Unveiling the seroprevalence of human papillomavirus in Guangdong, China: Implications for vaccination strategies.

Seroepidemiological characteristics of human papillomavirus (HPV) in community residents reflect natural infection and can guide the reform of vaccination programs. A population-based serological survey was conducted in Guangdong Province. Serum anti-HPV IgG antibody levels were determined by an ELISA. Neutralizing antibodies against HPV6, 11, 16, and 18 were detected via a pseudovirus-based neutralization assay (PBNA). A total of 5122 serum samples were collected from community residents, including 1989 males and 3133 females, in three cities of Guangdong Province. The rate of HPV IgG antibody positivity in females was 5.39% (95% CI: 4.6-6.2), which was greater than that in males (2.36%; 95% CI: 1.7-3.1). HPV IgG antibodies were more frequently detected in females aged 51-60 years (11.30%; 95% CI: 7.6-16.0), whereas in males, the detection increased with age and reached 4.94% (95% CI: 2.8-6.9) in the group aged ≥71 years. The seropositivity of neutralizing antibodies against HPV6 and 11 was greater than that against HPV16 and 18. The serum neutralizing antibody titers in individuals who received three doses of a vaccine were 7- to 12-fold greater than those in individuals who did not receive the vaccine. The neutralizing antibody titers slightly decreased within 40 months and ranged from 0.038 to 0.057 log ED50 per month. A moderate consistency between the HPV ELISA and PBNA results was observed (Kappa score = 0.49, r = 0.249, 0.635, 0.382, and 0.466 for HPV6, 11, 16, and 18, respectively). The HPV seropositivity rate among healthy residents of Guangdong Province was found to be low among children and adolescents and to increase with age. The serum neutralizing antibody titers were significantly greater in the vaccine group than that in the control group, and this difference persisted over time, which indicated promising protection against HPV infection.

Genomic epidemiology of CVA10 in Guangdong, China, 2013-2021.

Hand, Foot and Mouth Disease (HFMD) is a highly contagious viral illness primarily affecting children globally. A significant epidemiological transition has been noted in mainland China, characterized by a substantial increase in HFMD cases caused by non-Enterovirus A71 (EV-A71) and non-Coxsackievirus A16 (CVA16) enteroviruses (EVs). Our study conducts a retrospective examination of 36,461 EV-positive specimens collected from Guangdong, China, from 2013 to 2021. Epidemiological trends suggest that, following 2013, Coxsackievirus A6 (CVA6) and Coxsackievirus A10 (CVA10) have emerged as the primary etiological agents for HFMD. In stark contrast, the incidence of EV-A71 has sharply declined, nearing extinction after 2018. Notably, cases of CVA10 infection were considerably younger, with a median age of 1.8 years, compared to 2.3 years for those with EV-A71 infections, possibly indicating accumulated EV-A71-specific herd immunity among young children. Through extensive genomic sequencing and analysis, we identified the N136D mutation in the 2 A protein, contributing to a predominant subcluster within genogroup C of CVA10 circulating in Guangdong since 2017. Additionally, a high frequency of recombination events was observed in genogroup F of CVA10, suggesting that the prevalence of this lineage might be underrecognized. The dynamic landscape of EV genotypes, along with their potential to cause outbreaks, underscores the need to broaden surveillance efforts to include a more diverse spectrum of EV genotypes. Moreover, given the shifting dominance of EV genotypes, it may be prudent to re-evaluate and optimize existing vaccination strategies, which are currently focused primarily target EV-A71.

Spatial accessibility and inequality analysis of rabies-exposed patients to rabies post-exposure prophylaxis clinics in Guangzhou City, China.

