Objective To analyze the epidemiological characteristics and risk factors of common viruses in children with respiratory tract infection in Yangling District, and to provide scientific basis for clinical formulation of effective prevention and control strategies. Methods The study subjects were 502 children with respiratory tract infection in Yangling Demonstration Zone Hospital from February 2022 to February 2024. 10 kinds of common respiratory infection viruses such as respiratory syncytial virus, parainfluenza virus, human rhinovirus, influenza B virus, influenza A virus, human adenovirus, enterovirus, coronavirus, human metapneumovirus and human Boca virus were detected by multiple real-time fluorescent polymerase chain reaction (PCR). According to the results of viral nucleic acid detection, 502 children were divided into positive detection group and negative detection group. Univariate and logistic multivariate regression analyses were adopted to analyze the risk factors of respiratory virus infection in children. Results Among the 502 children with respiratory tract infection, 112 cases were positive for viral nucleic acid detection, with a positive rate of 22.31%. Among the 95 cases were with single virus infection with a positive rate of 18.92%, mainly respiratory syncytial virus and parainfluenza virus, and 17 cases were with mixed virus infection, with the positive rate of 3.39%, mainly respiratory syncytial virus+parainfluenza virus mixed infection. After logistic multivariate analysis, it was found that age≤1 year old, onset in autumn and winter, monthly family income≤5000 yuan, concomitant congenital heart disease, maternal atopic disease history, maternal gestational diabetes mellitus, malnutrition and anemia were independent risk factors for respiratory virus infection in children (P<0.05). Conclusion Respiratory virus infection in acute hospitalized children in Yangling District is mainly a single virus, and is affected by many factors such as age of children, onset season, family monthly income and so on. Clinically, it is necessary to actively screen the above indicators of children and take active preventive measures to reduce viral infection.

Objective:This study aimed to analyze the genetic variation of the human papillomavirus (HPV) type 39 genomes and to predict and screen the dominant T-cell and B-cell epitopes of the viral early proteins (E1, E2, E6, E7) and late proteins (L1, L2).Methods:A total of 70 full-length sequences of HPV39 variants were retrieved from the clinical samples and the National Center for Biotechnology Information (NCBI) to construct a phylogenetic tree, analyze genetic polymorphisms, and predict the physicochemical properties of the viral proteins. Next, T-cell and B-cell epitopes were predicted using IEDB and ABCpred, and potential dominant epitopes were further selected based on parameters such as the secondary structure of the epitope region, peptide flexibility, hydrophilicity, surface accessibility and antigenicity. Finally, a homology analysis of the potential dominant epitopes was performed with 12 high-risk HPV types.Results:HPV39 variants from different sources can be clustered into two lineages (A and B), each exhibiting distinct mutation patterns. The mutation rate was the highest in E7 and the lowest in E1 among the different viral genes. However, these nucleotide/amino acid mutations did not significantly impact the physicochemical properties of the viral proteins. After prediction and screening, 5 and 6 potential dominant B-cell epitopes were identified in both L1 and L2, respectively. E1, E2, E6, and E7 yielded 18, 10, 4, and 1 potential dominant HLA-I restricted T-cell epitopes, respectively. Additionally, E1, E2, and E6 yielded 7, 3, and 2 potential dominant HLA-II restricted T-cell epitopes, respectively. Homology analysis indicated that T-cell dominant epitopes in E1, E2, and E6, as well as B-cell epitopes in L2, showed high homology (93%-100%) with HPV68, HPV33, HPV45, and HPV59.Conclusions:Bioinformatics analysis and prediction revealed that HPV39 variants can be clustered into two main evolutionary branches, A and B, each exhibiting a specific mutation pattern. The viral proteins contain potential dominant T-cell and B-cell epitopes that can be further investigated, providing valuable theoretical support for the development of HPV39-related peptide-based vaccines and therapeutics.

