OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a pediatric child with RELA-associated autoinflammatory disease (RAID) caused by a RELA gene variant, and to review the reported cases in the literature. METHODS: A pediatric child with RAID who presented with recurrent fever, vomiting, and oral ulcers for over 5 years was selected as the study subject. The child visited the Women and Children's Hospital of Ningbo University in August 2023. Clinical data were collected, and peripheral blood samples were obtained from the child and his family members for whole-exome sequencing (WES) and Sanger sequencing to identify and validate candidate variants. The pathogenicity of the variants was analyzed accordingly. Using the keywords "RELA" "NF-κB" "autoinflammatory disease" "tofacitinib" "sulfasalazine" a literature search was conducted in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed from January 1, 2000 to December 13, 2023. This study was approved by the Medical Ethics Committee of the Women and Children's Hospital of Ningbo University (Ethics No. EC2020-048). RESULTS: The child primarily manifested with recurrent fever, vomiting, and oral ulcers. WES identified a heterozygous nonsense variant c.985C>T (p.Arg329Ter) in the RELA gene, which was inherited from the mother. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants and the Clinical Genome Resource (ClinGen) recommendations for PVS1, this variant was classified as pathogenic (PVS1+PM2_Supporting+PP4). Despite treatment with adalimumab and tocilizumab, the child's symptoms persisted. Switching to tofacitinib improved oral ulcers, but fever and vomiting continued. The addition of thalidomide significantly alleviated fever and vomiting, and the patient's growth and development remained normal. A literature review identified 14 unrelated RAID families, including a total of 35 cases (including the present child). The main clinical features were recurrent oral ulcers, genital ulcers, skin problems, fever, diarrhea, abdominal pain, and vomiting. CONCLUSION The nonsense variant c.985C>T (p.Arg329Ter) in the RELA gene is likely the genetic cause of the child's recurrent fever, vomiting, and oral ulcers. WES is valuable for timely diagnosis of RAID and provides a basis for clinical treatment strategies.
Humans ; Male ; Transcription Factor RelA/genetics* ; Female ; Hereditary Autoinflammatory Diseases/genetics* ; Child ; Pedigree ; Exome Sequencing

Objective:To explore the clinical phenotype and genetic characteristics of a pediatric child with RELA-associated autoinflammatory disease (RAID) caused by a RELA gene variant, and to review the reported cases in the literature. Methods:A pediatric child with RAID who presented with recurrent fever, vomiting, and oral ulcers for over 5 years was selected as the study subject. The child visited the Women and Children′s Hospital of Ningbo University in August 2023. Clinical data were collected, and peripheral blood samples were obtained from the child and his family members for whole exome sequencing (WES) and Sanger sequencing to identify and validate candidate variants. The pathogenicity of the variants was analyzed accordingly. Using the keywords " RELA" " NF-κB" " autoinflammatory disease" " tofacitinib" " sulfasalazine" a literature search was conducted in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed from January 1, 2000 to December 13, 2023. This study was approved by the Medical Ethics Committee of the Women and Children′s Hospital of Ningbo University (Ethics No. EC2020-048).Results:① The child primarily manifested with recurrent fever, vomiting, and oral ulcers. ② WES identified a heterozygous nonsense variant c. 985C>T (p.Arg329Ter) in the RELA gene, which was inherited from the mother. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants and the Clinical Genome Resource (ClinGen) recommendations for PVS1, this variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP4). ③ Despite treatment with adalimumab and tocilizumab, the child′s symptoms persisted. Switching to tofacitinib improved oral ulcers, but fever and vomiting continued. The addition of thalidomide significantly alleviated fever and vomiting, and the patient′s growth and development remained normal. ④ A literature review identified 14 unrelated RAID families, including a total of 35 cases (including the present child). The main clinical features were recurrent oral ulcers, genital ulcers, skin problems, fever, diarrhea, abdominal pain, and vomiting. Conclusion:The nonsense variant c. 985C>T (p.Arg329Ter) in the RELA gene is likely the genetic cause of the child′s recurrent fever, vomiting, and oral ulcers. WES is valuable for timely diagnosis of RAID and provides a basis for clinical treatment strategies.