BACKGROUND: The incidence of rabies exposure is high and increasing in China, leading to an urgent demand of rabies post-exposure prophylaxis (PEP) clinics for the injured. However, the spatial accessibility and inequality of rabies-exposed patients to rabies PEP clinics is less known in China. METHODS: Based on rabies exposure data, PEP clinic data, and resident travel origin-destination (OD) matrix data in Guangzhou City, China, we first described the incidence of rabies exposure in Guangzhou from 2020 to 2022. Then, the Gaussian two-step floating catchment area method (2SFCA) was used to analyze the spatial accessibility of rabies-exposed patients to rabies PEP clinics in Guangzhou, and the Gini coefficient and Moran's I statistics were utilized to evaluate the inequality and clustering of accessibility scores. RESULTS: From 2020 to 2022, a total of 524,160 cases of rabies exposure were reported in Guangzhou, and the incidence showed a significant increasing trend, with an average annual incidence of 932.0/100,000. Spatial accessibility analysis revealed that the overall spatial accessibility scores for three scenarios (threshold of driving duration [d0] = 30 min, 45 min, and 60 min) were 0.30 (95% CI: 0.07, 0.87), 0.28 (95% CI: 0.11, 0.53) and 0.28 (95% CI: 0.14, 0.44), respectively. Conghua, Huangpu, Zengcheng and Nansha districts had the higher accessibility scores, while Haizhu, Liwan, and Yuexiu districts exhibited lower spatial accessibility scores. The Gini coefficient and Moran's I statistics showed that there were certain inequality and clustering in the accessibility to rabies PEP clinics in Guangzhou. CONCLUSIONS: This study clarifies the heterogeneity of spatial accessibility to rabies PEP clinics, and provide valuable insights for resource allocation to achieve the WHO target of zero human dog-mediated rabies deaths by 2030.

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.

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.

Advances in non-coding RNA as a biomarker for obstructive sleep apnoea hypoventilation syndrome.

PURPOSE: Obstructive sleep apnoea hypoventilation syndrome (OSAHS) is a common sleep disorder that affects multiple body systems, which in turn is closely associated with cognitive dysfunction, diabetes mellitus, oncological cardiovascular diseases and metabolic disorders. In recent years, non-coding RNA (ncRNA) has emerged as a new opportunity for biomarker discovery. We therefore discuss the research progress and potential role of ncRNAs in obstructive sleep apnea hypoventilation syndrome. METHODS: This review systematically searched relevant academic literature from PubMed, Web of Science and other databases. During the retrieval process, a combination of keywords such as "OSAHS", "ncRNA", "lncRNA", "miRAN", "circRNA" was used for search. RESULTS: Circulating ncRNA has good area under the ROC curve, sensitivity and specificity in the diagnosis of OSAHS, and has the potential to become a diagnostic marker for OSAHS, while several circulating ncRNAs or circulating ncRNAs in combination with other tests such as the Obstructive Sleep Apnoea Screening Scale have a higher value of application as a test for OSAHS. Further analyses revealed that many circulating ncRNAs were significantly differentially expressed in the serum of OSAHS patients with different very severities, a potential marker for predicting the severity of OSAHS, and that the ncRNA content of patients' serum also had a significant effect during CPAP therapy, suggesting that it may have potential for therapeutic monitoring. Meanwhile, serum ncRNAs from patients have been shown to be effective in the diagnosis of OSAHS complications such as hypertension, Alzheimer's disease, acute myocardial infarction and atherosclerosis. The expression of up- or down-regulated ncRNAs can regulate different signalling pathways, which in turn affects various OSAHS complications such as pulmonary hypertension, diabetes mellitus, and cognitive dysfunction, and is expected to become a new direction for the treatment of these complications. CONCLUSIONS: The changes in ncRNA expression in OSAHS patients are expected to be a novel biomarker for the diagnosis and treatment of OSAHS, and can also be used as a potential biomarker for the combination of diabetes mellitus, cardiovascular disease, respiratory disease, and cognitive dysfunction in OSAHS. It is believed that the continuous progress of ncRNA-related research is expected to promote the early detection, diagnosis and treatment of OSAHS and its complications.

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.

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.

Effectiveness of Inactivated COVID-19 Vaccines Against Illness Caused by the B.1.617.2 (Delta) Variant During an Outbreak in Guangdong, China : A Cohort Study.