Purpose To investigate the relationships between the genetic variations and clinicopathological fea-tures of thyroid carcinoma in a single-center cohort.Methods The correlation between genetic profiling and clinico-pathologic characteristics of thyroid carcinomas detected by next-generation sequencing was analyzed.Results 93.7％of 238 cases of thyroid cancer had Class Ⅰ or Class Ⅱ variations.Compared with TCGA cohort,the single-center of pa-tients with papillary thyroid cancer(PTC)were younger(44.4±12.4 vs 46.8±15.5,P=0.043),and the rate of lymph node metastasis was higher(57.5％vs 49.2％,P=0.046).The frequency of BRAF gene mutation was signifi-cantly higher(82.4％vs 59.7％,P＜0.001),that of RAS gene mutation(2.3％vs 12.9％,P＜0.001)and TERT promoter mutation was lower(1.8％vs 9.4％,P＜0.001).There were no differences in the incidences of RET fusion(5.4％vs 6.8％,P=0.484)and NTRK fusion(4.1％vs 2.1％,P=0.127).Gene mutations were detected in 210 of 221(95.0％)patients with PTC,including BRAF(182/221,82.4％),RET fusion(12/221,5.4％),NTRK fusion(9/221,4.1％),FGFR amplification(6/221,2.7％),CCND1 amplification(6/221,2.7％),FGFR19 am-plification(6/221,2.7％),RAS(5/221,2.3％),PIK3CA(5/221,2.3％),and TERT(4/221,1.8％).NTRK fusion was associated with younger age(P=0.049)and higher T stage(P=0.005),while TERT promoter mutation was associated with older age(P=0.003)and higher T stage(P=0.001).8.6％(19/221)of thyroid papillary car-cinoma had at least two driver gene variants and tended to occur in patients with older age(P=0.001)and higher T tage(P=0.001).Higher mutation allele fraction(MAF)of BRAF was associated with T stage(P＜0.001)and N stage(P=0.017).Conclusion Chinese patients with papillary thyroid carcinomapatients show unique genetic vari-ant characteristics,and the patients with NTRK fusion,TERT promoter mutation,multiple driver gene variations,or high MAF of BRAF show specific clinicopathologic features.

Purpose To investigate the relationships between the genetic variations and clinicopathological fea-tures of thyroid carcinoma in a single-center cohort.Methods The correlation between genetic profiling and clinico-pathologic characteristics of thyroid carcinomas detected by next-generation sequencing was analyzed.Results 93.7％of 238 cases of thyroid cancer had Class Ⅰ or Class Ⅱ variations.Compared with TCGA cohort,the single-center of pa-tients with papillary thyroid cancer(PTC)were younger(44.4±12.4 vs 46.8±15.5,P=0.043),and the rate of lymph node metastasis was higher(57.5％vs 49.2％,P=0.046).The frequency of BRAF gene mutation was signifi-cantly higher(82.4％vs 59.7％,P＜0.001),that of RAS gene mutation(2.3％vs 12.9％,P＜0.001)and TERT promoter mutation was lower(1.8％vs 9.4％,P＜0.001).There were no differences in the incidences of RET fusion(5.4％vs 6.8％,P=0.484)and NTRK fusion(4.1％vs 2.1％,P=0.127).Gene mutations were detected in 210 of 221(95.0％)patients with PTC,including BRAF(182/221,82.4％),RET fusion(12/221,5.4％),NTRK fusion(9/221,4.1％),FGFR amplification(6/221,2.7％),CCND1 amplification(6/221,2.7％),FGFR19 am-plification(6/221,2.7％),RAS(5/221,2.3％),PIK3CA(5/221,2.3％),and TERT(4/221,1.8％).NTRK fusion was associated with younger age(P=0.049)and higher T stage(P=0.005),while TERT promoter mutation was associated with older age(P=0.003)and higher T stage(P=0.001).8.6％(19/221)of thyroid papillary car-cinoma had at least two driver gene variants and tended to occur in patients with older age(P=0.001)and higher T tage(P=0.001).Higher mutation allele fraction(MAF)of BRAF was associated with T stage(P＜0.001)and N stage(P=0.017).Conclusion Chinese patients with papillary thyroid carcinomapatients show unique genetic vari-ant characteristics,and the patients with NTRK fusion,TERT promoter mutation,multiple driver gene variations,or high MAF of BRAF show specific clinicopathologic features.