Objective:To explore the effects of smoking on peripheral regulatory T cells (Tregs), transforming growth factor beta1 (TGF-β 1) and interleukin-10 (IL-10) in elderly patients with non-small cell lung cancer (NSCLC). Methods:This was a cross-sectional study. A total of 43 elderly patients (≥60 years old) who were hospitalized in the Department of Geriatrics Medicine, Guangzhou First People′s Hospital from January 2018 to December 2024 and were newly diagnosed with NSCLC were recruited. According to smoking history, patients were divided into non-smoking group (15 cases), low smoking group (13 cases, smoking index<400) and high smoking group (15 cases, smoking index≥400). Venous blood samples were collected from participants, plasma and cells were separated. Flow cytometry was used to measure the proportions of Tregs and the expression of forkhead box P3 (Foxp3) in peripheral blood. Plasma levels of TGF-β 1 and IL-10 were measured by enzyme-linked immunosorbent assay. The effects of smoking on peripheral Tregs, TGF-β 1, and IL-10 in elderly patients with NSCLC were analyzed. Data were analyzed by one-way ANOVA, rank-sum test, and Fisher′s exact test. Results:The proportions of Tregs in non-smoking group, low smoking group and high smoking group were 2.50% (2.32%, 2.81%), 2.83% (2.48%, 3.72%), and 3.01% (2.37%, 3.73%), respectively, and there were no statistically significant differences among the three groups ( H=3.845, P>0.05). The proportions of Foxp3 +Tregs were (3.72±0.84)%, (4.64±1.10)%, and (4.68±1.27%), respectively. The mean fluorescence intensities (MFI) of Foxp3 were 123.0 (108.0, 128.0), 131.0 (123.5, 350.0), and 222.0 (141.0, 311.0), respectively. Both the proportions of Foxp3 +Tregs and the MFI of Foxp3 were higher in low smoking group and high smoking group than those in non-smoking group (all P<0.05). However, there were no significant differences between low smoking group and high smoking group (all P>0.05). The concentrations of IL-10 were 2.27 (1.42, 3.95), 3.42 (2.30, 5.08), and 3.26 (2.35, 6.28) ng/L, respectively. There were no statistically significant differences among the three groups ( H=2.930, P>0.05). The concentrations of TGF-β 1 were (10.72±9.37), (13.46±10.39), and (25.28±16.67) ng/ml, respectively. The concentration of TGF-β 1 in high smoking group was higher than that in non-smoking group and low smoking group (all P<0.05). However, there was no statistically significant difference between low smoking group and non-smoking group ( P>0.05). Conclusions:Smoking intensity may be correlated with the immunosuppressive function of Tregs in elderly patients with NSCLC. Higher smoking levels are associated with increased Foxp3 expression in Tregs and elevated plasma levels of TGF-β 1, potentially enhancing the immunosuppressive function of Tregs.

Objective:To study the feasibility of detecting vertical semicircular canal function and to analyze the three-dimensional(3D)characteristics and normal reference value in healthy young people.Methods:This was a cross-sectional study conducted from January to June 2024. A three-axis rotating chair was used to perform vertical sinusoidal rotation on 52 healthy young adults (26 males and 26 females, aged 18-40 years) in the left anterior-right posterior (LARP) and right anterior-left posterior (RALP) semicircular canal planes. For each plane, nystagmus was induced with six combinations of different angles and velocity front and back rotation angles of ±30°,±60°,±90°, and velocities of 40°/s and 80°/s, the slow phase velocity (SPV) and their symmetry of 3D nystagmus were analyzed. SPSS 20.0 was used to compare the statistical differences in these two parameters across different stimulation protocols.Results:There were no spontaneous nystagmus in the 52 subjects, and all tests were finished. Except the combinations of (±30°-40°/s), three components of nystagmus were induced stably in the rest of the stimulations. The SPVs of vertical components were no statistically insignificant ( P>0.05), and some horizontal or torsion components were statistically significant ( P<0.05). The 95% reference range of the symmetry was≤25% in the vertical and≤30% in the torsional component of the nystagmus except for (±30°-80°/s), the symmetry was 32.2% and 49.2% respectively. The trend changes of the three components were consistent, among which the vertical and torsional components induced by (±60°-80°/s) and (±90°-80°/s) were the best, the SPV value of the vertical components was higher in the latter group than the former apart from the front RALP, while no significant difference was found in the torsional components ( P>0.05). Conclusion:The (±90°-80°/s) combination is the optimal method to detect the function of vertical semicircular canal in 3D chair test. When observing torsional component, the combining scheme of (±60°-80°/s) and (±90°-80°/s) is better. Considering tolerance, the (±60°-80°/s) combination is recommended.

Growth factors (GFs) are a class of peptides that facilitate cell growth by binding to specific receptors on the cell membrane. With unique properties, GFs are widely applied in the repair of injured tissue. To address the limitations associated with natural peptide-based GFs and recombinant GFs, researchers have developed diverse GF mimetics. This article offers a comprehensive review on common types of GFs and their applications in tissue repair and summarizes the features of GF mimetics currently under development. The aim is to provide valuable references for promoting the application of GFs in regenerative medicine.
Intercellular Signaling Peptides and Proteins/therapeutic use* ; Humans ; Tissue Engineering/methods* ; Regenerative Medicine/methods* ; Animals ; Wound Healing/drug effects* ; Biomimetic Materials

