An Outbreak of Serogroup Y Meningococcal Meningitis in a Private Secondary Vocational School - Guangzhou City, Guangdong Province, China, 2023.

What is already known about this topic?: The inclusion of meningococcal vaccines in the National Immunization Program (NIP) over several years has significantly reduced the incidence of meningococcal meningitis in China to historic lows. Worldwide, there has been a diversification of meningococcal serogroups, leading to a shift in dominant serogroups in China from serogroup A to serogroups C and B, accompanied by a rise in reports of serogroups Y and W. What is added by this report?: An outbreak of serogroup Y Neisseria meningitidis (Nm) in a secondary vocational school involved a single confirmed severe case and 24 individuals with laboratory-confirmed Nm carriage. Epidemiological investigation revealed that the outbreak was localized to the classroom of the confirmed case. Prolonged close contact within a confined space was identified as a significant risk factor for Nm transmission. The genotype sequence identified was type 1655 (ST-1655), which is categorized under clonal complex 23 (CC-23) and bears resemblance to 8 previously confirmed cases of serogroup Y meningococcal meningitis within Guangdong Province. This suggests that serogroup Y infections continue to sporadically emerge and have become prevalent strains. What are the implications for public health practice?: This outbreak underscores the critical need to enhance surveillance of meningococcal serogroups and population carrier, and advocate for vaccination with MenY-containing vaccines.

Macular hypoplasia and high myopia in 48, xxyy syndrome: a unique case of 48, xxyy syndrome that presents with high myopia and macular dysplasia.

BACKGROUND: Among sex chromosome aneuploidies, 48, XXYY syndrome is a rare variant. This condition is marked by the existence of an additional X and Y chromosome in males, leading to a diverse range of physical, neurocognitive, behavioral, and psychological manifestations. Typical characteristics include a tall stature and infertility. Other phenotypes include congenital heart defects, skeletal anomalies, tremors, obesity, as well as the potential for type 2 diabetes and/or peripheral vascular disease. CASE PRESENTATION: A 6-year-old boy, who had been experiencing progressive vision deterioration in both eyes for the past two years, presented with a history of poor vision, delayed motor skills. The patient was diagnosed with micropenis in the pediatric outpatient clinic. Sparse hair, an unusually tall stature and craniofacial dysmorphology characterized by ocular hypertelorism, depressed nasal bridge, and epicanthic folds were observed. Comprehensive ophthalmic examination revealed high myopia and grade 3 macular hypoplasia. Diagnostic investigations including karyotype analysis and whole-exome sequencing identified an anomalous male karyotype comprising two X and two Y chromosomes, confirming a diagnosis of 48, XXYY syndrome. CONCLUSIONS: This study underscores the rare association of high myopia and grade 3 macular dysplasia with 48, XXYY syndrome. To our knowledge, this case marks the first recorded instance of macular dysplasia in a patient with 48, XXYY syndrome. This novel finding enhances our understanding of this syndrome's phenotypic variability.

Genotype-Phenotype of CRB1-Associated Early-Onset Retinal Dystrophy: Novel Insights on Retinal Architecture and Therapeutic Window for Clinical Trials.

Purpose: The purpose of this study was to investigate the genotypic and phenotypic characteristics of CRB1-associated early onset retinal dystrophy (CRB1-eoRD) and retinal architecture by swept-source optical coherence tomography (SS-OCT). Methods: Eleven probands with CRB1-eoRD were recruited. Clinical information, genetic analysis, and comprehensive ophthalmic examinations including SS-OCT and SS-OCT angiography (SS-OCTA) were conducted. Results: A total of 81.8% (9/11) of CRB1-eoRD presented as Leber congenital amaurosis (LCA). Common clinical manifestations included coin-like yellow-white retinal spots (20/22, 90.9%) and para-arteriolar retinal pigment epithelial retention (12/22, 54.5%). Nineteen different CRB1 variants were detected in our case series, including 12 missense, 3 frameshifts, 3 nonsense, and 1 splicing. Of them, 12 variants had been reported, and 7 were novel. SS-OCT showed thinner central macula (the LCA group, P < 0.0001), thicker total retina (P < 0.0001), thinner outer retina (P < 0.05), and thicker inner retina (P < 0.0001) compared with the healthy control. The inner/outer (I/O) retina thickness ratio of CRB1-eoRD was 3.0, higher than the healthy control of 1.2 and other inherited retinal diseases (IRDs) of 2.2 (P < 0.0001 and P = 0.0027, respectively). SS-OCTA revealed an increased vascular density and perfusion area of the superficial vascular complex and deep vascular complex in CRB1-eoRD. Conclusions: LCA emerges as a frequently occurring phenotype in CRB1-eoRD. The unique features of SS-OCT and SS-OCTA are illustrated, and the novel biomarker, I/O ratio, may facilitate early diagnosis. The insights gained from this study hold significant value in determining the treatment window for potential forthcoming CRB1 gene therapy.