BACKGROUND: Real-world evidence on inactivated COVID-19 vaccines against the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2 is limited, leaving an important gap in the evidence base about inactivated COVID-19 vaccines for use by immunization programs. OBJECTIVE: To estimate inactivated vaccine effectiveness (VE) against the B.1.617.2 variant. DESIGN: Retrospective cohort study. SETTING: The study was based on the first outbreak of the B.1.617.2 variant in mainland China that was discovered and traced in Guangdong in May and June 2021. PARTICIPANTS: 10 805 adult case patients with laboratory-confirmed infection and close contacts. MEASUREMENTS: Participants were categorized as unvaccinated, partially vaccinated (1 dose), and fully vaccinated (2 doses). We estimated VE against the primary outcome of pneumonia and the secondary outcomes of infections, symptomatic infections, and severe or critical illness associated with the B.1.617.2 variant. RESULTS: Results are reported in the order of outcome severity. Of 10 805 participants, 1.3% contracted infections, 1.2% developed symptomatic infections, 1.1% had pneumonia, and 0.2% had severe or critical illness. The adjusted VEs of full vaccination were 51.8% (95% CI, 20.3% to 83.2%) against infection, 60.4% (CI, 31.8% to 88.9%) against symptomatic infection, and 78.4% (CI, 56.9% to 99.9%) against pneumonia. Also, full vaccination was 100% (CI, 98.4% to 100.0%) effective against severe or critical illness. By contrast, the adjusted VEs of partial vaccination against infection, symptomatic infection, and pneumonia were 10.7% (CI, -41.2% to 62.6%), 6.8% (CI, -47.4% to 61.0%), and 11.6% (CI, -42.6% to 65.8%), respectively. LIMITATION: Observational study with possible unmeasured confounders; insufficient data to do reliable subgroup analyses by age and vaccine brand. CONCLUSION: Full vaccination with inactivated vaccines is effective against the B.1.617.2 variant. Effort should be made to ensure full vaccination of target populations. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China and Key-Area Research and Development Program of Guangdong Province.

Ocular manifestations of Chinese patients with copy number variants in the NDP gene.

Purpose: Familial exudative vitreoretinopathy (FEVR) and Norrie disease (ND) are genetic disorders that can be caused by mutations in the NDP gene and affect retinal vasculature growth and development. This study aimed to describe the copy number variations (CNVs) in the NDP gene in Chinese FEVR families and the associated phenotypes. Methods: This study recruited 651 FEVR families. SeqCNV was used to analyze the CNVs in the families without mutations in known FEVR-associated genes. Multiplex ligation-dependent probe amplification and semiquantitative multiplex PCR were performed to verify the NDP CNVs. The probands and family members underwent complete ocular examinations. Results: NDP CNVs were identified in four patients from three unrelated families, accounting for 15% of the patients with NDP mutations and 0.46% of the entire FEVR cohort. Exon 2 deletions were detected in two families, and whole gene deletion was identified in one family. The affected individuals were born blind with total retinal detachment. Conclusions: The findings confirm that CNVs are a common NDP mutation type. The CNV-associated phenotype is congenital blindness with total retinal detachment. Antenatal genetic analyses and fetal ultrasound can facilitate early diagnosis and interventions in patients with NDP mutations.

Ocular findings and genetic test in Alström syndrome in childhood.

This study aimed to investigate the mutation spectrums and ocular features of Alström syndrome (AS) patients. Six AS patients from five unrelated families were included. Ocular and systemic examinations were performed in all subjects. Whole-exome sequencing (WES) was performed in the probands, and Sanger sequencing was performed for mutation validation and segregation analysis. Among the six patients, the first symptoms included nystagmus, poor fixation, and photophobia. Five patients had high hyperopia, four of whom (80%) were initially diagnosed with amblyopia before referral with prescribed corrective lenses and amblyopia treatment, but no improvement was obtained. Optical coherence tomography (OCT) revealed progressive damage to the photoreceptor layer, including blurred ellipsoid zone (EZ) and lack of interdigitation zone (IZ) within the macula, and thorough loss of photoreceptor layer in the peripheral retina. Electroretinograms (ERG) demonstrated severely diminished cone and rod responses. WES identified biallelic variants of ALMS1 in all the six patients, including two novels, c.3892C > T (p.Gln1298*) and c.2888_2897del (p.Ser963Thrfs*15) and five knowns, c.10819C > T (p.Arg3607Trp), c.2090C > A (p.Ser697*), c.4891C > T (p.Gln1631*), c.10825C > T (p.Arg3069*) and c.6430C > T (Arg2146*). In conclusion, this study expanded the ocular features and genotypic spectrum of AS. High hyperopia is a significant and common feature of AS. OCT and ERG are essential accessory techniques for the diagnosis of AS. If a patient had high hyperopia with a noneffective response to amblyopic treatment, the diagnosis of AS should be suspected, and detailed ocular examination, systemic evaluation, and genetic testing recommended.

Broadening the genotypic and phenotypic spectrum of MAF in three Chinese Han congenital cataracts families.