Objective:This study aimed to analyze the genetic variation of the human papillomavirus (HPV) type 39 genomes and to predict and screen the dominant T-cell and B-cell epitopes of the viral early proteins (E1, E2, E6, E7) and late proteins (L1, L2).Methods:A total of 70 full-length sequences of HPV39 variants were retrieved from the clinical samples and the National Center for Biotechnology Information (NCBI) to construct a phylogenetic tree, analyze genetic polymorphisms, and predict the physicochemical properties of the viral proteins. Next, T-cell and B-cell epitopes were predicted using IEDB and ABCpred, and potential dominant epitopes were further selected based on parameters such as the secondary structure of the epitope region, peptide flexibility, hydrophilicity, surface accessibility and antigenicity. Finally, a homology analysis of the potential dominant epitopes was performed with 12 high-risk HPV types.Results:HPV39 variants from different sources can be clustered into two lineages (A and B), each exhibiting distinct mutation patterns. The mutation rate was the highest in E7 and the lowest in E1 among the different viral genes. However, these nucleotide/amino acid mutations did not significantly impact the physicochemical properties of the viral proteins. After prediction and screening, 5 and 6 potential dominant B-cell epitopes were identified in both L1 and L2, respectively. E1, E2, E6, and E7 yielded 18, 10, 4, and 1 potential dominant HLA-I restricted T-cell epitopes, respectively. Additionally, E1, E2, and E6 yielded 7, 3, and 2 potential dominant HLA-II restricted T-cell epitopes, respectively. Homology analysis indicated that T-cell dominant epitopes in E1, E2, and E6, as well as B-cell epitopes in L2, showed high homology (93%-100%) with HPV68, HPV33, HPV45, and HPV59.Conclusions:Bioinformatics analysis and prediction revealed that HPV39 variants can be clustered into two main evolutionary branches, A and B, each exhibiting a specific mutation pattern. The viral proteins contain potential dominant T-cell and B-cell epitopes that can be further investigated, providing valuable theoretical support for the development of HPV39-related peptide-based vaccines and therapeutics.

Objective:To compare the results of invasive prenatal diagnosis and preimplantation genetic testing (PGT) and explore the underlying mechanism.Methods:Clinical data of pregnant women undergoing PGT and invasive prenatal diagnosis at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2022 were collected. The results of PGT and invasive prenatal diagnosis were compared, and the outcomes of pregnancies were followed up. This study has been approved by the Medical Ethics Committee of the the Sixth Affiliated Hospital of Sun Yat-sen University (No. 2022SLYEC-491).Results:A total of 172 couples were included in this study, and 26 non-targeted variants were discovered upon prenatal diagnosis, including 10 cases (38.5%) by chromosomal karyotyping, 15 (57.7%) by chromosomal microarray analysis (CMA), and 1 (3.8%) by whole exome sequencing. The 10 karyotypic anomalies had included 6 chromosomal polymorphisms, 2 chromosomal mosaicisms, 1 paternally derived translocation, and 1 missed maternal chromosomal inversion. CMA has identified 15 copy number variations (CNVs), which included 11 microdeletions and microduplications, 3 loss of heterozygosity, and 1 low-level mosaicism of paternal uniparental disomy. One CNV was classified as pathogenic, and another one was likely pathogenic, whilst the remaining 13 were classified as variants of uncertain significance. Therefore, 8.7% of CNVs was detected by invasive prenatal diagnosis after PGT. 92.3% (24/26) of the non-targeted variants have been due to technological limitations of next-generation sequencing (NGS).Conclusion:Invasive prenatal diagnosis after PGT can detect non-targeted variants, which may further reduce the incidence of birth defects.