Toxocara canis infection in multiple types of animals: ophthalmological and pathological observations.

Human ocular toxocariasis (OT), caused by pet roundworm Toxocara canis (Nematoda Ascaridoidea), is a worldwide ocular parasitic infection that poses a severe threat to eyesight, especially in school-aged children. However, the infection process and pathological mechanism of Toxocara are difficult to study in the human body. This study was designed to explore long-term ocular manifestations in different rodents infected with Toxocara canis, uncovering the specific pathological mechanism and migration pathway of larvae after infection. The three types of experimental animals we selected were C57BL/6 mice, Mongolian gerbils and Brown Norway rats. Mice were randomly divided into five groups and infected orally with 1000, 2000, 4000, 8000 and 10,000 T. canis eggs; gerbils were randomly divided into four groups and infected orally with 1000, 2000, 4000 and 10,000 T. canis eggs; rats were randomly divided into three groups and infected orally with 2000, 6000 and 10,000 T. canis eggs. Their ocular changes were closely observed and recorded for at least 2 months. We also enucleated the eyeballs of some animals to perform pathological sectioning and hematoxylin-eosin staining. After 3 dpi (days post-infection), hemorrhagic lesions, mechanical injury of the retina and larval migration could be observed in some infected animals. The ocular infection and mortality rates tended to be stable at 7 dpi. Larval tissue, structure disorder and inflammation could be observed in the pathological sections. In conclusion, the mice infected with 2000 T. canis eggs and gerbils infected with 1000, 2000 and 4000 T. canis eggs showing obvious ocular lesions and lower mortality rates could provide a basis for long-term observation.

Serological investigation on the prevalence of poliovirus in Guangdong province: A cross-sectional study.

In 2019, we conducted a cross-sectional study for polio virus seroprevalence in Guangdong province, China. We assessed the positivity rates of poliomyelitis NA and GMT in serum across various demographic groups, and the current findings were compared with pre-switch data from 2014. Using multistage random sampling method, four counties/districts were randomly selected per city, and within each, one general hospital and two township hospitals were chosen. Healthy individuals coming for medical checkups or vaccination were invited. A total of 1318 individual samples were collected and tested. In non-newborn population, age-dependent positivity rates ranged from 77.8% to 100% for PV1 NA and 70.3% to 98.9% for PV3 NA (p < .01). The lowest GMT values for both types (17.03 and 8.46) occurred in the 20 to <30 years age group, while peak GMTs for PV1 and PV3 were observed in 1 to <2 (340.14) and 0 to <1-year (168.90) age groups, respectively. GMTs for PV1 (P = .002) and PV3 (P = .007) in Eastern Guangdong were lower than those in the other three regions. Male participants showed higher GMTs than females (P = .016 and .033, respectively). In newborn population, both males and females showed higher PV1 NA positivity rates and GMTs compared to PV3 (p < .05). Post-switch PV3 NA positivity rates were higher than pre-switch rates (p = .016). GMTs of both PV1 and PV3 were significantly higher post-switch (p < .001). The positivity rates of NAs and GMTs remain high level, which play an important role in resisting poliomyelitis infection. Effect of the converted immunization program was more pronounced than that before.