Pathogenic variants in the v-maf avian musculoaponeurotic fibrosarcoma oncogene homologue (MAF) encoding a transcription factor (from a unique subclass of basic leucine zipper transcription factors) are associated with isolated congenital cataracts (CCs) and Aymé-Gripp syndrome (AYGRPS). We collected detailed disease histories from, and performed comprehensive ophthalmic and systemic examinations in 269 patients with CCs; we then performed whole-exome sequencing. Pathogenicity assessments were evaluated using multiple predictive tools. The clinical validities of the reported gene-disease relationships for MAF genes (MAF-CCs and MAF-AYGRPS) were assessed using the ClinGen gene curation framework. We identified two novel (c.173C>A, p.Thr58Asn and c.947T>C, p. Leu316Pro) variants and one known (c.173C>T, p.Thr58Ile) MAF missense variant in three patients. We described novel phenotypes including cleft palate, macular hypoplasia, and retinal neovascularization in the peripheral avascular area and analyzed the genotype-phenotype correlations. We demonstrated associations of variants in the MAF C-terminal DNA-binding domain with CCs and associations of variants in the N-terminal transactivation domain of MAF with AYGRPS. We thus expand the genotypic and phenotypic spectrum of the MAF gene. The ClinGen gene curation framework results suggested that variants in different domains of MAF are associated with different diseases.

NONINVASIVE DIAGNOSTIC STRATEGY OF OCULAR TOXOCARIASIS BASED ON CLINICAL FEATURES.

PURPOSE: To develop a noninvasive diagnostic strategy based on the clinical manifestations of ocular toxocariasis (OT) and evaluate its sensitivity and specificity. METHODS: Patients with unilateral OT-like lesions were enrolled retrospectively and classified into OT and non-OT groups according to the immunologic diagnosis criterion of anti-OT immunoglobulin G. Nine clinical manifestations were recorded and compared between the groups. Among them, the retrolental membrane, branch-like vitreous strands, and retinal granulomas were the most common, which were further classified into three categories, including at least 1 of three signs, at least two of three signs, and all three signs positive. Diagnostic sensitivity and specificity were calculated for each strategy. RESULTS: There were 105 immunologically confirmed patients with OT and 70 patients with non-OT uveitis/vitreoretinopathy. Retinal granulomas, retrolental membrane, and branch-like vitreous strands were significantly more frequent in OT patients than in non-OT patients. At least 1 of 3 signs positive strategy showed the highest sensitivity (100.0%) but the lowest specificity (62.0%). At least 2 of 3 signs positive strategies showed 80.0% sensitivity and 94.3% specificity. All 3 signs positive strategies had the lowest sensitivity (46.7%) and the highest specificity (100.0%). The cutoff point of this revealed an area under the curve of 0.85 and a 95% confidence interval of 0.79 to 0.91. CONCLUSION: A comprehensive strategy based on at least two out of three positive signs showed excellent sensitivity and specificity and could serve as a noninvasive and fast screening strategy for the clinical diagnosis of OT.

Molecular surveillance of coxsackievirus A16 in southern China, 2008-2019.

A national surveillance system on hand, foot, and mouth disease (HFMD) was launched in 2008 in China. Since then, millions of HFMD cases have been reported each year, with enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), and coxsackievirus A6 (CV-A6) as the major causative pathogens. Long-term surveillance of viral infection rates and genetic changes is essential for understanding the disease epidemiology pattern. Here, we analyzed molecular surveillance data on CV-A16 covering a period of 12 years (2008-2019) in Guangdong, China, one of the regions reporting the largest number of HFMD cases. Full VP1 sequences of 456 strains were determined to examine the genetic diversity and changes in the distribution of CV-A16 variants. Our study revealed an irregular pattern of CV-A16 infections in Guangdong. Different from the cyclic epidemics observed in some Asia-Pacific regions, there was a continuously high CV-A16 infection rate from 2008 to 2014, and after a period of lower epidemic activity in 2015-2017, an upsurge of CV-A16 infection was observed in 2018-2019. Cocirculation of subgenotypes B1a and B1b was observed, but while subgenotype B1a was predominant from 2008 to 2012, it appears to have been replaced by B1b, which has circulated as the predominant subgenotype since 2013. Phylogenetic analysis showed that most of the circulating CV-A16 strains are endemic, with occasional transmission between neighboring regions. The re-emergence of B1a in 2016-2019 in Guangdong was likely the result of introduction(s) from Southeast Asia. These results highlight the importance of continuous molecular surveillance from different areas, which will improve our understanding of the origin of the epidemic and facilitate the development of strategies for HFMD disease control.

The spectrum of genetic mutations in patients with asymptomatic mild familial exudative vitreoretinopathy.

