Multicenter and multimodal imaging study reveals rare fundus lesions in patients after SARS-CoV-2 infection.

To define the characteristics of fundus manifestations in patients after SARS-CoV-2 infection with multimodal imaging techniques. This is a retrospective multicenter and multimodal imaging study including 90 patients. All patients with a visual complaint occurring immediately after SARS-CoV-2 infection were referred to six clinics between December 2022 and February 2023. Demographic information and the temporal relationship between SARS-CoV-2 infection and visual symptoms were documented. The characteristics of the fundus lesions were evaluated using multimodal imaging. Ninety patients from six hospitals were included in this study, including 24 males (26.67%) and 66 (73.33%) females. Seventy-eight patients (86.66%) (146 eyes) were diagnosed with Acute Macular Neuroretinopathy (AMN). The AMN patients were primarily young women (67.95%). Sixty-eight patients (87.18%) had AMN in both eyes. Thirty-eight eyes (24.36%) included Purtscher or Purtscher-like lesions. optical coherence tomography and infrared retinal photographs can show AMN lesions well. Eleven cases were diagnosed with simple Purtscher or Purtscher-like retinopathy (2 cases, 2.22%), Vogt‒Koyanagi‒Harada (VKH) syndrome or VKH-like uveitis (3 cases, 3.33%), multiple evanescent white-dot syndrome (MEWDS) (2 cases, 2.22%), and rhino-orbital-cerebral mucormycosis (ROCM) (5 cases, 5.56%). After SARS-CoV-2 infection, diversified fundus lesions were evident in patients with visual complaints. In this report, AMN was the dominant manifestation, followed by Purtscher or Purtscher-like retinopathy, MEWDS, VKH-like uveitis, and ROCM.

The effect of ß-Glucan induced intestinal trained immunity against Trichinella spiralis infection.

Parasitic helminth Trichinella spiralis (Ts) induce mixed Th1/Th2 response with predominant type 2 immune responses, with protective immunity mediated by interleukin (IL)-4, IL-5, and IL-13. ß-Glucan (BG) has been shown to have the ability to induce trained immunity, confers non-specific protection from secondary infections. However, whether BG-induced trained immunity played a role in protective type 2 immunity against Ts infection is unclear. In this study, BG was administered five days before Ts infection to induce trained immunity. Our findings demonstrate that BG pretreatment effectively reduced the number of T. spiralis adults and muscle larvae, whereas inhibition of trained immunity abolished the effect of BG. Additionally, we observed a significant increase in goblet cells and mucus production as evidenced by Alcian blue periodic acid-Schiff staining. Furthermore, quantitative real-time PCR analysis revealed a significant upregulation of IL-4, IL-5, and IL-13 expression in response to BG. Conversely, the inhibitor of trained immunity reversed these effects, suggesting that BG-induced trained immunity confers strong protection against Ts infection. In conclusion, these findings suggest that BG-induced trained immunity may play a role in protection against infections caused by other helminths.

Yeast ß-glucan promotes antiviral type I interferon response via dectin-1.

Pseudorabies virus (PRV), an alphaherpesvirus, is a neglected zoonotic pathogen. Dectin-1 sensing of ß-glucan (BG) induces trained immunity, which can possibly form a new strategy for the prevention of viral infection. However, alphaherpesvirus including PRV have received little to no investigation in the context of trained immunity. Here, we found that BG pretreatment improved the survival rate, weight loss outcomes, alleviated histological injury and decreased PRV copy number of tissues in PRV-infected mice. Type I interferons (IFNs) including IFN-α/ß levels in serum were significantly increased by BG. However, these effects were abrogated in the presence of Dectin-1 antagonist. Dectin-1-mediated effect of BG was also confirmed in porcine and murine macrophages. These results suggested that BG have effects on type I IFNs with antiviral property involved in Dectin-1. In piglets, oral or injected immunization with BG and PRV vaccine could significantly elevated the level of PRV-specific IgG and type I IFNs. And it also increased the antibody levels of porcine reproductive and respiratory syndrome virus vaccine and classical swine fever vaccine that were later immunized, indicating a broad-spectrum effect on improving vaccine immunity. On the premise that the cost was greatly reducing, the immunological effect of oral was better than injection administration. Our findings highlighted that BG induced type I IFNs related antiviral effect against PRV involved in Dectin-1 and potential application value as a feed additive to help control the spread of PRV and future emerging viruses.

