 expression (P < 0.05). Correlation analysis revealed that intestinal mTOR expression was significantly and positively correlated with SLC7A6, SLC38A2, SLC36A1 and IL-4 expression (P < 0.05). CONCLUSIONS: Dietary addition of Bet can up-regulate the expression of anti-inflammatory factors through the AAT/mTOR pathway, improve the intestinal immune function, alleviate intestinal damage in growing rabbits caused by summer heat, and improve intestinal health.

Analysis of factors related to the development of ocular biometric parameters in Chinese children aged 6-10 years: a cross-sectional study.

OBJECTIVES: Emmetropia depends on the precise coordination of ocular biometry, including axial length (AL), corneal curvature, lens thickness and anterior chamber depth (ACD). Disruption of this coordination leads to refractive errors such as myopia. This article aimed to determine the factors affecting ocular biometry and myopia development in young children. DESIGN: A cross-sectional study. SETTING: This study was conducted in a primary school in the Yanqing district of Beijing, China. PARTICIPANTS: 792 students in grades 1-3 without hyperopia (>+2.00 D), strabismus, or amblyopia were selected. EXCLUSIONS: students had conditions affecting best corrected visual acuity and whose guardians refused to provide informed consent. Ocular biometric measurements and non-cycloplegia autorefraction were performed. The questionnaire addressed factors such as perinatal factors and environmental factors. INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOMES: Ocular biometry and myopia. RESULTS: According to the multivariate logistic regression analysis, electronic screen use >2 hours/day (OR=2.175, p=0.013), paternal myopia (OR=1.761, p=0.002), maternal myopia (OR=1.718, p=0.005), taller height (OR=1.071, p<0.001), maternal education (OR=0.631, p=0.012) and maternal gestational hypertension (OR=0.330, p=0.042) were associated with myopia. AL was affected by female sex (OR=0.295, p<0.001), older age (OR=1.272, p=0.002) and taller height (OR=1.045, p<0.001). Female sex (OR=0.509, p<0.001), taller height (OR=1.046, p<0.001), use of electronic screens >2 hours each day (OR=3.596, p<0.001) and time spent outdoors >2 hours each day (OR=0.431, p=0.001) influenced ACD incidence. Central corneal thickness (CCT) was associated with older age (OR=1.113, p=0.008), paternal education (OR=1.474, p=0.007), premature birth (OR=0.494, p=0.031), history of blue light therapy in infancy (OR=0.636, p=0.041) and history of incubator therapy in infancy (OR=0.263, p=0.009). Only sex influenced corneal curvature. CONCLUSIONS: The factors associated with myopia were partly related to ACD and AL, and perinatal factors were associated with myopia and CCT. TRIAL REGISTRATION NUMBER: ChiCTR2200065398.

Effect of topical 5-aminolevulinic acid-mediated photodynamic therapy combined with CO2 laser pretreatment for vaginal condyloma acuminate.

BACKGROUND: Condyloma acuminatum (CA) of the vagina is a sexually transmitted disease due to infection by human papilloma virus (HPV). The treatment efficacy of the conventional methods for vaginal CA is often unsatisfactory with a high recurrence rate. Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) combined with CO2 laser pretreatment is a feasible approach for vaginal CA, but the effectiveness and safety need further evaluation. METHODS: This study enrolled 15 patients with vaginal CA. All patients underwent CO2 laser ablation and then ALA-PDT for two or three cycles. The clinical efficacy and side effects were evaluated and analyzed during the treatment and 6 months after the treatment. RESULTS: The wart lesions in 4 cases (26.7 %) disappeared after the first treatment. The wart lesions in 5 cases (33.3 %) disappeared after the second treatment. And 6 cases (40 %) needed three treatment cycles before the lesions disappeared completely. The complete response (CR) rate was 93.3 % (14/15) at 2 weeks after three treatment cycles. There were 5 cases (83.3 %) which have complete remission after 2 treatments in warts diameter <1 cm group. There were only 4 cases (44.4 %) which have complete remission after 2 treatments in diameter>1 cm group. All patients had CR without reoccurrence at 6 months after treatment. The side effects mainly included a mild or moderate burning or stinging sensation (26.7 %). There were no infection, ulcers and scars after treatment. CONCLUSION: Topical 5-aminolevulinic acid-mediated photodynamic therapy combined with CO2 laser pretreatment is a safe and effective treatment for vaginal CA.