Familial exudative vitreoretinopathy (FEVR) is a disease exhibits a wide range of clinical signs, ranging mild peripheral retinal vascular anomalies to severe retinal detachments. Individuals with mild FEVR are frequently asymptomatic with good visual function and are often undiagnosed. However, little is known about the genetic characters of the cohort. The purpose of this study was to investigate the clinical characteristics and genetic spectrum of in patients with asymptomatic mild FEVR. Herein, sixty-two patients (124 eyes) with asymptomatic mild FEVR were studied in a case series. Comprehensive ophthalmic examinations and genetic testing were performed in all patients. Clinical examinations showed that the avascular zone was seen in all 124 eyes and was the most common abnormality observed. Increased vessel branching and straightened peripheral vessel branches were found in 122 (98.4%) eyes. Late-phase angiographic posterior and peripheral leakage (LAPPEL) was observed in 80 (64.5%) eyes and V-shape degeneration was noted in 36 (29.0%) eyes. Other manifestations including extensive anastomoses, retinal ridges, and extraretinal neovascularization, which were detected in 30 (24.2%), 10 (8.1%) and 2 (1.6%) eyes respectively. Overall, pathogenic mutations were identified in 48.4% (30/62) of individuals with asymptomatic mild FEVR. Mutations in FZD4, LRP5, TSPAN12, and KIF11 were detected in 21.0% (13/62), 12.9% (8/62), 12.9% (8/62), and 1.6% (1/62) of our patients respectively. Ten novel mutations were found. In conclusion: Pathogenic mutations in the known FEVR-associated genes were detected in nearly half (48.4%) of the asymptomatic mild FEVR cohort. Among these mutations, FZD4 was predominant, appearing in 21.0% of all individuals. Patients with asymptomatic mild FEVR should receive timely examinations, lifelong monitoring, and some of them need preventive therapy and treatment. Additionally, we discovered 10 novel variants, which may enable a deeper understanding of this disease.

Novel variants in familial exudative vitreoretinopathy patients with KIF11 mutations and the Genotype-Phenotype correlation.

Familial exudative vitreoretinopathy (FEVR) is an inherited disease characterized by abnormal development of retinal vasculature. KIF11 mutations were identified to be associated with FEVR in recent years. The purpose of this study was to investigate novel variants and describe associated ocular and extraocular phenotypes in FEVR patients with KIF11 mutations. Herein, 417 probands with clinical diagnosis of FEVR were enrolled. Genetic testing and ophthalmic examinations were performed in all subjects, and the genotype-phenotype correlation was analyzed. Overall, KIF11 mutation was identified in nine probands (9/417, 2.2%) among the patients with FEVR phenotype. There were six males and three females whose median age was six months (range: four months to six years old) at first visit. Among the detected mutations, five (55.6%) were frameshift, two (22.2%) were missense, one (11.1%) nonsense, and one (11.1%) splicing. Seven of these KIF11 mutations were detected as novel. Four (4/9, 44.4%) of the mutations were de novo. Clinical examinations showed that: four probands presented with bilateral falciform retinal fold; two with bilateral tractional retinal detachment; one was observed tractional retinal detachment in one eye and retinal fold in the other eye; one had falciform retinal fold in one eye and chorioretinal atrophy in the other eye; one exhibited rhegmatogenous retinal detachment in the left eye. Six of the probands were detected to have microcephaly. In conclusion: Most (5/9,55.6%) of the causative mutations were frameshift, and nearly half (4/9, 44.4%) of the mutations were de novo. Most (8/9, 88.9%) patients with KIF11 mutations showed typical ocular manifestations of severe FEVR. Majority (6/9, 66.7%) of the probands had a KIF11 mutation and were detected to have microcephaly. Seven of these harbored KIF11 mutations detected to be novel.

Epidemiology and HBGA-susceptibility investigation of a G9P[8] rotavirus outbreak in a school in Lechang, China.

Rotaviruses cause severe gastroenteritis in infants, in which the viruses interact with human histo-blood group antigens (HBGAs) as attachment and host susceptibility factors. While gastroenteritis outbreaks caused by rotaviruses are uncommon in adolescents, we reported here one that occurred in a middle school in China. Rectal swabs and saliva samples were collected from symptomatic and asymptomatic students, and samples were also collected from the environment. Using PCR, followed by DNA sequencing, a single G9P[8] rotavirus strain was identified as the causative agent. The attack rate of the outbreak was 13.5% for boarders, which was significantly higher than that of day students (1.8%). Person-to-person transmission was the most plausible transmission mode. The HBGA phenotypes of the individuals in the study were determined by enzyme immunoassay, using saliva samples, while recombinant VP8* protein of the causative rotavirus strain was produced for HBGA binding assays to evaluate the host susceptibility. Our data showed that secretor individuals had a significantly higher risk of infection than nonsecretors. Accordingly, the VP8* protein bound nearly all secretor saliva samples, but not those of nonsecretors, explaining the observed infection of secretor individuals only. This is the first single-outbreak-based investigation showing that P[8] rotavirus infected only secretors. Our investigation also suggests that health education of school students is an important countermeasure against an outbreak of communicable disease.