Purpose To study the consistency of NTRK fu-sion gene in the thyroid carcinoma detected by four technology platforms:immunohistochemistry,DNA-based NGS,FISH and qRT-PCR.Methods NTRK fusion gene was detected by FISH,immunohistochemical(IHC),DNA-based NGS and qRT-PCR in a same group of 40 clinical cases(among them,31 cases were thyroid cancer samples).Results In a group of 31 thyroid cancer cases detected by four techniques,compared with FISH,the sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and total coincidence rate(TCR)of IHC was 100%(9/9),90.9%(20/22),81.8%(9/11),100%(20/20),93.5%(29/31),respectively.The PPV of IHC was poor.The sensitivity,specificity,PPV,NPV and TCR of DNA-based NGS was 44.4%(4/9),100%(22/22),100%(4/4),81.5%(22/27),83.9%(26/31),respectively,and the sensitivity was poor.The TCR of qRT-PCR was 100%(31/31).Compared with FISH,Kappa value of IHC,DNA-based NGS and qRT-PCR was 0.853,0.532 and 1.000,respectively.Of the 40 clinical cases,the concordance between qRT-PCR and FISH was observed for 39 samples,for the qRT-PCR assay did not cover the NTRK fusion type(LM-NA:exon4-NTRK1:exon10).Compared with FISH,the coinci-dence rate of qRT-PCR was highest.Conclusion The RNA-based assay of qRT-PCR does have the advantages of high sensi-tivity and high specificity,and may be an optimal scheme for routine clinical detection of NTRK fusion variation in thyroid cancer in pathology department.

Objective:To analyze the association between NUDT15 gene polymorphism and adverse reactions induced by azathioprine (AZA) myelosuppression in patients with inflammatory bowel disease (IBD) , and to provide reference for clinical treatment of IBD. Methods:Literatures of randomized controlled trials of NUDT15 gene mutation and AZA in the treatment of IBD were searched with computer from China Knowledge Network, Wanfang database, VIP database, PubMed, Cochrane Library and Web of Science. The quality evaluation and data of studies meeting the inclusion criteria were screened and retrieved to perform meta analysis. Results:Ten literatures were enrolled including 3095 patients. Meta analysis showed that the mutation rate of NUDT15 gene in Asian IBD population was significantly higher than that of TPMT gene (21.5% vs. 2.8%, OR = 0.10, 95% CI: 0.07-0.15, P<0.001) with significant difference. NUDT15 gene mutation was significantly associated with AZA-related leukopenia ( OR = 0.40, 95% CI: 0.34-0.47, P<0.001) . IBD patients with NUDT15 mutation were more likely to develop leukopenia in the early stage of AZA application ( OR = 2.69, 95% CI: 1.67-4.33, P<0.001) . Besides, homozygous mutants of NUDT15 gene (TT type) were more likely to have grade Ⅲ-Ⅳ bone marrow suppression ( OR = 0.09, 95% CI: 0.04-0.18, P<0.001) . Conclusions:In Asian IBD population, bone marrow suppression caused by AZA is significantly associated with NUDT15 gene mutation, which is more closely associated than TPMT gene mutation and usually occurs within 8 weeks of AZA application. At the same time, homozygous mutations of NUDT15 gene (TT) increase the risk of severe myelosuppression.

Objective:To analyze the association between NUDT15 gene polymorphism and adverse reactions induced by azathioprine (AZA) myelosuppression in patients with inflammatory bowel disease (IBD) , and to provide reference for clinical treatment of IBD. Methods:Literatures of randomized controlled trials of NUDT15 gene mutation and AZA in the treatment of IBD were searched with computer from China Knowledge Network, Wanfang database, VIP database, PubMed, Cochrane Library and Web of Science. The quality evaluation and data of studies meeting the inclusion criteria were screened and retrieved to perform meta analysis. Results:Ten literatures were enrolled including 3095 patients. Meta analysis showed that the mutation rate of NUDT15 gene in Asian IBD population was significantly higher than that of TPMT gene (21.5% vs. 2.8%, OR = 0.10, 95% CI: 0.07-0.15, P<0.001) with significant difference. NUDT15 gene mutation was significantly associated with AZA-related leukopenia ( OR = 0.40, 95% CI: 0.34-0.47, P<0.001) . IBD patients with NUDT15 mutation were more likely to develop leukopenia in the early stage of AZA application ( OR = 2.69, 95% CI: 1.67-4.33, P<0.001) . Besides, homozygous mutants of NUDT15 gene (TT type) were more likely to have grade Ⅲ-Ⅳ bone marrow suppression ( OR = 0.09, 95% CI: 0.04-0.18, P<0.001) . Conclusions:In Asian IBD population, bone marrow suppression caused by AZA is significantly associated with NUDT15 gene mutation, which is more closely associated than TPMT gene mutation and usually occurs within 8 weeks of AZA application. At the same time, homozygous mutations of NUDT15 gene (TT) increase the risk of severe myelosuppression.