Unilateral Acute Retinal Necrosis with Contralateral Non-necrotizing Herpetic Uveitis.

PURPOSE: The objective of this study is to report a case of unilateral acute retinal necrosis (ARN) with contralateral eye presenting as non-necrotizing herpetic uveitis. CASE REPORTS: Case 1: A 48-year-old female presented at our clinic with blurred vision in the right eye for 7 days. She was diagnosed with ARN in the left eye 2 weeks ago. Ophthalmic examination revealed reduced visual acuity in the right eye (20/33) with the presence of optic disc swelling and macular exudation without peripheral necrotic lesions. With systemic antiviral therapy, optic disc swelling of the right eye vanished gradually, and the visual acuity improved to 20/20. Loss of retinal nerve fiber layer (RNFL) and decreased retinal thickness in the corresponding area occurred during follow-up. CONCLUSION: Non-necrotizing herpetic uveitis may occur in the contralateral eye of unilateral ARN under rare conditions. Structure abnormities, including loss of RNFL and focal decreased retinal thickness, are irretrievable.

The multimodal imaging features and outcomes of multifocal choroiditis/punctate inner choroidopathy lesion with multiple evanescent white dot syndrome-like features: a retrospective study.

BACKGROUND: Multiple evanescent white dot syndrome (MEWDS)-like features is a rare condition triggered by a macular disease or iatrogenic injury, exhibiting MEWDS changes in the fundus. This study aims to describe the multimodal imaging features and outcomes of multifocal choroiditis/punctate inner choroidopathy (MFC/PIC) lesions with MEWDS-like features. METHODS: Six cases were studied retrospectively. All cases were given regional and oral corticosteroids. RESULTS: All cases showed an isolated juxtafoveal yellowish-white MFC/PIC lesion with disruption of RPE-Bruch's membrane-choriocapillaris complex (RPE-BM-CC), subretinal hyperreflective materials and choroidal thickening on optical coherence tomography. Two weeks after presentation, the grayish-white dots disappeared spontaneously and the corticosteroids were given. After four weeks, the ellipsoid zone (EZ) around the lesion and hyper-autofluorescence resolved. After 13 weeks, five cases showed shrinkage of the juxtafoveal lesion and restoration of foveal EZ. After six months, the juxtafoveal lesion became pigmented. Only one case developed type 2 choroidal neovascularization. CONCLUSIONS: The clinical course of MEWDS-like manifestations is still evanescent in our cases. The yellowish-white juxtafoveal MFC/PIC lesions with disruption of RPE-BM-CC and choroidal thickening showed a well-controlled prognosis after corticosteroid treatment.

Nitrate budget of a terrestrial-to-marine continuum in South China: Insights from isotopes and a Markov chain Monte Carlo model.

Anthropogenic nitrate (NO3-) production has been increasing and is exported to the ocean via river networks, causing eutrophication and ecological damage. While studies have focused on river NO3- pollution, what has been lacking is the quantification of the sources of NO3- in coastal rivers. This study applied the dual isotopes (δ15N/δ18O-NO3-) to quantify the sources and their fluxes of NO3- in two inflow rivers of the Qinzhou Bay. By adding our results to the NO3- source apportionment in Qinzhou Bay, we, for the first time, established the NO3- budgets of the terrestrial-to-marine continuum in both high- and low-flow seasons. We quantitatively showed the direct and indirect roles (e.g., the stimulation of nitrification by sewage ammonium-NH4+) of terrestrial sources in driving the high NO3- loading in the estuary. The results highlighted the necessity to consider coastal rivers and estuary as a whole, which could shed light on the effective reduction of NO3- pollution in coastal environments.

