Acute Macular Neuroretinopathy after SARS-CoV-2 Infection: An Analysis of Clinical and Multimodal Imaging Characteristics.

BACKGROUND: This study aimed to analyze clinical and multimodal imaging characteristics of acute macular neuroretinopathy (AMN) post-recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Retrospective observational study. Medical records and multimodal imaging of 12 AMN eyes of eight patients (six female and two male) with recent SARS-CoV-2 infection were retrospectively analyzed. RESULTS: Four patients (50%) presented with bilateral AMN. Fundus ophthalmoscopy revealed a reddish-brown lesion around the macula, and two eyes had cotton-wool spots at the posterior pole. Three eyes showed mild hypo-autofluorescence. All FFA images (7 eyes) showed no abnormal signs. On OCT scans, all eyes showed outer nuclear layer (ONL) thinning, 8 eyes (66.7%) showed ONL hyperreflectivity, 5 eyes (41.7%) showed outer plexiform layer (OPL) hyperreflectivity, 8 eyes (66.7%) showed interdigitation zone (IZ) disruption, 11 eyes (91.6%) showed ellipsoid zone (EZ) disruption, 2 eyes (16.7%) showed cotton-wool spots and inner plexiform layer (IPL) hyperreflectivity, 1 eye (8.3%) had intraretinal cyst and 1 eye (8.3%) had inner nuclear layer (INL) thinning. Persistent scotoma, ONL hyperreflectivity and IZ/EZ disruption as well as recovery of OPL hyperreflectivity were reported after follow-up in three cases. CONCLUSIONS: AMN post-SARS-CoV-2 mostly affected young females and could present unilaterally or bilaterally. Dark lesions on IR reflectance and outer retinal hyperreflectivity on OCT are useful in diagnosing AMN. OPL/ONL hyperreflectivity on OCT could disappear after follow-up, but ONL thinning and IZ/EZ could persist.

Identifying causal associations between early sexual intercourse or number of sexual partners and major depressive disorders: A bidirectional two-sample Mendelian randomization analysis.

BACKGROUND: Early sexual intercourse and a greater number of sexual partners have been proved associated with depression. However, the causality of these associations is not clear. METHODS: To unveil the causal associations between sexual factors and major depression disorder (MDD). The bidirectional, two-sample Mendelian randomization (MR) study was conducted, which used genetic variants associated with two sexual factors (age first had sexual intercourse, n = 406,457; lifetime number of sexual partners, n = 378,882) and MDD (n = 500,199) from the largest genome-wide association studies (GWASs) conducted by the UK biobank and the Psychiatric Genomics Consortium. The two-step MR analysis was applied to assess mediation. The Genetic predictors for five risky behaviors were also obtained from the most up-to-date GWAS conducted by the UK Biobank (ever self-harmed: 117,733; ever attempted suicide: 4933; psychoactive substance abuse, alcohol use, and tobacco use: 463,010). RESULTS: MR analysis indicated a risky causal effect of age first had sexual intercourse (OR = 0.720, 95 % CI: 0.661-0.784, P = 2.45 × 10-14) and lifetime number of sexual partners (OR = 1.656, 95 % CI: 1.356-2.022, P = 7.46 × 10-7) on MDD. Mediation analysis showed the effects were mediated by tobacco use, with a proportion of 34.20 % on age first had sexual intercourse and 22.94 % on lifetime number of sexual partners separately. LIMITATIONS: The overlap of participants in different traits and unclear gender. CONCLUSIONS: Robust genetic evidence indicated that premature sexual intercourse and more sexual partners were risks for MDD. Risky behaviors, especially the tobacco use, mediated this effect.

Analysis of Systemic and Serum Risk Factors in Patients with Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.

