[The analysis of a pedigree with hereditary coagulation factor â ¤ deficiency caused by compound heterozygous variation of F5 gene].

Objective: To analyze the gene variation of a genetic coagulation factor Ⅴ (FⅤ) deficiency pedigree and explore the molecular pathogenesis. Methods: The proband was a 32 years old female. The patient was prone to nose bleeding since childhood which was usually self-healed. On March 10, 2021, the proband went to the First Affiliated Hospital of Air Force Medical University for treatment of knee hematoma caused by a fall. None of the family members reported any history of bleeding. The prothrombin time (PT), activated partial thromboplastin time (APTT) and FⅤ activity (FⅤ: C) were detected by clotting method and the FⅤ antigen (FⅤ: Ag) was tested with enzyme-linked immunosorbent assay (ELISA). All exons and flanks of F5 gene were determined by Sanger sequencing. Clustalx-2.1-win, PolyPhen-2 and Swiss-PDBViewer software were used to analyze the conservatism of missense variation sites, whether the variations were harmful and their influences on protein structure and function. MutationTaster and NetGene2 software were used to analyze whether the splice site variation was harmful and its effect on the splice site. Results: The PT and APTT of the proband prolonged to 24.0 s and 69.8 s, respectively. The FⅤ: C and FⅤ: Ag decreased to 6% and 9%, respectively. There were compound heterozygous variations in F5 gene, which included c.911G>A heterozygous missense variation in exon 6 leading to p.Gly276Glu variation and c.5208+1G>A heterozygous missense variation in intron 15. The father and daughter had the p.Gly276Glu heterozygous variation. Her mother and son had the c.5208+1G>A heterozygous variation. Software analysis results of p.Gly276Glu heterozygous variation showed that Gly276 was conserved among homologous species, the variation was harmful, and it could affect the local structure and function of the protein. The c.5208+1G>A heterozygous variation was deleterious and resulted in the disappearance of the splice site, thereby affecting the protein function. Conclusion: The p.Gly276Glu and c.5208+1G>A compound heterozygous variants are deleterious variants associated with the patient's disease and may be the molecular pathogenesis of inherited FⅤ deficiency in this family.

Chemical and in vitro biological information to predict mouse liver toxicity using recursive random forests.

In this study, recursive random forests were used to build classification models for mouse liver toxicity. The mouse liver toxicity endpoint (67 toxic and 166 non-toxic) was a composition of four in vivo chronic systemic and carcinogenic toxicity endpoints (non-proliferative, neoplastic, proliferative and gross pathology). A multiple under-sampling approach and a shifted classification threshold of 0.288 (non-toxic < 0.288 and toxic ≥ 0.288) were used to cope with the unbalanced data. Our study showed that recursive random forests are very efficient in variable selection and for the development of predictive in silico models. Generally, over 95% redundant descriptors could be reduced from modelling for all the chemical, biological and hybrid models in this study. The predictive performance of chemical models (CCR of 0.73) is comparable with hybrid model performance (CCR of 0.74). Descriptors related to the octanol-water partition coefficient are vital for model performance. The in vitro endpoint of CYP2A2 played a key role in the development and interpretation of hybrid models. Identifying high-throughput screening assays relevant to liver toxicity would be key for improving in silico models of liver toxicity.

Epidemiology, species distribution, antifungal susceptibility, and ERG11 mutations of Candida species isolated from pregnant Chinese Han women.

The widespread use of antifungal agents has led to increasing azole resistance in Candida species. A major azole-resistance mechanism involves point mutations in the ERG11 gene, which encodes cytochrome P450 lanosterol 14a-demethylase. In this study, vaginal swabs were obtained from 657 pregnant Chinese Han women and cultured appropriately. The open reading frame of the obtained fungal species were amplified by PCR and sequenced; additionally, the ERG11 gene of the isolated Candida species was amplified and sequenced, and the antifungal susceptibility of the isolated species was determined. The vaginal swabs of 124 women produced fungal cultures; five species of Candida were isolated from the patients, among which Candida albicans was predominant. Twelve C. albicans isolates (13.8%) were resistant to fluconazole and 2 (2.2%) were resistant to itraconazole. Seventeen mutations, including 9 silent and 8 missense mutations, were identified in the ERG11 gene of 31 C. albicans isolates. Our findings suggest that infection caused by C. albicans and non-C. albicansis common in Chinese Han women of reproductive age. Moreover, the relationship between Candida infection and certain epidemiological factors emphasizes the need to educate women about the precise diagnosis and punctual treatment of vaginitis.

Intraocular paragonimiasis.

A case of intraocular paragonimiasis is reported in a 13-year-old Chinese boy. The disease manifested as repeated attacks of acute intraocular pain associated with panuveitis. A combination of inflammatory reaction and ocular findings mimicking both perforating and contusion injuries caused by the migration of the fluke within the eye characterises the infection. The living fluke was successfully extracted from the anterior chamber and identified as Paragonimus westermani.