Objective:To identify early predictors of factors influencing the efficacy of infliximab (IFX) treatment in patients with Crohn's disease (CD) .Methods:This study is a nested case-control study, including CD patients treated with IFX at the Second Affiliated Hospital of Soochow University from November 2015 to April 2021 and at the First Affiliated Hospital of Nanjing Medical University from November 2015 to December 2022. All the patients were followed up until June 2023 and categorized into IFX non-response and treatment-effective groups based on changes in clinical symptoms and endoscopic image during the follow-up. Laboratory data of inflammatory markers, post-induction trough IFX concentration and antibody levels in both groups were retrospectively collected and compared. Logistic regression models were employed to identify potential factors associated with the risk of IFX non-responsiveness. Machine learning using random forest analysis was utilized to quantitatively assess the predictive features for IFX treatment efficacy and ROC curves was used to evaluate the model's accuracy.Results:This study included 147 CD patients undergoing IFX treatment, with 58 from the Second Affiliated Hospital of Soochow University and 89 from the First Affiliated Hospital of Nanjing Medical University. Among them, 38 were classified as the IFX non-response group, and 109 as the effective group. Patients in the IFX non-response group had lower trough concentration ( P < 0.001), higher antibody levels ( P < 0.001), and a less pronounced reduction in ESR during the induction therapy ( P < 0.001). Univariate and multi-variate Logistic regression models demonstrated that IFX trough concentration and the ratio of ESR before and after induction therapy was associated with the risk of non-responsiveness. After the induction period, for each unit increase in IFX trough concentration (1 μg/ml), the risk of IFX non-response decreased by 23% ( RR = 0.77, 95% CI = 0.68-0.89), while each doubling of the ESR ratio after induction was associated with a 1.43-fold increase in the risk of non-response ( RR = 2.43, 95% CI = 1.48-4.00). Random forest machine learning analysis revealed that IFX trough concentration below 1.5 μg/ml could predict IFX non-response, with area under the ROC curve was 0.722. Conclusion:Lower post-induction IFX trough concentrations is predictive of IFX non-response, while a lack of significant decrease in ESR during the induction phase is also significantly associated with IFX non-response.

Objective:To identify early predictors of factors influencing the efficacy of infliximab (IFX) treatment in patients with Crohn's disease (CD) .Methods:This study is a nested case-control study, including CD patients treated with IFX at the Second Affiliated Hospital of Soochow University from November 2015 to April 2021 and at the First Affiliated Hospital of Nanjing Medical University from November 2015 to December 2022. All the patients were followed up until June 2023 and categorized into IFX non-response and treatment-effective groups based on changes in clinical symptoms and endoscopic image during the follow-up. Laboratory data of inflammatory markers, post-induction trough IFX concentration and antibody levels in both groups were retrospectively collected and compared. Logistic regression models were employed to identify potential factors associated with the risk of IFX non-responsiveness. Machine learning using random forest analysis was utilized to quantitatively assess the predictive features for IFX treatment efficacy and ROC curves was used to evaluate the model's accuracy.Results:This study included 147 CD patients undergoing IFX treatment, with 58 from the Second Affiliated Hospital of Soochow University and 89 from the First Affiliated Hospital of Nanjing Medical University. Among them, 38 were classified as the IFX non-response group, and 109 as the effective group. Patients in the IFX non-response group had lower trough concentration ( P < 0.001), higher antibody levels ( P < 0.001), and a less pronounced reduction in ESR during the induction therapy ( P < 0.001). Univariate and multi-variate Logistic regression models demonstrated that IFX trough concentration and the ratio of ESR before and after induction therapy was associated with the risk of non-responsiveness. After the induction period, for each unit increase in IFX trough concentration (1 μg/ml), the risk of IFX non-response decreased by 23% ( RR = 0.77, 95% CI = 0.68-0.89), while each doubling of the ESR ratio after induction was associated with a 1.43-fold increase in the risk of non-response ( RR = 2.43, 95% CI = 1.48-4.00). Random forest machine learning analysis revealed that IFX trough concentration below 1.5 μg/ml could predict IFX non-response, with area under the ROC curve was 0.722. Conclusion:Lower post-induction IFX trough concentrations is predictive of IFX non-response, while a lack of significant decrease in ESR during the induction phase is also significantly associated with IFX non-response.