Highly stable and reversible Zn anodes enabled by an electrolyte additive of sucrose.

Aqueous zinc-ion batteries (ZIBs) are one of the most promising candidates for electric energy storage devices due to their merits of low cost and high safety. However, the notorious side reactions and dendrite formation on zinc anodes impede the commercialization of ZIBs. In this work, a cheap and edible electrolyte additive sucrose is applied to address the above issues. Sucrose with hydroxyl groups can react as zincophilic sites to adsorb Zn2+. As verified by Raman and FT-IR spectroscopy, the solvation structure of Zn2+ and the hydrogen bonds can be regulated by the sucrose molecule. The weakened solvated structure of Zn2+ and lowered coupling degree between Zn2+ and SO42- can inhibit the hydrogen evolution reaction (HER) and the generation of the sulfate by-product. Furthermore, a solid electrolyte interphase (SEI)-like ion buffer layer is formed because of the preferentially adsorbed sucrose, which can increase the nucleation overpotential and equalize the ion distribution. The enriched Zn nucleation sites and inhibited 2D diffusion of Zn2+ resulting from the sucrose additive enable uniform Zn deposition. Thus, improved performances of symmetric Zn||Zn, asymmetric Zn||Cu and Zn||VO2 cells are realized. The Zn||Zn cell exhibits a highly reversible cycling performance for 1200 h and 400 h at 5 mA cm-2/1 mA h cm-2 and 10 mA cm-2/5 mA h cm-2, respectively. This work provides a readily available and edible additive to improve the performance of ZIBs.

Safety and effectiveness of intravitreal dexamethasone implant in patients with ocular toxocariasis.

AIMS: To evaluate the safety and effectiveness of intravitreal dexamethasone (DEX) implant in patients with active uveitis due to ocular toxocariasis (OT). METHODS: Seventy-eight patients with OT were recruited in this retrospective study, including 51 patients in DEX group treated with intravitreal DEX implant and 27 patients in control group without intervention. The reduction of vitreous haze scores (VHS), the best-corrected visual acuity (BCVA) changes, intraocular pressure (IOP) and cataract progression and formation were recorded at baseline (V0), 1 (V1), 3 (V3) and 6 months (V6) after treatment in DEX group, and V0 and V6 in control group. RESULTS: There was no change in VHS and BCVA in control group between V0 and V6. Better VHS (p=0.001) and BCVA (p=0.022) was achieved in DEX group; the rate of VHS=0 was 0%, 67.4%, 42.9% and 44.9% at V0, V1, V3 and V6, respectively (p＜0.001), and the mean BCVA was improved from logMAR 1.5±0.9 to 1.2±0.9 at V1, 1.4±1.0 at V3 and 1.4±1.2 at V6. A favourable BCVA at V1 was associated with older age (p=0.038) and uninvolved macula (p=0.000) in DEX group. No significant difference in IOP elevation ≥10 mm Hg, cataract progression and formation between groups. More eyes needed retinal surgery in control group (p<0.001). CONCLUSIONS: This was the first study to investigate use of intravitreal DEX implant in OT patients, which can efficiently reduce ocular inflammation and improve BCVA in macular uninvolved patients.

Achieving the High Capacity and High Stability of Li-Rich Oxide Cathode in Garnet-Based Solid-State Battery.

Solid-state batteries (SSBs) based on Li-rich Mn-based oxide (LRMO) cathodes attract much attention because of their high energy density as well as high safety. But their development was seriously hindered by the interfacial instability and inferior electrochemical performance. Herein, we design a three-dimensional foam-structured GaN-Li composite anode and successfully construct a high-performance SSB based on Co-free Li1.2 Ni0.2 Mn0.6 O2 cathode and Li6.5 La3 Zr1.5 Ta0.5 O12 (LLZTO) solid electrolyte. The interfacial resistance is considerably reduced to only 1.53â€…Ω cm2 and the assembled Li symmetric cell is stably cycled more than 10,000 h at 0.1-0.2 mA cm-2 . The full battery shows a high initial capacity of 245 mAh g-1 at 0.1 C and does not show any capacity degradation after 200 cycles at 0.2 C (≈100 %). The voltage decay is well suppressed and it is significantly decreased from 2.96 mV/cycle to only 0.66 mV/cycle. The SSB also shows a very high rate capability (≈170 mAh g-1 at 1 C) comparable to a liquid electrolyte-based battery. Moreover, the oxygen anion redox (OAR) reversibility of LRMO in SSB is much higher than that in liquid electrolyte-based cells. This study offers a distinct strategy for constructing high-performance LRMO-based SSBs and sheds light on the development and application of high-energy density SSBs.