Long-Term Indomethacin Treatment in a Chinese Child with Gitelman Syndrome: Case Report and Literature Review on its Efficacy and Tolerance.

BACKGROUND Gitelman syndrome (GS) is a rare inherited autosomal recessive salt-losing renal tubulopathy. Early-onset GS is difficult to differentiate from Bartter syndrome (BS). It has been reported in some cases that cyclooxygenase (COX) inhibitors, which pharmacologically reduce prostaglandin E2(PGE2) synthesis, are helpful for GS patients, especially in children, but the long-term therapeutic effect has not yet been revealed. CASE REPORT A 4-year-old boy was first brought to our hospital for the chief concern of short stature and growth retardation. Biochemical tests demonstrated severe hypokalemia, hyponatremia, and hypochloremic metabolic alkalosis. The patient's serum magnesium was normal. He was diagnosed with BS and treated with potassium supplementation and indomethacin and achieved stable serum potassium levels and slow catch-up growth. At 11.8 years of age, the patient showed hypomagnesemia and a genetic test confirmed that he had GS with compound heterozygous mutations in the SLC12A3 gene. At the age of 14.8 years, when indomethacin had been taken for nearly 10 years, the boy reported having chronic stomachache, while his renal function remained normal. After proton pump inhibitor and acid inhibitor therapy, the patient's symptoms were ameliorated, and he continued to take a low dose of indomethacin (37.5 mg/d divided tid) with good tolerance. CONCLUSIONS Early-onset GS in childhood can be initially misdiagnosed as BS, and gene detection can confirm the final diagnosis. COX inhibitors, such as indomethacin, might be tolerated by pediatric patients, and long-term therapy can improve the hypokalemia and growth retardation without significant adverse effects.

Vitreoretinal Lymphoma with Intraretinal Infiltration, Simulating Retinal Necrosis.

PURPOSE: To describe the clinical features and outcomes of vitreoretinal lymphoma (VRL) with intraretinal infiltration, a pseudonecrotic variant. DESIGN: Retrospective, comparative analysis. SUBJECTS: Patients with biopsy-proven VRL at a single center from August 2016 to April 2022. METHODS: A retrospective record review was conducted for clinical, imaging, and laboratory data. MAIN OUTCOME MEASURES: Clinical features, visual, and survival outcomes. RESULTS: We included 67 eyes of 40 patients with biopsy-proven VRL. Pseudonecrotic retinal lesions (PRLs) were found in 24 (35.8%) eyes of 19 patients; these eyes were classified as a pseudonecrotic variant, whereas the remaining 43 (64.2%) eyes were classified as nonnecrotic. Comparison (pseudonecrotic vs. nonnecrotic) revealed that eyes with PRLs at presentation had a worse median best-corrected visual acuity (BCVA; 2.4 vs. 0.5 logarithm of the minimum angle of resolution [logMAR], P < 0.0001) and severe ocular manifestations (P < 0.0001), including optic disc swelling (79.2% vs. 0%), retinal vasculitis (93.8% vs. 4.7%), retinal hemorrhage (83.3% vs. 0%), and retinal detachment (RD) (79.2% vs. 0%). Follow-up data were available for 20 eyes (17 patients) in the pseudonecrotic group and 43 eyes (21 patients) in the nonnecrotic group. An equally worse median BCVA was noted in pseudonecrotic eyes at 6 months after treatment and the final follow-up as compared with nonnecrotic eyes (2.4 vs. 0.3 logMAR, P < 0.0001). The median follow-up period did not differ significantly (16.6 vs. 18.4 months, P = 0.47). Initial BCVA (ß = 0.300, P = 0.003), presence of anterior chamber cell (ß = 0.472, P = 0.013), and RD (ß = 1.137, P < 0.0001) were significantly associated with poor visual outcomes in multivariate linear regression analysis (adjusted R2 = 0.693). There were no significant differences in survival outcomes. CONCLUSION: Vitreoretinal lymphoma can present as pseudonecrotic retinopathy, with more advanced clinical presentations and worse final visual outcomes. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Efficacy and safety of first-line combination therapy versus monotherapy for vitreoretinal lymphoma: a systematic review and meta-analysis.