To investigate the drug-resistance mutations and treatment of hospitalized children with Mycoplasma pneumoniae pneumonia (MPP) in Hunan Province. Children with pneumonia, who were hospitalized in the pediatric ward of the Second Xiangya Hospital of Central South University from January 1, 2023, to December 31, 2023, were enrolled in this study, and their clinical data was also collected. The targeted next-generation sequencing (tNGS) was used to detect Mycoplasma pneumoniae (MP) infection and drug-resistance mutations, and the drug-resistance and treatment in children with MPP were also analyzed. A total of 125 children with pneumonia were involved in this study, including 70 children in the MPP group and 55 children in the bacterial pneumonia group. The results showed that there were 41 boys and 29 girls with an average age of (6.50±3.45) years, with the most common group being the school-age group (age≥6 years). The clinical symptoms were characterized by fever and cough. Laboratory examination showed that the white blood cell and neutrophil counts in the MPP group were lower than those in the bacterial pneumonia group, while the lymphocyte ratio and hemoglobin levels in the MPP group were higher than those in the bacterial pneumonia group, with statistically significant differences (all P<0.05). Twelve children (17.14%) in the MPP group had severe pneumonia, and all children with severe pneumonia had 23Sr RNA A2063G and/or A2064G mutations. The tNGS detected 60 cases of MPP resistance gene mutations, including 59 cases (98.33%) of A2063G mutation in 23Sr RNA and one case (1.67%) of A2064G mutation in 23Sr RNA. There was a significant difference in the positive rate of drug-resistance mutations among patients of different age groups (χ 2=7.991, P=0.021). A total of 63 children (90.00%) with MPP were treated according to the results of drug-resistance mutations, and seven children (70.00%) with MPP without drug-resistance mutations were treated according to the tNGS results. In children with the drug resistance of MPP, 46 cases (95.83%) of non-severe pneumonia and 10 cases (83.33%) of severe pneumonia were treated according to the tNGS results. All patients had a good prognosis, with no deaths reported and a median hospital stay M ( Q1, Q3) of 9 (7, 11) days. In conclusion, MPP is more common in children aged≥6 years old in Hunan Province, and the detection of drug-resistant mutations includes A2063G and A2064G, with A2063G being the main one. The positive rate of drug-resistant mutations is related to age.

To investigate the drug-resistance mutations and treatment of hospitalized children with Mycoplasma pneumoniae pneumonia (MPP) in Hunan Province. Children with pneumonia, who were hospitalized in the pediatric ward of the Second Xiangya Hospital of Central South University from January 1, 2023, to December 31, 2023, were enrolled in this study, and their clinical data was also collected. The targeted next-generation sequencing (tNGS) was used to detect Mycoplasma pneumoniae (MP) infection and drug-resistance mutations, and the drug-resistance and treatment in children with MPP were also analyzed. A total of 125 children with pneumonia were involved in this study, including 70 children in the MPP group and 55 children in the bacterial pneumonia group. The results showed that there were 41 boys and 29 girls with an average age of (6.50±3.45) years, with the most common group being the school-age group (age≥6 years). The clinical symptoms were characterized by fever and cough. Laboratory examination showed that the white blood cell and neutrophil counts in the MPP group were lower than those in the bacterial pneumonia group, while the lymphocyte ratio and hemoglobin levels in the MPP group were higher than those in the bacterial pneumonia group, with statistically significant differences (all P<0.05). Twelve children (17.14%) in the MPP group had severe pneumonia, and all children with severe pneumonia had 23Sr RNA A2063G and/or A2064G mutations. The tNGS detected 60 cases of MPP resistance gene mutations, including 59 cases (98.33%) of A2063G mutation in 23Sr RNA and one case (1.67%) of A2064G mutation in 23Sr RNA. There was a significant difference in the positive rate of drug-resistance mutations among patients of different age groups (χ 2=7.991, P=0.021). A total of 63 children (90.00%) with MPP were treated according to the results of drug-resistance mutations, and seven children (70.00%) with MPP without drug-resistance mutations were treated according to the tNGS results. In children with the drug resistance of MPP, 46 cases (95.83%) of non-severe pneumonia and 10 cases (83.33%) of severe pneumonia were treated according to the tNGS results. All patients had a good prognosis, with no deaths reported and a median hospital stay M ( Q1, Q3) of 9 (7, 11) days. In conclusion, MPP is more common in children aged≥6 years old in Hunan Province, and the detection of drug-resistant mutations includes A2063G and A2064G, with A2063G being the main one. The positive rate of drug-resistant mutations is related to age.