HIGH MYOPIA IS COMMON IN PATIENTS WITH X-LINKED RETINOPATHIES: Myopic Maculopathy Analysis.

PURPOSE: High myopia can occur as a single or syndromic condition. The aim of this study was to evaluate the refractive error and myopic maculopathy in patients with X-linked retinopathies. METHODS: Whole exome sequencing, Sanger sequencing, and comprehensive ocular examinations were performed in patients with X-linked retinopathies. RESULTS: A total of 17 patients were recruited, including six with CACNA1F, seven with RPGR, three with NYX, and one with OPN1MW mutations. The diagnoses were congenital stationary night blindness (6), cone-rod dystrophy (4), retinitis pigmentosa (4), achromatopsia (1), Leber congenital amaurosis (1), and myopia (1). Myopia was present in 88.2% patients, and 64.7% patients had high myopia. Gene analysis showed that high myopia was present in 80% patients with CACNA1F, 100% patients with NYX, and 57.1% patients with RPGR mutations. In the ATN classification, 64.7% of the patients were A1T0N0 and 35.3% were A0T0N0. The refractive errors progressed over time, even in patients with congenital stationary night blindness. Two females with heterozygous de novo RPGR mutations presented with retinitis pigmentosa or cone rod dystrophy combined with high myopia. CONCLUSION: High myopia is common in patients with X-linked retinopathies, and myopic maculopathy was only mild atrophy without traction and neovascularization.

Case report: A frameshift mutation in CLCN2-related leukoencephalopathy and retinopathy.

Background: Leukoencephalopathy and visual impairment have been linked to loss-of-function mutations in the CLCN2 gene (MIM #600570). However, the ocular features caused by the CLCN2 mutations remain poorly understood and seldom reported. This study aims to present a novel mutation and characterize the ocular phenotype in a Chinese female diagnosed with CLCN2-related leukoencephalopathy (CC2L), also known as leukoencephalopathy with ataxia (LKPAT; MIM #615651). Case presentation: A 20-year-old Chinese female presented with bilateral blurred vision persisting for 2 years, which had worsened over the past 6 months. Ophthalmologic examination revealed bilateral post-capsular cataracts, macular retinal atrophy, and peripheral retinal pigmentation. Swept-source optical coherence tomography (SS-OCT) showed bilateral choroidal capillary atrophy, loss of the outer retinal layer, and a novel noteworthy sign of vacuole-like vitreoretinopathy. Cranial magnetic resonance imaging confirmed leukoencephalopathy. Genetic testing identified a novel homozygous pathogenic c.1382_1386del (p.P461Lfs*13) mutation in exon 13 of the CLCN2 gene. Conclusion: This case report expands the knowledge of CLCN2 mutations and their associated ocular manifestations in patients with CC2L. The identified ophthalmic features may serve as crucial indicators for early diagnosis in individuals with CC2L, especially in the absence of evident neurological symptoms.

Effect of small peptide chelated iron on growth performance, immunity and intestinal health in weaned pigs.