Objective To explore the role of ocular vestibular evoked myogenic potential (oVEMP) and unilateral centrifugation subjective visual vertical (UC-SVV) tests in evaluating the utricular function of patients with Meniere’s disease (MD) at different clinical stages. Methods A total of 97 unilateral MD patients at Shandong Provincial ENT Hospital from July 2019 to September 2021 were selected. All patients underwent oVEMP, UC-SVV, and pure tone audiometry tests. MD patients were classified into clinical stages 1, 2, 3, and 4, with stages 1 and 2 defined as early stage and stages 3 and 4 as late stage. The results of utricular function tests (abnormal rates of oVEMP, UC-SVV, and oVEMP＋UC-SVV) were compared among patients at different stages. Spearman correlation analysis was used to evaluate the correlation between utricular function and clinical staging. Results Among the 97 MD patients, the abnormal rate of oVEMP was 66.0% (64/97), and the abnormal rate of UC-SVV was 55.7% (54/97). The abnormal rates of oVEMP and oVEMP＋UC-SVV in early-stage patients were significantly lower than those in late-stage patients (P＜0.05), while the difference in UC-SVV abnormal rates between the two groups was not statistically significant. Intra-group comparisons showed that the abnormal rate of oVEMP＋UC-SVV in stage 1 patients was significantly lower than that in stage 2 patients (P＜0.05), without significant difference in the other indices. There were no significant differences among the three indices in stages 3 and 4 patients. Spearman correlation test results indicated that the abnormal rate of oVEMP (r＝0.336, P＝0.001) and the abnormal rate of oVEMP＋UC-SVV (r＝0.301, P＝0.003) were weakly positively correlated with clinical staging, while there was no correlation between the abnormal rate of UC-SVV and clinical staging (r＝0.022, P＝0.832). Conclusions Both oVEMP and UC-SVV tests can assess utricular function in MD patients at different clinical stages. Their combination is helpful of early-stage (stages 1 and 2) MD diagnosis.

Objective:To explore the clinical phenotype and genetic characteristics of a pediatric child with RELA-associated autoinflammatory disease (RAID) caused by a RELA gene variant, and to review the reported cases in the literature. Methods:A pediatric child with RAID who presented with recurrent fever, vomiting, and oral ulcers for over 5 years was selected as the study subject. The child visited the Women and Children′s Hospital of Ningbo University in August 2023. Clinical data were collected, and peripheral blood samples were obtained from the child and his family members for whole exome sequencing (WES) and Sanger sequencing to identify and validate candidate variants. The pathogenicity of the variants was analyzed accordingly. Using the keywords " RELA" " NF-κB" " autoinflammatory disease" " tofacitinib" " sulfasalazine" a literature search was conducted in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed from January 1, 2000 to December 13, 2023. This study was approved by the Medical Ethics Committee of the Women and Children′s Hospital of Ningbo University (Ethics No. EC2020-048).Results:① The child primarily manifested with recurrent fever, vomiting, and oral ulcers. ② WES identified a heterozygous nonsense variant c. 985C>T (p.Arg329Ter) in the RELA gene, which was inherited from the mother. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants and the Clinical Genome Resource (ClinGen) recommendations for PVS1, this variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP4). ③ Despite treatment with adalimumab and tocilizumab, the child′s symptoms persisted. Switching to tofacitinib improved oral ulcers, but fever and vomiting continued. The addition of thalidomide significantly alleviated fever and vomiting, and the patient′s growth and development remained normal. ④ A literature review identified 14 unrelated RAID families, including a total of 35 cases (including the present child). The main clinical features were recurrent oral ulcers, genital ulcers, skin problems, fever, diarrhea, abdominal pain, and vomiting. Conclusion:The nonsense variant c. 985C>T (p.Arg329Ter) in the RELA gene is likely the genetic cause of the child′s recurrent fever, vomiting, and oral ulcers. WES is valuable for timely diagnosis of RAID and provides a basis for clinical treatment strategies.