BACKGROUND: Vitreoretinal lymphoma (VRL) is usually treated with a combination of intraocular methotrexate (ioMTX), high-dose intravenous methotrexate (HD-MTX), or local radiotherapy (RT) as the first options. The effectiveness and safety of monotherapy like bruton's tyrosine kinase inhibitors (BTKi) for PVRL remain uncertain. METHODS: A systematic review and meta-analysis of clinical trial data and conference abstracts in VRL patients treated with first-line combination therapy or monotherapy were conducted through a search of PubMed, Embase, and Scopus databases until December 2022. A total of 24 studies comprising 517 patients were included, and survival data were extracted from 279 patients due to inconsistent units across studies. RESULTS: The combined treatment group used ioMTX + chemotherapy (in 4 studies), RT + chemotherapy (in 2 studies), ioMTX/HD-MTX based regimen (in 2 studies), ioMTX + RT + chemotherapy (in 2 studies), ioMTX + lenalidomide/BTKi (in 2 studies) and combination of multiple therapies (in 7 studies). The monotherapy group was mainly treated with oral monotherapies such as BTKi. The combination therapy had a higher overall response rate (ORR) and complete response rate (CRR) than monotherapy (ORR: 96% vs. 72%, CRR: 92% vs. 63%). Combination therapy also resulted in a longer median progression-free survival (28.8 months vs. 13 months, p = 0.012). However, the combination therapy group had more severe side effects (grade 3/4 toxicity) than the monotherapy group (45% vs. 8%). CONCLUSION: The study showed combination therapy had better OR and CR rates, longer survival, and more toxicity than monotherapy. While BTK inhibitors were well-tolerated, long-term effectiveness needs confirmation from prospective studies. In addition, given the small number of studies of monotherapy for VRL, more studies are needed to validate its effects. TRIAL REGISTRATION: CRD42023400305.

Bietti's crystalline dystrophy: genotyping and deep qualitative and quantitative phenotyping in preparation for clinical trials.

PURPOSE: To qualitatively and quantitatively characterise the genotypes and phenotypes of Bietti's crystalline dystrophy (BCD) in a cohort of patients. DESIGN: Cross-sectional and observational study. METHODS: Clinically confirmed BCD patients were recruited for genotyping and phenotyping. Multiple retinal imaging modalities were employed. Atrophy in the fovea was adopted as major consideration for staging strategy, while percentage area of autofluorescence (AF) atrophy (PAFA) in the macula was determined for quantitation. RESULTS: In 74 clinically diagnosed BCD patients, c.802-8_810del17insGC was shown the predominant variant of the CYP4V2 gene (allele frequency 55.4%). Sixty-two cases (123 eyes) with full imaging data were classified according to a modified criterion into stages 1 (n=8, 6.50%), 2A (n=9, 7.32%), 2B (n=17, 13.82%), 3A (n=30, 24.39%) and 3B (n=59, 47.97%). The eyes of the stage 2B were particularly deemed 'high risk' due to atrophy near fovea, while in stage 3A, though with remarkable foveal atrophy, preserved retinal pigment epithelium/photoreceptor islands near the fovea were found in 14 eyes. A tendency of increase in PAFA with age was found (rs=0.31, p=0.014). Significant PAFA increase was shown through stages 1 to 3B, and best-corrected visual acuity (BCVA, Logarithm of the Minimum Angle of Resolution) was shown to moderately correlate with PAFA (rs=0.56, p<0.001). CONCLUSION: The PAFA might be an efficient biomarker for BCD severities correlating with BCVA. The highly heterogeneous chorioretinopathy and BCVA of BCD cases appear to be associated with disease stages, progression types and patients' ages. Foveal involvement should be of a major concern for consideration of potential therapeutic intervention.