BACKGROUND: Small peptide chelated iron (SPCI), a novel iron supplementation in pig diets, owns growth-enhancing characteristics. Although a number of researches have been performed, there is no clear-cut evidence to show the exact relationship between the dose and effects of small peptide chelated minerals. Therefore, we investigated the effect of dietary supplementation of SPCI at different doses in the growth performance, immunity, and intestinal health in weaned pigs. METHODS: Thirty weaned pigs were randomly assigned into five groups and feed with basal diet or the basal diet containing 50, 75, 100, or 125 mg/kg Fe as SPCI diets. The experiment lasted for 21 d and on day 22, blood samples were collected 1 h later. The tissue and intestinal mucosa samples were collected following. RESULTS: Our results showed that the feed to gain ratio (F:G) decreased with different levels of SPCI addition (P < 0.05). The average daily gain (ADG) (P < 0.05) and digestibility of crude protein (P < 0.01) decreased with 125 mg/kg SPCI addition. With dietary different levels of SPCI addition, the serum concentrations of ferritin (quadratic, P < 0.001), transferrin (quadratic, P < 0.001), iron content in liver (quadratic, P < 0.05), gallbladder (quadratic, P < 0.01) and fecal (quadratic, P < 0.01) increased quadraticly. While the iron content in tibia (P < 0.01) increased by 100 mg/kg SPCI supplementation. Dietary 75 mg/kg SPCI addition increased the serum insulin-like growth factor I (IGF-I) (P < 0.01) and SPCI (75 ~ 100 mg/kg) addition also increased the serum content of IgA (P < 0.01). The serum concentrations of IgG (quadratic, P < 0.05) and IgM (quadratic, P < 0.01) increased quadraticly by different levels of SPCI supplementation. Moreover, different levels of SPCI supplementation decreased the serum concentration of D-lactic acid (P < 0.01). The serum glutathione peroxidase (GSH-Px) (P < 0.01) elevated but the malondialdehyde (MDA) (P < 0.05) decreased by 100 mg/kg SPCI addition. Interestingly, SPCI supplementation at 75 ~ 100 mg/kg improved the intestinal morphology and barrier function, as suggested by enhanced villus height (P < 0.01) and villus height/crypt depth (V/C) (P < 0.01) in duodenum, as well as jejunum epithelium tight-junction protein ZO-1 (P < 0.01). Moreover, SPCI supplementation at 75 ~ 100 mg/kg increased the activity of duodenal lactase (P < 0.01), jejunal sucrase (P < 0.01) and ileal maltase (P < 0.01). Importantly, the expression levels of divalent metal transporter-1(DMT1) decreased with different levels of SPCI addition (P < 0.01). In addition, dietary SPCI supplementation at 75 mg/kg elevated the expression levels of critical functional genes such as peptide transporter-1(PePT1) (P = 0.06) and zinc transporter 1 (ZnT1) (P < 0.01) in ileum. The expression levels of sodium/glucose co-transporter-1 (SGLT1) in ileum (quadratic, P < 0.05) increased quadraticly by different levels of SPCI addition and amino acid transporter-1 (CAT1) in jejunum(P < 0.05) also increased by 100 mg/kg SPCI addition. CONCLUSIONS: Dietary SPCI supplementation at 75 ~ 100 mg/kg improved growth performance by elevated immunity and intestinal health.

Effect of Anti-Allergic Therapy on Sleep Quality of Children with Allergic Conjunctivitis and Their Parents.

PURPOSE: To assess the effect of anti-allergic therapy on sleep quality of children with allergic conjunctivitis (AC) and their parents. METHODS: This prospective single-arm intervention study included 54 AC child-parent dyads. Chinese versions of the Children's Sleep Habits Questionnaire (CSHQ) and Pittsburgh Sleep Quality Index (PSQI) were used to assess the sleep quality of children and their parents, respectively. RESULTS: CSHQ and PSQI total scores were significantly decreased after treatment, with fewer children and parents reporting poor sleep quality. Part impaired sleep behaviors of children and parents can recover to the normal levels. Sleep quality improved greater in children with a severe type of AC, those with worse baseline signs, and without other allergic diseases. For both children and parents, greater improvements in sleep quality were associated with longer treatment duration and with worse baseline sleep quality. CONCLUSION: Successful management of AC improves sleep quality for both children and their parents.

The Role of Interchain Force and/or Chain Entanglement in the Melt Strength and Ductility of PLA-Based Materials.