Helminth alleviates COVID-19-related cytokine storm in an IL-9-dependent way.

Hyperactivation of pro-inflammatory type 1 cytokines (e.g., tumor necrosis factor alpha [TNF-α] and interferon gamma [IFN-γ]) mirrors the inflammation of coronavirus disease 2019. Helminths could alleviate excessive immune responses. Here, helminth Trichinella spiralis (Ts) infection was shown to protect against TNF-α- and IFN-γ-induced shock. Mechanistically, Ts-induced protection was interleukin-9 (IL-9) dependent but not IL-4Rα. Recombinant IL-9 treatment not only improved the survival of wild-type mice with TNF-α- and IFN-γ-induced shock but also that of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected K18-human angiotensin-converting enzyme 2 (hACE2) mice, emphasizing the significance of IL-9 in alleviating cytokine storm syndromes during SARS-CoV-2 infection. Interestingly, Ts excretory/secretory (TsES)-induced protection was also observed in SARS-CoV-2 infection, indicating that identifying anti-inflammatory molecules from TsES could be a novel way to mitigate adverse pathological inflammation during pathogen infection.IMPORTANCESevere coronavirus disease 2019 (COVID-19) is linked to cytokine storm triggered by type 1 pro-inflammatory immune responses. TNF-α and IFN-γ shock mirrors cytokine storm syndromes, including COVID-19. Helminths (e.g., Trichinella spiralis, Ts) can potently activate anti-inflammatory type 2 immune response. Here, we found that helminth Ts-induced protection against TNF-α and IFN-γ shock was IL-9 dependent. Treatment with recombinant IL-9 could protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in K18-hACE2 mice. Helminth Ts excretory/secretory (TsES) products also ameliorated SARS-CoV-2 infection-related cytokine storm. In conclusion, our study emphasizes the significance of IL-9 in protecting from cytokine storm syndromes associated with SARS-CoV-2 infection. Anti-inflammatory molecules from TsES could be a new source to mitigate adverse pathological inflammation associated with infections, including COVID-19.

Trichinella spiralis alleviates LPS-induced acute lung injury by modulating the protective Th2 immune response.

Sepsis is a disorder of immune regulation caused by pathogenic microorganisms. A large number of inflammatory factors and inflammatory mediators are released, resulting in systemic inflammatory response disorder and acute lung injury (ALI). Helminths infection activate Th2 cytokines and immunomodulatory pathways, which have the function of anti-infection effector molecules. The early infection of Trichinella spiralis (T. spiralis) was mainly intestinal phase. In this study, we explored the effect of intestinal phase infection of T. spiralis on LPS-induced ALI. Compared with control mice, the serum and lung tissues of T. spiralis infected mice had a significant decrease of Th1 inflammatory cytokines, a significant increase of Th2 anti-inflammatory cytokines, and a significant decrease of inflammatory cell infiltration in lung tissue. These results suggest that T. spiralis during the intestinal phase can act on distal organs (lung) and reduce LPS-induced lung inflammation, providing evidence for a potential new pathway for immune-mediated disease in helminths and a possible role for intestinal worms in the gut-lung axis.

Genetic variations of IL10 and IL6R genes in acute anterior uveitis in Han Chinese.

BACKGROUND: Several autoimmune disorders have been linked to polymorphisms in IL10 and IL6R genes. This research aimed to study whether single nucleotide polymorphisms (SNPs) in the genes of IL10 and IL6R were associated with acute anterior uveitis (AAU) in Han Chinese. METHODS: Genotyping was carried out by the iPLEX Gold Genotyping Assay. Our study comprised 420 patients with AAU and 918 healthy subjects from Han Chinese. Using the chi-square (χ2) test, alleles and genotypes were analyzed between AAU subjects and healthy controls. RESULTS: All ten SNPs were successfully genotyped and four SNPs (IL10/rs1800871, IL10/rs3021094, IL10/rs2222202, IL6R/rs4845618) exhibited weak associations with AAU, as indicated by their Puncorr values. However, upon applying the Bonferroni correction, there was no significant association between AAU and the control subjects. Additionally, the haplotype analysis of the ten SNPs revealed no association with AAU. CONCLUSION: Our findings suggested that polymorphisms of the tested ten SNPs on the IL10 and IL6R genes did not show any association with the risk of developing AAU among the Han Chinese population.

