Case report: A novel PTCH1 frameshift mutation leading to nevoid basal cell carcinoma syndrome.

A patient presenting with several basal cell carcinomas, pigmented nevi, and developmental defects was diagnosed with nevoid basal cell carcinoma syndrome. Gene panel sequencing and Sanger sequencing were used to identify a novel heterozygous frameshift mutation, c.1312dupA:p.Ser438Lysfs, in exon 9 of PTCH1. I-Tasser and PyMol analyses indicated that the mutated protein patched homolog 1 (PTCH1) lacked 12 transmembrane domains and the intracellular and extracellular rings of ECD2 compared with the wild-type protein, resulting in a remarkably different structure from that of the wild-type protein. This case extends our knowledge of the mutation spectrum of NBCCS.

Two-stage association study of mitochondrial DNA variants in allergic rhinitis.

BACKGROUND: Correlations between mitochondrial DNA (mtDNA) and allergic rhinitis (AR) have not been reported before. This study aimed to better understand the mitochondrial genome profile with AR and to investigate the associations between AR in China and the mitochondrial genome at a single variant and gene level. METHODS: Mitochondrial sequencing was conducted on a total of 134 unrelated individual subjects (68 patients with AR, 66 healthy controls) at discovery stage. Heteroplasmy was analyzed using the Mann-Whitney U test. Sequence kernel association tests (SKAT) were conducted to study the association between mitochondrial genes and AR. Single-variant analysis was performed using logistic regression analysis and further validated in 120 subjects (69 patients with AR, 51 healthy controls). Candidate genes were further explored based on differences in mRNA and protein abundance in nasal mucosal tissue. RESULTS: In the discovery stage, 886 variants, including 836 SNV and 50 indels, were identified with mitochondrial sequencing. No statistically significant differences were identified for the mitochondrial heteroplasmy or SKAT analysis between these two groups after applying a Boferroni correction. One nonsynonymous variants, rs3135028 (MT8584.G/A) in ATP6, was related to a reduced risk of AR in both the discovery and validation cohorts. Furthermore, mRNA levels of MT-ATP6 in nasal mucosal tissue were significantly lower in AR individuals than in controls (P < 0.05). CONCLUSIONS: In a two-stage analysis of associations between AR and mtDNA variations, mitochondrial gene maps of Chinese patients with AR indicated that the ATP6 gene was probably associated with AR at the single-variant level.

Identification and functional analysis of novel biomarkers in adenoid cystic carcinoma.

To explore the key genes associated with the development and progression of adenoid cystic carcinoma (ACC), with the aim of exploring novel biomarkers that can better diagnose ACC, and thus better improve patient prognosis. The GSE59701 and GSE88804 datasets (containing transcriptomic data for a total of 19 normal samples and 20 tumor samples) were downloaded from the Gene Expression Omnibus (GEO) database, combined into one dataset and used to remove batch effects using the SVA algorithm. A total of 711 differentially expressed genes (DEGs) were screened by using the limma package. The metscape database (www. metascape.org) was used for gene ontology (GO) analysis and gene-specific Kyoto Genome Encyclopedia (KEGG) pathway analysis, which showed that the main enriched pathways of DEGs were kinase activity, fertility properties, extracellular matrix structural components, tryptophan metabolism, cancer pathway, PI3K-Akt signaling pathway. The STRING database was used to construct protein-protein interaction (PPI) networks for DEGs, and Cytoscape software was used to visualize the result. Lasso regression and SVM algorithm screened 3 key genes: GABBR1, ITGA9 and MLKL. The results of GSEA on key genes showed that they are mainly enriched in pathways such as cell cycle, and taste transduction mechanisms. CIBERSORT algorithm was used to analyze immune cell infiltration, the "corrplot" package was used to analyze the interaction relationships between immune cells. Spearman correlation analysis demonstrated that GABBR1, ITGA9 and MLKL were all strongly correlated with differentially expressed immune cells. Moreover, correlation analysis of key and differentially regulated genes showed that GABBR1 and MLKL were significantly correlated with MYB and TP53, respectively. In conclusion, GABBR1, ITGA9 and MLKL affect the progression of ACC, where GABBR1 and MLKL may regulate ACC through MYB and TP53, and the relationship between ITGA9 and ECM and PI3K-Akt may have some influence on the development of ACC.

Nomogram for predicting the prognostic role in idiopathic sudden sensorineural hearing loss.

PURPOSE: A nomogram model was constructed to assist in early prediction of idiopathic sudden sensorineural hearing loss (ISSHL) prognosis. Additionally, this study contributed to evaluating and analyzing the usefulness of the nomogram model in ISSHL clinical intervention. METHODS: A retrospective analysis was performed concerning 355 ISSHL patients who were hospitalized between June 2021 and August 2022. Single-factor analysis was used to filter variables, which were subsequently used for multivariate analysis to construct a nomogram. The discriminative capability and clinical usefulness of the predictive model were estimated by calculating the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: Hearing loss type, duration from onset to treatment, vertigo, periauricular paresthesia, and batroxobin use were included in the nomogram for ISSHL. The predictive model showed fair discrimination values (AUC =0.764; 95%CI: 0.715-0.813) and was well-calibrated, the C-index was 0.746 (95%CI: 0.715-0.793) in the internal validation. DCA indicated that the model was also clinically beneficial when the threshold range was between 0.246 and 0.840. CONCLUSIONS: The nomogram prediction model may have potential clinical practicability in effectively assisting clinicians in predicting ISSHL prognosis and optimizing treatment protocols.

A model to predict a risk of allergic rhinitis based on mitochondrial DNA copy number.

PURPOSE: To determine whether mitochondrial DNA copy number (mtDNA-CN) is associated with allergic rhinitis (AR), and further establish a nomogram model for the early diagnosis of AR. METHODS: We carried out a case-control study involving a total of 134 subjects, including 66 healthy controls and 68 AR patients. The mtDNA-CN in peripheral blood of all subjects was detected by real-time fluorescence quantitative polymerase chain reaction, and general information of patients was recorded. And, least absolute shrinkage selection operator (LASSO) regression was used to screen clinically significant variables, which were substituted into a logistic regression analysis to determine independent risk factors. Next, a nomogram model was developed for the risk prediction of AR. Then, internal validation was performed with the bootstrap resampling. Ultimately, the clinical benefit and validity of the nomogram were assessed by receiver operating characteristic (ROC) curve, bias-corrected curve, and decision curve analysis (DCA). RESULTS: MtDNA-CN and total IgE were determined as independent risk factors of AR. The final model achieved an area under the ROC curve (AUC) of 0.869, and the DCA curve demonstrated that the nomogram was clinically beneficial for practical application. CONCLUSION: An increase of the mtDNA-CN was linked to the occurrence risk of AR. The nomogram prediction model based on mtDNA-CN showed the potential clinical utility in improving risk prediction and providing new insights for exploring the pathogenesis of AR.

Design, synthesis and antibacterial activities of a series of new 2-oxaisocephems.

A series of 2-oxaisocephems with a thio-substituted methyl group at the 3-position and a [2-(5-amino-1,2,4-thiadizol-3-yl)-2-(Z)-alkoxyimino]acetamido moiety at 7-position were synthesized and tested for their antibacterial activities. The analogs 17c and 17f have well-balanced potency and significantly enhanced activity as compared with the reference compound ceftazidime.

1-Methyl-3-(3-oxocyclo-hex-1-en-yl)azepan-2-one.

The title compound, C(13)H(19)NO(2), is a inter-mediate in the synthesis of the opioid analgesic meptazinol. In the crystal structure, a weak inter-molecular C-H⋯O inter-action occurs.