As an eco-friendly material, PLA was a desirable alternative to polyethylene and polypropylene films due to its biodegradability. The preferable melt strength of PLA-based materials was a key factor in ensuring its processing using extrusion blow. This paper focuses on the influence of interchain force and/or chain entanglement on the melt strength and ductility of PLA-based materials in recent years. In addition, the preparation of PLA-based materials via physical blending or reactive processing was also summarized. The blending of PLA with a flexible heteropolymer, driven by the interchain force and/or chain entanglements, were characterized as a practicable method for toughening PLA-based materials. Also, the restructuring of PLA chains, by branching based on chain entanglement, was suitable for increasing chain entanglements in PLA matrix, yielding satisfactory melt strength and ductility. This review aims to elucidate the relationship between interchain forces and/or entanglement with the melt strength and ductility of PLA-based materials. An essential and systematic understanding of the tailoring melt strength and rheological properties of PLA by interchain forces and/or entanglement was apt to improve and perfect the processing technology of the extrusion blow, and consequently improve the tensile strength and toughness of PLA films.

Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification of RAD51 functions.

Patients with castration-resistant prostate cancer (CRPC) often develop drug resistance after treatment with enzalutamide. The goal of our study was to identify the key genes related to enzalutamide resistance in CRPC and to provide new gene targets for future research on improving the efficacy of enzalutamide. Differential expression genes (DEGs) associated with enzalutamide were obtained from the GSE151083 and GSE150807 datasets. We used R software, the DAVID database, protein-protein interaction networks, the Cytoscape program, and Gene Set Cancer Analysis for data analysis. The effect of RAD51 knockdown on prostate cancer (PCa) cell lines was demonstrated using Cell Counting Kit-8, clone formation, and transwell migration experiments. Six hub genes with prognostic values were screened (RAD51, BLM, DTL, RFC2, APOE, and EXO1), which were significantly associated with immune cell infiltration in PCa. High RAD51, BLM, EXO1, and RFC2 expression was associated with androgen receptor signaling pathway activation. Except for APOE, high expression of hub genes showed a significant negative correlation with the IC50 of Navitoclax and NPK76-II-72-1. RAD51 knockdown inhibited the proliferation and migration of PC3 and DU145 cell lines and promoted apoptosis. Additionally, 22Rv1 cell proliferation was more significantly inhibited with RAD51 knockdown than without RAD51 knockdown under enzalutamide treatment. Overall, six key genes associated with enzalutamide resistance were screened (RAD51, BLM, DTL, RFC2, APOE, and EXO1), which are potential therapeutic targets for enzalutamide-resistant PCa in the future.

Vaccination against Varicella Zoster Virus Infection in Less Developed Regions of Guangdong, China: A Cross-Sectional Serosurveillance Study.

Vaccination is the key to prevent varicella zoster virus (VZV) infection in children. Voluntary and self-funded strategies have led to variable vaccination rates against VZV in China. For low-income populations, in particular, the effects of VZV vaccination have been insufficiently estimated. Community-based serosurveillance was conducted in two less developed regions, Zhanjiang and Heyuan, of Guangdong, China. Anti-VZV IgG antibodies in serum were detected by ELISA. The vaccination data were derived from the Guangdong Immune Planning Information System. A total of 4221 participants were involved, of which 3377 were from three counties of Zhanjiang and the other 844 were from one county of Heyuan, Guangdong, China. The total VZV IgG seropositivity rate in vaccinated individuals was 34.30% and 42.76%, while it was 89.61% and 91.62% in non-vaccinated populations of Zhanjiang and Heyuan, respectively. The seropositivity rate increased gradually with age, reaching ~90% in the >20- to 30-year-old group. The VarV vaccination rates of children aged 1-14 years were 60.47% for one dose and 6.20% for two doses in Zhanjiang, and 52.24% for one dose and 4.48% for two doses in Heyuan. Compared with the non-vaccinated group (31.19%) and one-dose group (35.47%), the positivity rate of anti-VZV IgG antibodies was significantly higher in the two-dose group (67.86%). Before the VarV policy was reformed, the anti-VZV IgG positivity rate was 27.85% in the one-dose-vaccinated participants, which increased to 30.43% after October 2017. The high seroprevalence in participants was due to infection of VZV in Zhanjiang and Heyuan, not vaccination against VZV. Children aged 0-5 years are still vulnerable to varicella, so a two-dose vaccination program should be implemented to prevent onward transmission of VZV.