Akkermansia muciniphila: a deworming partner independent of type 2 immunity.

The gut microbiota has coevolved with the host for hundreds of millions of years, playing a beneficial role in host health. Human parasitic helminths are widespread and pose a pervasive global public health issue. Although Type 2 immunity provides partial resistance to helminth infections, the composition of the gut microbiota can change correspondingly. Therefore, it raises the question of what role the gut microbiota plays during helminth infection. Akkermansia muciniphila has emerged as a notable representative of beneficial microorganisms in the gut microbiota. Recent studies indicate that A. muciniphila is not merely associated with helminth infection but is also causally linked to infection. Here, we provide an overview of the crosstalk between A. muciniphila and enteric helminth infection. Our goal is to enhance our understanding of the interplay among A. muciniphila, helminths, and their hosts while also exploring the potential underlying mechanisms.

Regulation mechanisms of disulfidptosis-related genes in ankylosing spondylitis and inflammatory bowel disease.

Introduction: Disulfidptosis is a recently identified form of cell death that contributes to maintaining the internal environment balance of an organism. However, the molecular basis of disulfidptosis in ulcerative colitis (UC), ankylosing spondylitis (AS), and Crohn's disease (CD) has not been thoroughly explored. Methods: Firstly, the differentially expressed genes (DEGs) and disulfidptosis-associated genes (DAGs) were obtained through differential analysis between diseases (AS, CD, and UC) and control groups. After the disulfidptosis score was acquired using the single-sample gene set enrichment analysis (ssGSEA) algorithm, the DE-DAGs were screened by overlapping DAGs and DEGs of the three diseases. Next, the feature genes were selected through a combination of machine learning algorithms, receiver operating characteristic (ROC) curves, and expression analysis. Based on these feature genes, nomograms were created for AS, CD and UC. The co-feature genes were then identified by taking the intersections of the genes featured in all three diseases. Meanwhile, single-gene set enrichment analysis (GSEA) and the TF-mRNA-miRNA network were utilized to investigate the molecular mechanisms of the co-feature genes. To validate the expression differences of the co-feature genes between healthy controls and patients (AS and IBD), RT-PCR was performed. Lastly, mendelian randomization (MR) analysis was utilized to explore the causality between genetic variants of S100A12 with AS, UC and CD. Results: In this study, 11 DE-DAGs were obtained. Functional enrichment analysis revealed their involvement in cytokine production and fatty acid biosynthesis. Latterly, AS/CD/UC -feature genes were derived, and they all had decent diagnostic performance. Through evaluation, the performance of the nomogram was decent for three diseases. Then, 2 co-feature genes (S100A12 and LILRA5) were obtained. The GSEA enrichment results indicated that the co-feature genes were mainly enriched in the cytokine-cytokine receptor interaction and drug metabolism cytochrome P450. As shown by functional experiments, there was a correlation between the mRNA expression of S100A12 with AS, UC and CD. Additionally, a causal connection between S100A12 and IBD was detected through MR analysis. Discussion: In this study, 2 co-feature genes (S100A12 and LILRA5) were screened, and their functions were investigated in AS, CD and UC, providing a basis for further research into diagnosis and treatment.

Correlation of TBX21 gene polymorphisms with ankylosing spondylitis in a Chinese population.

