Objective:To analyze the clinical manifestations and explore the etiology in a family with congenital aniridia and to analyze the influence of candidate variants on the protein structure.Methods:A pedigree investigation was performed.A Han Chinese family with congenital aniridia of two generations consisting of three members from Henan Province, including one patient diagnosed with congenital aniridia, was identified and studied following their admission to Henan Eye Hospital in June 2023.A thorough medical history was obtained for the patient and their family members.Comprehensive ophthalmologic examinations were conducted, including visual acuity, intraocular pressure, anterior segment photography, color fundus photography, ultrasound biomicroscopy, and optical coherence tomography, etc.Peripheral blood samples were obtained from the family members and whole exome sequencing (WES) was performed on the patient and validated by Sanger sequencing for other members.The pathogenicity and protein structure of newly identified variant sites were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2023[06]).Written informed consent was obtained from each subject.Results:The proband is a 23-year-old male presenting with poor binocular vision, aniridia, corneal degeneration, mild lens opacity, shallow anterior chamber, elevated intraocular pressure, peripheral retinal degeneration, and macular dysplasia.The clinical phenotype of the proband's parents did not show any significant abnormality.WES identified a heterozygous frameshift and nonsense varint c. 734_735del (p.Arg245Asnfs*20) in exon 10 of the PAX6 gene, which consisited of two bases deletion at positions 734 to 735, resulting in the mutation of its arginine at position 245 to asparagine and the early appearance of a termination codon at the next 19 amino acids.The variant had not been identified in the HGMD, Clinvar, 1 000 Genomes, and gnomAD databases.Neither of the proband's parents carried the variant, consistent with the pattern of family co-segregation.Substructural analysis using the SMART tool indicated that the variant is situated within the HOX domain.Amino acid conservation analysis demonstrated that the arginine residue at position 245 in the PAX6 gene is highly conserved across multiple species, including human, house mouse, domestic dog, African clawed frog, and macaque.The variant was classified as pathogenic (PVS1+ PS2+ PM2+ PP3) based on the ACMG standards and guidelines for the interpretation of sequence variants.Protein structure analysis revealed the absence of both the homologous domain and the proline-serine-threonine-rich domain in the PAX6 protein. Conclusions:A novel pathogenic variant, c.734_735del (p.Arg245Asnfs*20), in the PAX6 gene has been identified in a family affected by congenital aniridia.This variant results in the deletion of both the PAX6 protein homology domain and the proline-serine-threonine-rich domain.

Objective:To investigate the classification of Ovarian-Adnexal Reporting and Data System(O-RADS)combined with serum carbohydrate antigen 125(CA125)and human epididymis secretion protein 4(HE4)in diagnosing the benign and malignant adnexal masses.Methods:A retrospective analysis was performed on 114 patients who were diagnosed and confirmed by pathology in Anhui Provincial Hospital from July 2022 to August 2023.All patients underwent routine ultrasound examination,serum CA125 and HE4 examination before surgery.According to the pathological result that was used as the gold standard,they were divided into benign group(87 cases)and malignant group(27 cases).The ultrasound O-RADS grading and serum indicators of the benign group and the malignant group were compared.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacies of each detection indicator in identifying benignly and malignantly adnexal tumors.Results:In the benign group with 87 patients,2 cases were class 1,and 22 cases were class 2,and 34 cases were class 3,and 29 cases were class 4 and there was no case in class 5 as O-RADS classification.In the malignant group with 27 patients,there was no case in class 1 and class 2,and 2 cases were class 3,and 13 cases were class 4,and 12 cases were class 5.The serum median of CA125 and HE4 in the malignant group were respectively 21.5(13.2,78.3)U/ml and 49.0(31.3,70.5)pmol/L,which were significantly higher than those of the benign group(Z=-2.121,-2.021,P<0.05).The accuracies of ultrasonic O-RADS classification,CA125,HE4 and combined diagnosis of them were 71%,66%,78%and 88%for all patients,respectively.According to the ROC analysis,the area under curve(AUC)of ultrasound O-RADS classification,serum CA125,HE4 and combined diagnosis of them for benignly and malignantly adnexal tumors were 0.870,0.556,0.594,and 0.898(95%CI:0.825～0.970),respectively.Conclusion:Compared with a single indicator,O-RADS classification combined with serological indicators include CA125 and HE4 has higher application value in diagnosing benign and malignant adrenal tumors,which can improve the diagnostic accuracy.

BACKGROUND: Current studies on the COVID-19 depicted a general incubation period distribution and did not examine whether the incubation period distribution varies across patients living in different geographical locations with varying environmental attributes. Profiling the incubation distributions geographically help to determine the appropriate quarantine duration for different regions. METHODS: This retrospective study mainly applied big data analytics and methodology, using the publicly accessible clinical report for patients (n = 543) confirmed as infected in Shenzhen and Hefei, China. Based on 217 patients on whom the incubation period could be identified by the epidemiological method. Statistical and econometric methods were employed to investigate how the incubation distributions varied between infected cases reported in Shenzhen and Hefei. RESULTS: The median incubation period of the COVID-19 for all the 217 infected patients was 8 days (95% CI 7 to 9), while median values were 9 days in Shenzhen and 4 days in Hefei. The incubation period probably has an inverse U-shaped association with the meteorological temperature. The warmer condition in the winter of Shenzhen, average environmental temperature between 10 °C to 15 °C, may decrease viral virulence and result in more extended incubation periods. CONCLUSION Case studies of the COVID-19 outbreak in Shenzhen and Hefei indicated that the incubation period of COVID-19 had exhibited evident geographical disparities, although the pathological causality between meteorological conditions and incubation period deserves further investigation. Methodologies based on big data released by local public health authorities are applicable for identifying incubation period and relevant epidemiological research.
Adolescent ; Adult ; Aged ; COVID-19/prevention & control* ; Child ; China/epidemiology* ; Female ; Geography ; Humans ; Infectious Disease Incubation Period ; Male ; Middle Aged ; Quarantine ; Retrospective Studies ; SARS-CoV-2 ; Young Adult