INTRODUCTION: It remains controversial whether polypoidal choroidal vasculopathy (PCV) represents a subtype of neovascular age-related macular degeneration (nAMD) or is a distinct disease entity. This study aimed to compare and analyze systemic and serum risk factors for nAMD and PCV in an aging Chinese population. METHODS: A retrospective study was performed on 108 patients with nAMD, 131 patients with PCV, and 219 control subjects. Serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (APOA1), apolipoprotein B (APOB), complement 3 (C3), and complement 4 (C4) together with data on systemic risk factors, including hyperlipidemia, hypertension, diabetes mellitus (DM), coronary artery disease (CAD), and asthma, were collected. Chi-square tests, independent-samples t tests, and binary logistic regression analyses were performed to evaluate the associations of risk factors with nAMD and PCV. RESULTS: Patients with PCV and those with nAMD were likely to have hyperlipidemia (P < 0.001). CAD (P = 0.020) and hypertension (P = 0.006) correlated significantly with nAMD and PCV, respectively. Although no association of age and asthma with PCV or nAMD was found (P > 0.05), DM was associated with PCV development (OR = 0.535, P = 0.044). Regarding serum risk factors, HDL, LDL, TG, APOB, and C3 were significantly associated with nAMD (OR < 0.001, P < 0.001; OR = 0.028, P < 0.001; OR = 0.175, P < 0.001; OR = 0.922, P = 0.022; OR < 0.001, P < 0.001) and PCV (OR = 0.001, P = 0.001; OR = 0.097, P = 0.003; OR = 0.410, P = 0.037; OR = 0.895, P = 0.001; OR = 0.001, P < 0.001). Compared with nAMD, higher levels of HDL (P = 0.003) and LDL (P = 0.016) and lower levels of TG (P = 0.039) were found in patients with PCV, but the association of systemic risk factors between the two diseases was not significant (P > 0.05). CONCLUSION: Our findings indicate that hyperlipidemia is significantly associated with both nAMD and PCV. Serum lipid and complement levels have an effect on the pathogenesis of nAMD and PCV, and consideration of the differences between systemic and serum risk factors should be taken into account in clinical management.

Psychometric properties of the Chinese version of the Cognitive Reserve Assessment Scale in Health in patients with cancer.

BACKGROUND: Cognitive reserve is a modifiable factor that could prevent cognitive decline in patients with cancer. The Cognitive Reserve Assessment Scale in Health (CRASH) is an instrument used to assess cognitive reserve. This study aims to develop and examine the psychometric properties of the Chinese version of the CRASH for patients with cancer. METHODS: A cross-sectional survey was conducted with 167 cancer patients from four wards of two hospitals in China. Thirty-one patients were re-assessed to examine the test-retest reliability. Four translators and three reviewers developed the Chinese version of the scale. We assessed its structural validity, concurrent validity, internal consistency, test-retest reliability, measurement error, and floor/ceiling effects. RESULTS: Confirmatory factor analysis showed a good model fit with the four-factor structure of the original CRASH. The CRASH scores were statistically significantly associated with neuropsychological test scores, indicating sufficient concurrent validity. The internal consistency was acceptable, except for leisure activities, with standardized Cronbach's alphas (0.64-0.94) and standardized Omega (0.66-0.95). There was excellent test-retest reliability, with a high intraclass correlation coefficient (0.914-0.993) of total scores and scores for each domain. The measurement error was acceptable, and no floor or ceiling effects were observed. CONCLUSIONS: The Chinese version of the CRASH is a valid and reliable instrument to assess cognitive reserve in patients with cancer. Moreover, cognitive reserve measured by the CRASH was associated with low cognitive performance in cancer patients.

Protective effects of safranal on diabetic retinopathy in human microvascular endothelial cells and related pathways analyzed with transcriptome sequencing.

Aim: To determine the effect of safranal on diabetic retinopathy in vitro and its possible mechanisms. Methods: We used human retinal microvascular endothelial cells (HRMECs) to test the influence of safranal in vitro. High glucose damage was established and an safranal was tested at various concentrations for its potential to reduce cell viability using the MTT assay. We also employed apoptosis detection, cell cycle detection, a transwell test, and a tube formation assay to look into safranal's inhibitory effects on high glucose damage at various doses. Furthermore, mRNA transcriptome sequencing was performed. mRNA expression levels in a high glucose damage model, a high glucose damage model treated with safranal, and a blank control were compared to find the possible signaling pathway. Western blotting was used to confirm the expressions of several molecules and the levels of phosphorylation in each for the newly discovered pathway. Results: Cell proliferation was inhibited under a high glucose condition but could be protected by safranal at different concentrations (P<0.001). Flow cytometry results suggested safranal also protected cells from apoptosis (P=0.006). A transwell test demonstrated reduced invasiveness of safranal-treated cells in a high glucose condition (P<0.001). In a tube formation investigation, there were noticeably more new branches in the high gloucose group compared to a high glucose treated with safranal group (P<0.001). In mRNA expression patterns on transcriptome sequencing, the MAPK signaling pathway showed an expression ratio. With western blotting, the phosphorylation level of p38-AKT was elevated under a high glucose condition but could be inhibited by safranal. The expression of molecules associated with cell adhesion, including E-cadherin, N-cadherin, Snail, Twist, and fibronectin also changed significantly after safranal treatment under a high glucose condition. Conclusion: Safranal can protect diabetic retinopathy in vitro, and the p38-AKT signaling pathway was found to be involved in the pathogenesis of diabetic retinopathy and could be inhibited by safranal. This pathway may play a role by influencing cell migration and adhesion.