OBJECTIVE: To delineate the nature and origin of a chromosomal aberration detected in a boy with mental retardation. METHODS: The proband and his parents were subjected to routine G-banded chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) analysis. RESULTS: The karyotype of the proband was determined as 46, XX, add(8)(p23). No karyotypic abnormality was detected in either of his parents. SNP-array has identified a 34.9 Mb duplication at 8p23.1q11.1 and a 6.78 Mb microdeletion at 8p23.1pter in the proband. No copy number variation was detected in either parent. CONCLUSION The child was diagnosed with 8p inverted duplication deletion syndrome, which might be induced by non-allelic homologous recombination between olfactory genes in the 8p23.1 region.
Child ; Chromosome Banding ; Cytogenetic Analysis ; Genetic Testing ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male

OBJECTIVE: To analyze the clinical and molecular genetic characteristics of patient with Kleefstra syndrome 1. METHODS: Clinical data, chromosomal karyotype and whole genome copy number variations (CNVs) of the patient were analyzed. RESULTS: The patient was found to have a karyotype of 45,XX,-9[4]/46,XX,r(9)(p24q34)[56]. Whole-genome CNVs detection revealed that she has carried a heterozygous deletion of approximately 670 kb at 9q34.3, which encompassed the entire EHMT1 gene. The region is strongly associated with Kleefstra syndrome (1/9q telomere deletion). In addition, the patient also had heterozygous deletion of 9pter, which may predispose to formation of ring chromosome 9. CONCLUSION The child was diagnosed with Kleefstra syndrome type 1 in conjunct with ring chromosome 9.
Child ; Chromosome Deletion ; Chromosomes, Human, Pair 9 ; genetics ; Craniofacial Abnormalities ; genetics ; DNA Copy Number Variations ; Female ; Heart Defects, Congenital ; genetics ; Humans ; Intellectual Disability ; genetics ; Ring Chromosomes

OBJECTIVE: To analyze the clinical and molecular genetics features of a family affected with Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS). METHODS: High-throughput sequencing was used to detect copy number variations (CNVs) and pathogenic variant within the whole exome of the affected child. RESULTS: No pathogenic CNV was found in the child, while exome sequencing identified a heterozygous c.3367_c.3370delAGAA (p.Arg1123Argfs*6) frameshifting variant in the exon 16 of the KAT6B gene. The same variant was not found in either parent. CONCLUSION The c.3367_c.3370delAGAA (p.R1123Rfs*6) probably underlies the disease in the affected child. Above finding has facilitated genetic counseling and prenatal diagnosis for the family.
Blepharophimosis ; genetics ; Child ; Congenital Hypothyroidism ; genetics ; DNA Copy Number Variations ; Facies ; Female ; Heart Defects, Congenital ; genetics ; Histone Acetyltransferases ; genetics ; Humans ; Intellectual Disability ; genetics ; Joint Instability ; genetics ; Mutation ; Phenotype ; Pregnancy

A 76?year?old female patient complained of right chest pain for three months. CT scan showed a clump?like high?density shadow measuring 4.8 cm × 3.0 cm in size in the dorsal portion of the right lower lobe of the lung. Aspiration biopsy was performed, and biopsy samples were subjected to fungal culture and histopathological examination. Histopathological examination showed chronic granulomatous inflammation with hyaline septate hyphae. After 4?day culture, white villous dense colonies were formed on the Sabouraud′s agar medium. The center of the colonies was slightly elevated with wrinkles or radiating striae on the surface, and the bottom of the colonies was faint yellow in color. Microculture yielded abundant septate branched hyphae, and very few colorless hyaline quasi?circular spores. DNA sequencing of rDNA internal transcribed spacer (ITS) regions and β?tubulin genes was performed to identify the isolate, and antifungal susceptibility testing was carried out in vitro. The MEGA7.0 software was used to build phylogenetic trees of Aspergillus fumigatus complex and its closely related species. The isolate was identified as Aspergillus fumigatus by molecular biologic sequencing. The patient was diagnosed with pulmonary aspergilloma. After administration of itraconazole oral solution and vorionazole tablets, the condition got better obviously.