Familial Exudative Vitreoretinopathy and Systemic Abnormalities in Patients With CTNNB1 Mutations.

Purpose: Familial exudative vitreoretinopathy (FEVR) is an inherited vitreoretinopathy. This study aimed to analyze the ocular phenotypes and systemic features of patients with CTNNB1 mutations. Methods: Whole exome sequencing was performed in the probands, and Sanger sequencing was used to verify the mutations and perform segregation analysis in the available family members. A luciferase assay was used to assess the effect of the mutant ß-catenin on transcription. Comprehensive ocular examinations were performed on the probands and family members. Systemic features were evaluated and followed up. Results: A total of 763 FEVR families were enrolled. Seven different CTNNB1 mutations, including 5 novels and 2 known mutations, were detected in 8 families, accounting for 1.05% of all FEVR families. Compared to wild-type CTNNB1, the CTNNB1 mutants failed to induce luciferase reporter activity in SuperTopFlash (STF) cells. Among the 16 eyes of the 8 probands, 2 (12.5%) eyes were classified as stage 2 FEVR, 8 (50.0%) as stage 4, and 6 (37.5%) as stage 5. All the patients had varying degrees of systemic abnormalities and presented with motor, speech, and developmental delays over time. Among the eight families with CTNNB1 mutations, seven were de novo mutations, and one proband inherited the mutation from his asymptomatic mother. Conclusions: This study provides detailed descriptions of the ocular phenotypes of patients with CTNNB1 mutations that presented as severe FEVR, and accompanied with other systemic abnormalities. Five novel mutations identified in this study, expanded the mutation spectrum of CTNNB1-associated FEVR.

ULTRA-WIDEFIELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN MILD FAMILIAL EXUDATIVE VITREORETINOPATHY.

PURPOSE: To investigate ultra-widefield optical coherence tomography angiography (UWF-OCTA) to detect and evaluate mild familial exudative vitreoretinopathy and compare the detective ratio of UWF-OCTA with ultra-widefield scanning laser ophthalmoscopy and ultra-widefield fluorescein angiography. METHODS: The patients with familial exudative vitreoretinopathy were included in this study. UWF-OCTA, using a 24- × 20-mm montage, was performed for all patients. All images were independently tested for the presence of familial exudative vitreoretinopathy-associated lesions. Statistical analysis was performed with SPSS V.24.0. RESULTS: Forty-six eyes of 26 participants were included in the study. Ultra-widefield optical coherence tomography angiography was found to be greatly superior to ultra-widefield scanning laser ophthalmoscopy in detecting peripheral retinal vascular abnormality ( P < 0.001) and peripheral retinal avascular zone ( P < 0.001). The detection rates of peripheral retinal vascular abnormality, peripheral retinal avascular zone, retinal neovascularization, macular ectopia, and temporal midperipheral vitreoretinal interface abnormality were comparable with ultra-widefield fluorescein angiography images ( P > 0.05). Furthermore, vitreoretinal traction (17/46, 37%) and small foveal avascular zone (17/46, 37%) were detected effectively on UWF-OCTA. CONCLUSION: Ultra-widefield optical coherence tomography angiography is a reliable noninvasive tool to detect familial exudative vitreoretinopathy lesions, especially in mild patients or asymptomatic family members. The unique manifestation of UWF-OCTA offers an alternative to ultra-widefield fluorescein angiography for the screening and diagnosis of FEVR.

Refocus on Immunogenic Characteristics of Convalescent COVID-19 Challenged by Prototype SARS-CoV-2.