Objective:To explore the effects of smoking on peripheral regulatory T cells (Tregs), transforming growth factor beta1 (TGF-β 1) and interleukin-10 (IL-10) in elderly patients with non-small cell lung cancer (NSCLC). Methods:This was a cross-sectional study. A total of 43 elderly patients (≥60 years old) who were hospitalized in the Department of Geriatrics Medicine, Guangzhou First People′s Hospital from January 2018 to December 2024 and were newly diagnosed with NSCLC were recruited. According to smoking history, patients were divided into non-smoking group (15 cases), low smoking group (13 cases, smoking index<400) and high smoking group (15 cases, smoking index≥400). Venous blood samples were collected from participants, plasma and cells were separated. Flow cytometry was used to measure the proportions of Tregs and the expression of forkhead box P3 (Foxp3) in peripheral blood. Plasma levels of TGF-β 1 and IL-10 were measured by enzyme-linked immunosorbent assay. The effects of smoking on peripheral Tregs, TGF-β 1, and IL-10 in elderly patients with NSCLC were analyzed. Data were analyzed by one-way ANOVA, rank-sum test, and Fisher′s exact test. Results:The proportions of Tregs in non-smoking group, low smoking group and high smoking group were 2.50% (2.32%, 2.81%), 2.83% (2.48%, 3.72%), and 3.01% (2.37%, 3.73%), respectively, and there were no statistically significant differences among the three groups ( H=3.845, P>0.05). The proportions of Foxp3 +Tregs were (3.72±0.84)%, (4.64±1.10)%, and (4.68±1.27%), respectively. The mean fluorescence intensities (MFI) of Foxp3 were 123.0 (108.0, 128.0), 131.0 (123.5, 350.0), and 222.0 (141.0, 311.0), respectively. Both the proportions of Foxp3 +Tregs and the MFI of Foxp3 were higher in low smoking group and high smoking group than those in non-smoking group (all P<0.05). However, there were no significant differences between low smoking group and high smoking group (all P>0.05). The concentrations of IL-10 were 2.27 (1.42, 3.95), 3.42 (2.30, 5.08), and 3.26 (2.35, 6.28) ng/L, respectively. There were no statistically significant differences among the three groups ( H=2.930, P>0.05). The concentrations of TGF-β 1 were (10.72±9.37), (13.46±10.39), and (25.28±16.67) ng/ml, respectively. The concentration of TGF-β 1 in high smoking group was higher than that in non-smoking group and low smoking group (all P<0.05). However, there was no statistically significant difference between low smoking group and non-smoking group ( P>0.05). Conclusions:Smoking intensity may be correlated with the immunosuppressive function of Tregs in elderly patients with NSCLC. Higher smoking levels are associated with increased Foxp3 expression in Tregs and elevated plasma levels of TGF-β 1, potentially enhancing the immunosuppressive function of Tregs.

Objective:To study the feasibility of detecting vertical semicircular canal function and to analyze the three-dimensional(3D)characteristics and normal reference value in healthy young people.Methods:This was a cross-sectional study conducted from January to June 2024. A three-axis rotating chair was used to perform vertical sinusoidal rotation on 52 healthy young adults (26 males and 26 females, aged 18-40 years) in the left anterior-right posterior (LARP) and right anterior-left posterior (RALP) semicircular canal planes. For each plane, nystagmus was induced with six combinations of different angles and velocity front and back rotation angles of ±30°,±60°,±90°, and velocities of 40°/s and 80°/s, the slow phase velocity (SPV) and their symmetry of 3D nystagmus were analyzed. SPSS 20.0 was used to compare the statistical differences in these two parameters across different stimulation protocols.Results:There were no spontaneous nystagmus in the 52 subjects, and all tests were finished. Except the combinations of (±30°-40°/s), three components of nystagmus were induced stably in the rest of the stimulations. The SPVs of vertical components were no statistically insignificant ( P>0.05), and some horizontal or torsion components were statistically significant ( P<0.05). The 95% reference range of the symmetry was≤25% in the vertical and≤30% in the torsional component of the nystagmus except for (±30°-80°/s), the symmetry was 32.2% and 49.2% respectively. The trend changes of the three components were consistent, among which the vertical and torsional components induced by (±60°-80°/s) and (±90°-80°/s) were the best, the SPV value of the vertical components was higher in the latter group than the former apart from the front RALP, while no significant difference was found in the torsional components ( P>0.05). Conclusion:The (±90°-80°/s) combination is the optimal method to detect the function of vertical semicircular canal in 3D chair test. When observing torsional component, the combining scheme of (±60°-80°/s) and (±90°-80°/s) is better. Considering tolerance, the (±60°-80°/s) combination is recommended.

Objective:To explore the genetic etiology for a child with Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 6 (PEOA6).Methods:A child who had attended the Women and Children′s Hospital Affiliated to Ningbo University on 7 August, 2023 was selected as the study subject. Clinical data of the child were analyzed retrospectively. The child and her parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis. This study was approved by Medical Ethics Committee of the Women and Children′s Hospital Affiliated to Ningbo University (Ethics No. EC2020-048).Results:The child, a 7-year-old female, had presented with limb muscle pain, amyosthenia, significantly increased creatine kinase, congenital diaphragmatic hernia and recurrent respiratory tract infections. WES revealed that she has harbored a heterozygous c. 1590G>C (p.L530F) variant of the DNA2 gene, which was verified to have a de novo origin by Sanger sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1590G>C was rated as a likely pathogenic variant (PS2+ PM2_Supporting+ PP3). Conclusion:The c.1590G>C (p.L530F) variant of the DNA2 gene probably underlay the PEOA6 in this child.