Case report: A successful combined treatment of severe lupus miliaris disseminatus faciei with oral isotretinoin and methylprednisolone.

Lupus miliaris disseminates faciei (LMDF) is a rare inflammatory dermatosis characterized by an asymptomatic papular eruption in the central face, of which the etiology and pathogenesis are not clear. There is a lack of standard treatment recommendations, especially for severe cases. Here we report a new case of successful treatment of severe LMDF by the combination therapy of oral isotretinoin and methylprednisolone.

Triclosan induces zebrafish neurotoxicity by abnormal expression of miR-219 targeting oligodendrocyte differentiation of central nervous system.

Triclosan (TCS) is ubiquitous in a wide range of personal care and consumer products, and it is acute/chronic exposure may result in several nervous system disorders. Previous studies demonstrated TCS-induced abnormal expression of miRNAs, but no investigations focused on upstream changes of miRNAs and associated molecular mechanisms. Herein, phenotype observation and behavioral analysis confirmed that TCS exposure (0, 62.5, 125, 250 µg/L) led to developmental neurotoxicity in zebrafish larvae, especially for oligodendrocyte precursor cells (OPCs). High-throughput sequencing demonstrated the critical role of miR-219 in the differentiation of OPCs. Larvae with miR-219 depletion showed the same phenotype caused by TCS. Functional tests with miR-219 knock-down and over-expression showed that miR-219 promoted differentiation of OPCs by acting on myelination inhibitors. The miR-219 also protected against TCS-induced inhibition of cell differentiation. Several epigenetic features were identified to reveal potential upstream regulatory mechanisms of miR-219. In particular, five CpG islands hyper-methylated with increasing TCS concentrations in the promoter region of miR-219. TCS inhibited OPC differentiation by influencing epigenetic effects on miR-219-related pathways, contributing to severe neurotoxicity. These findings enhance our understanding of epigenetic mechanisms affecting demyelination diseases due to TCS exposure, and also provide theoretical guidance for early intervention and gene therapy of environmentally induced diseases.

ASSESSING THE ACTIVITY OF MYOPIC CHOROIDAL NEOVASCULARIZATION: Comparison Between Optical Coherence Tomography Angiography and Dye Angiography.

PURPOSE: This study aims to suggest a novel strategy for assessing the activity of myopic choroidal neovascularization (mCNV) based on optical coherence tomography angiography (OCTA) and to compare it with traditional fundus fluorescein angiography as the gold standard. METHODS: Macular OCTA images were obtained using RTVue XR Avanti with AngioVue. Morphologic features of mCNV lesions were analyzed. Characteristics of OCTA in 41 eyes with active mCNV and 41 eyes with inactive mCNV were analyzed. Optical coherence tomography angiography parameters associated with mCNV activity and the clinical significance of their sensitivity and specificity were analyzed using fundus fluorescein angiography as the reference. RESULTS: Of the total 108 patients, 82 had OCTA images with good quality which were included in this study. Several anatomical features of the CNV lesions, including overall appearance, branching with tiny vessels, presence of anastomoses/loops, and choroidal dark halo, were considered the possible parameters associated with mCNV activity. The intra- and interobserver agreements were substantial. To evaluate the CNV activity, sensitivity of overall appearance, tiny vascular branching, and presence of anastomoses or loops were 65.9%, 82.9%, and 73.2%, respectively, whereas the specificity was 87.8%, 90.2%, and 92.7%, respectively. However, the choroidal dark halo showed low specificity (46.3%) and failed in terms of evaluating the activity of mCNV. A novel comprehensive procedure integrating branching as a major parameter and overall appearance and presence of anastomoses/loops as minor parameters was developed to evaluate mCNV activity with sensitivity of 95.1% and specificity of 85.4%. CONCLUSION: In mCNV, the acquisition rate of clear OCTA images was 75.9%. A novel comprehensive diagnostic procedure combining mCNV appearance, vascular branching, and anastomoses/loops by OCTA may be a valuable strategy to evaluate neovascular activity in mCNV.