Attitudes and intentions toward seeking professional psychological help among Chinese healthcare workers during the COVID-19 pandemic.

Background: It has been suggested that healthcare workers (HCWs) are experiencing massive stressors that threaten their mental health during the COVID-19 pandemic, but little is known about their attitudes and intentions toward seeking professional psychological help. This study aimed to investigate the attitudes and intentions of Chinese HCWs toward seeking professional psychological help during the COVID-19 pandemic and the associated factors. Methods: A total of 1,224 Chinese HCWs working in hospitals were recruited online from 12 hospitals in Hunan province in China for a survey conducted in November 2022. The Chinese version of the attitudes toward seeking professional psychological help scale-short form (ATSPPH-SF) and the general help-seeking questionnaire (GHSQ) were separately used to assess the attitudes and intentions of the respondents toward seeking professional psychological help. Demographic and socio-psychological data were collected using a self-developed questionnaire, the perceived social support scale, the self-stigma of seeking help scale, and the patient health questionnaire-9 scale. Results: The 1,208 HCWs in the final analysis showed relatively negative attitudes and low intentions toward seeking professional psychological help during the COVID-19 pandemic. Results of the multiple linear regression analysis showed that female sex (p = 0.031), experience of psychological learning (p < 0.001), and social support (p < 0.001) had a positive predictive effect on the attitudes of these HCWs toward seeking professional psychological help, whereas self-stigma of seeking help (p < 0.001) and depressive symptoms (p < 0.001) exerted negative effects. Moreover, experience of psychological learning (p = 0.004) and social support (p < 0.001) had a positive predictive effect on the intentions of these HCWs toward seeking professional psychological help, whereas divorced marital status (p = 0.011) and self-stigma of seeking help (p < 0.001) exerted negative effects. Conclusion: The overall attitudes and intentions of HCWs toward seeking professional psychological help were not optimistic. Effective interventions targeted at influencing factors should be formulated to promote the professional psychological help-seeking attitudes and intentions of HCWs who are at risk of developing mental health problems.

Comprehensive Genetic Analysis Unraveled the Missing Heritability and a Founder Variant of BEST1 in a Chinese Cohort With Autosomal Recessive Bestrophinopathy.

Purpose: To describe the genetic landscape of BEST1 for a large Chinese cohort with autosomal recessive bestrophinopathy (ARB), identify the missing heritability, and report a common Chinese founder variant. Methods: We recruited 65 patients from 63 families with a clinical diagnosis of ARB. All patients underwent ophthalmic examinations and comprehensive genetic analyses, including Sanger DNA sequencing of BEST1 and whole genome sequencing (WGS). The effects of deep intronic variants (DIVs) on splicing were assessed using in vitro splicing assays in HEK293T cells and patient-derived peripheral blood mononuclear cells. Haplotype mapping was performed for 17 unrelated patients harboring variant c.867+97G>A. Results: We identified 54 distinct disease-causing variants of BEST1 in 63 pedigrees, 62 probands with biallelic variants, and one family with monoallelic variants. Sanger DNA sequencing of BEST1 initially detected 51 variants in 61 pedigrees, including 19 probands with one heterozygous variant. Subsequent WGS, combined with supplementary Sanger sequencing, revealed three missing DIVs (c.1101-491A>G, c.867+97G>A, and c.867+97G>T) in 20 families. The novel DIV c.1101-491A>G caused an abnormal splicing resulting in a 204-nt pseudoexon (PE) insertion, whereas c.867+97G>A/T relatively strengthened an alternative donor site, resulting in a 203-nt intron retention (IR). The PE and IR generated a premature termination codon downstream. Haplotype analysis identified c.867+97G>A as a common founder variant with an allele frequency of 16%. Conclusions: Our results expand the pathogenic variant spectrum of BEST1, and DIVs can explain almost all of the missing heritability. The c.867+97G>A DIV is a common founder variant for Chinese patients with ARB.