Asthma Promotes Choroidal Neovascularization via the Transforming Growth Factor Beta1/Smad Signalling Pathway in a Mouse Model.

INTRODUCTION: The association between age-related macular degeneration and asthma is controversial. Transforming growth factor beta (TGF-ß), which plays a critical role in asthma, has been extensively studied with regard to its function in choroidal neovascularization (CNV). In the present study, we aimed to investigate the role of TGF-ß and the possible mechanism of CNV formation complicated with asthma and to explore the effect of a TGF-ß inhibitor on CNV development in asthma mouse models. METHODS: Laser-induced CNV and ovalbumin-induced asthma mouse models were divided into 5 groups: control group, acute asthma group, chronic asthma group, inhibitor-treated acute asthma group, and inhibitor-treated chronic asthma group. The gene expression patterns of angiogenic cytokines, vascular endothelial growth factor (VEGF) receptors and inflammasomes in the control group, acute asthma group, and chronic asthma group were detected using a QuantiGene Plex 6.0 Reagent System. Fundus fluorescein angiography and histology of CNV lesions stained with haematoxylin-eosin were performed to evaluate CNV formation. Quantitative real-time PCR and western blotting were used to assess TGF-ß1, TGF-ß2, and VEGF expression and Smad2/3, AKT, p38 MAPK, and ERK1/2 signal transduction and phosphorylation in retinal and choroidal tissues from each group. RESULTS: In this study, we verified that laser treatment led to more CNV and vascular leakage in asthmatic mice than that in control mice. The changes were particularly notable in the chronic asthma group. The respective TGF-ß1, VEGF, and phosphorylated Smad2/3 (p-Smad2/3) mRNA and protein levels in retinal and choroidal tissues were significantly upregulated in both the acute and chronic asthma groups. After injection of a TGF-ß inhibitor, a distinct decline in VEGF, TGF-ß1, and p-Smad2/3 protein and mRNA levels was observed, and the mean CNV area also decreased. CONCLUSION: We provide new evidence that asthma could be a risk factor for CNV development via the TGF-ß1/Smad signalling pathway. A TGF-ß inhibitor can be applied as a useful, adjunctive therapeutic strategy for preventing CNV formation in asthmatic patients.

A comparison between the therapeutic effects of Conbercept combined with panretinal photocoagulation and panretinal photocoagulation monotherapy for high-risk proliferative diabetic retinopathy.

Objective: To compare the therapeutic effects of the administration of intravitreal Conbercept (IVC) plus panretinal photocoagulation (PRP) to that of PRP monotherapy in patients with high-risk proliferative diabetic retinopathy (PDR). Methods: In this retrospective consecutive case series, we analyzed the data on high-risk PDR patients followed up for 12 months. Patients were divided into two groups: the IVC+PRP group and the PRP monotherapy group. Patients in the IVC+PRP group were initially administered 3 IVC injections and PRP, while patients in the PRP monotherapy group received PRP only. Depending on the grouping criteria, patients in both groups were administered either IVC+PRP or PRP only if the neovascularization (NV) did not regress. From the initiation to month 12 of treatment, we recorded and compared the data on the NV regression rate, improvement in best-corrected visual acuity (BCVA), laser spots, changes in central macular thickness (CMT), complications, and the need for vitrectomy for all patients. Results: In this study, 79 eyes of 58 patients in the IVC+PRP group and 86 eyes of 60 patients in the PRP monotherapy group were included. During the follow-up of 12 months, the number of eyes with complete regression, partial regression, and no regression or increase in NV were 56 (70.88%), 23 (29.12%), and 0 (0%) in the IVC+PRP group and 13 (15.12%), 50 (58.14%), and 23 (26.74%) in the PRP group (p < 0.001). The BCVA was significantly higher and CMT was lower in the patients of the IVC+PRP group than in the PRP monotherapy group at 3, 6, and 12 months of follow-up (p < 0.05). The mean number of laser spots was lower in the patients of the IVC+PRP group than in the PRP group (1,453 ± 87 spots vs. 2,267 ± 94 spots, p < 0.05). A significantly lower percentage of patients in the IVC+PRP group underwent vitrectomy than that in the PRP group (7 (8.86%) vs. 27 (31.40%), p < 0.001). Conclusion: High-risk PDR patients treated with IVC + PRP showed a higher rate of NV regression, more effective improvement in the BCVA, and lower vitrectomy rate compared to those who were administered PRP monotherapy.