Background: Mass basic and booster immunization programs effectively contained the spread of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus, also known as COVID-19. However, the emerging Variants of Concern (VOCs) of COVID-19 evade the immune protection of the vaccine and increase the risk of reinfection. Methods: Serum antibodies of 384 COVID-19 cases recovered from SARS-CoV-2 infection were examined. Correlations between clinical symptoms and antibodies against VOCs were analyzed. Result: All 384 cases (aged 43, range 1−90) were from 15 cities of Guangdong, China. The specific IgA, IgG, and IgM antibodies could be detected within 4−6 weeks after infection. A broad cross-reaction between SARS-CoV-2 and Severe Acute Respiratory Syndrome Coronavirus, but not with Middle East Respiratory Syndrome Coronavirus was found. The titers of neutralization antibodies (NAbs) were significantly correlated with IgG (r = 0.667, p < 0.001), but showed poor neutralizing effects against VOCs. Age, fever, and hormone therapy were independent risk factors for NAbs titers reduction against VOCs. Conclusion: Humoral immunity antibodies from the original strain of COVID-19 showed weak neutralization effects against VOCs, and decreased neutralizing ability was associated with initial age, fever, and hormone therapy, which hindered the effects of the COVID-19 vaccine developed from the SARS-CoV-2 prototype virus.

Tetrahedral framework nucleic acids inhibit pathological neovascularization and vaso-obliteration in ischaemic retinopathy via PI3K/AKT/mTOR signalling pathway.

This study aimed to explore the effect and the molecular mechanism of tetrahedral framework nucleic acids (tFNAs), a novel self-assembled nanomaterial with excellent biocompatibility and superior endocytosis ability, in inhibition of pathological retinal neovascularization (RNV) and more importantly, in amelioration of vaso-obliteration (VO) in ischaemic retinopathy. tFNAs were synthesized from four single-stranded DNAs (ssDNAs). Cell proliferation, wound healing and tube formation assays were performed to explore cellular angiogenic functions in vitro. The effects of tFNAs on reducing angiogenesis and inhibiting VO were explored by oxygen-induced retinopathy (OIR) model in vivo. In vitro, tFNAs were capable to enter endothelial cells (ECs), inhibit cell proliferation, tube formation and migration under hypoxic conditions. In vivo, tFNAs successfully reduce RNV and inhibit VO in OIR model via the PI3K/AKT/mTOR/S6K pathway, while vascular endothelial growth factor fusion protein, Aflibercept, could reduce RNV but not inhibit VO. This study provides a theoretical basis for the further understanding of RNV and suggests that tFNAs might be a novel promising candidate for the treatment of blind-causing RNV.

NDP-related retinopathies: clinical phenotype of female carriers.

BACKGROUND/AIMS: Norrin cysteine knot growth factor (NDP) located on the X chromosome, was previously reported to cause Norrie disease and familial exudative vitreoretinopathy (FEVR), which are blindness-causing ocular disorders, in males. In this study, we aimed to explore the clinical characteristics of female carriers with NDP mutations. METHODS: Twelve female carriers from 11 unrelated families with pathogenic NDP mutations were recruited. Clinical data were collected from the NDP carriers. Comprehensive ocular examinations, including best corrected visual acuity, slit lamp examination, fundus photography and fundus fluorescein angiography (FFA) were evaluated. Targeted gene or whole exome sequencing was performed in the probands, and Sanger sequencing was performed to confirm NDP mutations in female carriers. RESULTS: Of the 12 females, 1 (1/12, 8.3%) presented with decreased visual acuity and 11 (11/12, 91.7%) were asymptomatic. Based on the FFA, peripheral vascular changes were noted in 66.7% (16/24) of the eyes of 75.0% (9/12) of the carriers. A total of 33.3% (8/24) had typical FEVR phenotype, 33.3% (8/24) had mild vascular abnormalities and 33.3% (8/24) was unremarkable. In addition, predominant changes such as telangiectatic endings (66.7%), anomalous circumferential vessel (37.5%), supernumerary vascular branching (33.3%), fluorescein leakage (29.2%), avascular area (8.3%), retina fold (8.3%) and peripheral straightening of retinal vessels (33.3%) were noted. CONCLUSION: Although NDP-related retinopathy is an X-linked recessive disorder, most of the female carriers of NDP exhibited clinical features of FEVR. Thus, timely examinations and lifelong monitoring should be conducted in the NDP female carriers.