Analysis of influencing factors of anxiety and depression in maintenance hemodialysis patients and its correlation with BDNF, NT-3 and 5-HT levels.

Objective: The aim of this study is to examine the factors that contribute to anxiety and depression in individuals undergoing maintenance hemodialysis (MHD), as well as their association with serum levels of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and serotonin (5-HT). Methods: In May 2020 and June 2022, 120 MHD patients who received MDH treatment at our hospital were enrolled. The control group was composed of 60 healthy adults (>18) who completed the physical examination at the same time. The serum levels of BDNF, NT-3, and 5-HT in patients and clinical data of MHD patients with different degrees of anxiety and depression were compared. The Pearson correlation was used to evaluate the correlation between anxiety and depression scores and serum BDNF, NT-3,5-HT levels in patients with MHD. Multivariate analysis was employed to analyze the risk factors of anxiety and depression in MHD patients. Results: The incidence of anxiety and depression in 120 MHD patients was 34.17% (41/120) and 64.17% (77/120), respectively. The levels of serum NT-3 and 5-HT in the anxiety group were higher than those in the non-anxiety and control group, and the levels of serum NT-3 in the non-anxiety group were higher than those in the control group (P < 0.05). The levels of serum BDNF, NT-3 and 5-HT in the depressed group were higher than those in the non-depressed group and control group, and the levels of serum NT-3 in the non-depressed group were higher than those in the control group (P < 0.05). SAS score was positively correlated with serum NT-3 and 5-HT levels, while the SDS score was negatively correlated with serum BDNF and positively correlated with serum NT-3 and 5-HT levels. Female, rural household registration, and restless leg syndrome were independent risk variables for anxiety in patients with MHD (P < 0.05). Rural household registration, economic deterioration, fatigue, insomnia, and vascular pain were independent variables of depression risk in patients with MHD. Conclusion: Anxiety and depression in patients with MHD are closely related to the levels of serum BDNF, NT-3, and 5-HT. Female, rural household registration, more than eight dialysis times/month, insomnia, and restless leg syndrome are the risk factors for anxiety in patients with MHD. Rural household registration, economic deterioration, fatigue, insomnia, and vascular pain are the risk factors for depression in patients with MHD. The clinical implication of these findings suggests that these indexes may perhaps serve as biological indicators of anxiety and depression amongst patients undergoing MHD. Such investigation can hence contribute to early detection, monitoring, and potentially enable the depiction of novel therapeutic strategies for managing these adverse states.

Case report: A rare appearance of preretinal deposits in a patient with uveitis: multimodal imaging observation.

Background: Uveitis is a disease presenting with varied clinical symptoms and potentially devastates visual function. Here, we report a patient with uveitis exhibiting a rare appearance of preretinal deposits (PDs). Case presentation: A 49-year-old female showed vitreous opacity and perivascular white PDs involving veins and arteries. The interferon-gamma release assay was strongly positive and chest computed tomography showed signs of calcified nodules; other tests were unremarkable. The patient was diagnosed with uveitis and tubercular infection. The patient was given systemic anti-tubercular therapy and steroids, which were subsequently combined with immunosuppressants. The shrinkage of HRD was more sensitively observed with OCT than on photographs during follow-up visits. The right eye was relieved subsequently, but the left eye showed vitreous opacity and responded poorly to the treatment. Three months after the dexamethasone intravitreal implant, the perivascular deposits in the left eye disappeared and the vitreous opacity was relieved. Conclusion: PDs can appear as spotted deposits in the posterior pole and segmental deposits in the periphery in patients with uveitis, which mainly involves the vitreous cavity and is easily confused with retinal vasculitis. OCT can more sensitively observe the response than other examinations.