Characteristics and subtypes of depressive symptoms in Chinese female breast cancer patients of different ages: a cross-sectional study.

PURPOSE: To identify the characteristics and subtypes of depressive symptoms and explore the relationship between depressive subtypes and age among Chinese female breast cancer patients. METHOD: In this cross-sectional study, 566 breast cancer patients were recruited from three tertiary comprehensive hospital in Shandong Province, China through convenient sampling from April 2013 to June 2019. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9). Data analyses included descriptive analyses, latent class analysis. RESULTS: There were significant differences in specific depressive symptoms by age group, but no significant difference in total scores on PHQ-9. The depressive subtypes were severe (Class 4), relatively severe (Class 3; with lower psychomotor agitation/retardation and suicidal ideation), moderate (Class 2; with higher psychomotor agitation/retardation and suicidal ideation), and mild depressive symptoms (Class 1). The distribution of depression subtypes is different in various age groups. In the 45-59 age groups, severe symptoms subtype showed the highest ratios (i.e. 50.3%). CONCLUSION: This is the first study that analyses depressive symptom characteristics and identifies depressive subtypes in Chinese women with breast cancer across ages to explore symptom heterogeneity. Our findings can contribute to identifying the mechanisms behind these relationships and developing targeted interventions for patients with specific depressive subtypes.

Association analysis between the interaction of RAS family genes mutations and papillary thyroid carcinoma in the Han Chinese population.

Papillary thyroid carcinoma (PTC) is the major subtype of thyroid cancer, accounting for 75%-85% of all thyroid malignancies. This study aimed to identify the association between the interactions of single nucleotide polymorphisms (SNPs) in RAS family genes and PTC in the Han Chinese population, to provide clues to the pathogenesis and potential therapeutic targets for PTC. Hap Map and NCBI-db SNP databases were used to retrieve SNPs. Haploview 4.2 software was used to filter SNPs based on specific parameters, six SNPs of RAS gene (KRAS-rs12427141, KRAS-rs712, KRAS-rs7315339, HRAS-rs12628, NRAS-rs14804 and NRAS-rs2273267) were genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) in 673 PTC patients and 657 healthy controls, the interactive effect was evaluated by crossover analysis, logistic regression and GMDR software. We found that genetic mutation in rs712 have significant associations with PTC risk after Bonferroni correction (p<0.001). The interaction between KRAS-rs12427141 and HRAS-rs12628 increased the risk of PTC (U=-2.119, p<0.05), the interaction between KRAS-rs2273267 and HRAS-rs7315339 reduced the risk of PTC (U=2.195, p<0.05). GMDR analysis showed that the two-factor model (KRAS-rs712, NRAS-rs2273267) was the best (p=0.0107). Summarily, there are PTC-related interactions between RAS family genes polymorphisms in the Han Chinese population.

Surgical resection of primary tumor is associated with prolonged survival in low-grade pancreatic neuroendocrine tumors.

INTRODUCTION: The incidence of pancreatic neuroendocrine tumors (PNETs) is increasing over the past few decades. Surgery for low-grade and small PNETs of less than 2cm and N0M0 is still debated. The purpose of this study is to examine the association between surgical resection and survival in patients with low-grade nonfunctioning PNETs. MATERIALS AND METHODS: Patients diagnosed with PNETs between 2004 and 2015 were extracted from SEER. Kaplan-Meier methods and Cox proportional hazard models were used to estimate independent predictors in PNETs patients. RESULTS: A total of 2637 patients (2147 underwent surgical resection and 490 did not undergo surgery) with histologically confirmed low-grade PNETs in this cohort study. Overall survival (OS) and cancer-specific survival (CSS) of patients with surgery was better than those without surgery (log rank test POS<0.001, PCSS<0.001). Multivariate Cox regression analysis showed that surgical status was an independent prognostic factor associated with OS (HR 3.257, 95%CI: 2.635, 4.026) and CSS (HR 3.546, 95%CI: 2.798, 4.493). Subgroup analysis suggested the patients receiving surgery apparently had better OS and CSS regardless of tumor size (all log rank test POS<0.001, all log rank test PCSS<0.001) and SEER stage (all log rank test POS<0.001, all log rank test PCSS<0.001), compared to patients without removal of the primary tumor. CONCLUSIONS: Surgical resection of primary tumor may have a significant benefit on survival for patients with low-grade nonfunctioning PNETs. To determine the optimal management, grade, stage and tumor size should be considered comprehensively.