Genome-wide association studies analysis has revealed associations between ankylosing spondylitis (AS) and loci on the TBX21 gene across various populations. This study aimed to investigate if there is a connection between a higher risk of AS in a Chinese population and two polymorphism loci on the TBX21 gene. To achieve this, we performed a case-control investigation involving 363 patients with AS and 907 healthy individuals. Genotyping was carried out using the iPLEX Gold genotyping assay. The analysis of genotypes and haplotypes was performed using SPSS 23.0 and SHEsis software. The results revealed no statistically significant correlation between the two specified single-nucleotide polymorphisms of TBX21 (rs11657479 C/T and rs4794067 C/T) and susceptibility to AS. However, upon conducting stratification analysis, our findings demonstrated a significant association between rs11657479 and susceptibility to human leucocyte antigen (HLA)-B27+ AS in allelic (C vs. T: odds ratio [OR] = 1.52, 95%CI = 1.09-2.11, corrected p [pc] = .028), heterozygous (CT vs. TT: OR = 1.63, 95%CI = 1.13-2.34, pc = .016) and dominant (CT + CC vs. TT: OR = 1.60, 95%CI = 1.12-2.28, pc = .018) models. Furthermore, the haplotype rs4794067/C-rs11657479/C of TBX21 was found to increase the risk of HLA-B27+ AS cases. In conclusion, our findings indicate a correlation between TBX21 gene polymorphism and HLA-B27+ AS patients within the Chinese population.

Associations of IL6R and IL10 Gene Polymorphisms with Susceptibility to Ankylosing Spondylitis with or without Acute Anterior Uveitis.

BACKGROUND: This research aims to explore the associations between ten candidate single nucleotide polymorphisms (SNPs) on Interleukin-6 receptor (IL6R) and Interleukin-10 (IL10) genes and ankylosing spondylitis (AS) patients with or without acute anterior uveitis (AAU). METHODS: This study involved a case-control approach that examined 354 cases with AS and AAU, 377 AS cases without AAU, and 918 healthy controls. Genotyping of ten SNPs of IL10 and IL6R genes was performed using iPLEX Gold genotyping method. The allele and genotype frequencies of cases and healthy individuals were contrasted using the chi-square test. The IL10 mRNA level in various IL10 genotypes was tested using real-time PCR. RESULTS: Two loci associated with AS with AAU were identified: IL10//rs3790622 (OR = 0.664; 95%CI = 0.503-0.878; Pc = 0.038); IL10//rs3021094 (OR = 1.365; 95%CI = 1.110-1.679; Pc = 0.032). The other eight loci located on IL10 and IL6R did not show significant associations with the diseases. Additionally, as shown by functional experiments, there was no correlation between the mRNA expression of IL10 and various genotypes. CONCLUSION: Our study suggests that the IL10 gene contributes to the susceptibility of the Chinese population to AS with AAU.

Characteristics and scoring method of computed tomography in open-globe injuries.

BACKGROUND: Open-globe injuries (OGIs) remain the important cause of visual impairment and loss in all ages. Computed Tomography (CT) is a useful and common tool in the evaluation of the injuries of the eyeball. Prognostic value of CT scan in OGIs has been evaluated in many studies. However, there is no published consistent systematic scoring method for CT scan in OGIs. The purpose of this study was to evaluate the CT characteristics of OGIs and build a scoring method according to the CT scans which may aid the clinicians in management of OGIs. METHODS: Retrospective chart review of inpatients with clinical diagnosis of OGIs between 2017 and 2021 at Department of Ophthalmology, Henan Eye Institute, Henan Eye Hospital, Henan provincial People's Hospital (Zhengzhou, China). RESULTS: There were 1120 eyes from 1117 patients included in our study. The mean age was 35.7 ± 21.9 years with the range from 1 to 91 years. Significant male predominance was noted (889, 79.6%). CT scans of the OGIs were evaluated. Abnormality of anterior segment, posterior segment, and globe contour and volume were graded respectively. The most serious abnormality of anterior segment, posterior segment, and globe contour and volume were grade 3, 4 and 3 respectively and score 3, 4 and 3 respectively. Score of the CT scans of an open-injured globe ranged from 0 to 10. The correlation coefficient between the score and wound length was 0.798. The correlation coefficient between the score and final visual acuity was 0.799. In 78 eyes with 0 score, 70 eyes (89.7%) gained final visual acuity of 0.3 or better. In 31 eyes with 10 score, 20 eyes (64.5%) underwent evisceration of the eye globe and 10 eyes got visual acuity of no light perception and 1 eye lost to follow-up. CONCLUSIONS: CT scans is a useful tool in evaluating the severity of an open-injured globe. Scoring of the CT scans of an open-injured globe is a meaningful attempt and it may provide useful prognostic information regarding the outcome of an open-injured globe.