OBJECTIVE: To investigate the clinical manifestations and genetic etiology of a fetus with Neurodevelopmental disorders with deformed facial features and distal skeletal abnormalities (NEDDFSA). METHODS: Clinical data of a NEDDFSA fetus diagnosed at the Affiliated Women and Children's Hospital Affiliated to Ningbo University in March 2025 was selected as the study subject. Whole-exome sequencing (WES) was carried out on the amniotic fluid and parental peripheral blood samples, and candidate variants was verified by Sanger sequencing. The pathogenicity of candidate variant was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: EC2023-094). RESULTS: At 30 weeks of gestation, the fetus was found to have microcephaly, short femur and intrauterine growth restriction. WES revealed that the fetus harbored a de novo heterozygous frameshift variant c.2633dup (p.Gly879ArgfsTer22) of the ZMIZ1 gene, which was rated as pathogenic (PM2_Supporting+PS2_Supporting+PVS1). Combined with 25 cases from the literature, the main manifestations of patients have included intellectual disability, growth retardation and cranio-limb skeletal dysplasia, albeit without clear genotype-phenotype correlation. CONCLUSION The de novo variant c.2633dup (p.Gly879ArgfsTer22) of the ZMIZ1 gene probably underlay the NEDDFSA in this fetus. Genetic testing has enabled accurate prenatal diagnosis and provided evidence for genetic counseling and reproductive guidance of this family.
Humans ; Female ; Pregnancy ; Neurodevelopmental Disorders/genetics* ; Transcription Factors/genetics* ; Fetus/abnormalities* ; Exome Sequencing ; Prenatal Diagnosis

OBJECTIVE: To explore the genetic characteristics of a fetus affected with Structural heart defects and renal anomalies syndrome (SHDRA). METHODS: A pedigree with SHDRA (fetus and the parents) who had visited the Affiliated Women and Children's Hospital of Ningbo University in April 2023 was selected as the study subject. Clinical data of the family were collected. A total of 10 mL of amniotic fluid cells from the fetus and 5 mL of peripheral blood samples from the parents were collected for genomic DNA extraction. Trio whole-exome sequencing (Trio-WES) was performed, and Sanger sequencing was used to validate candidate variants in the family. The identified variants were classified according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the "ACMG Guidelines). Relevant research literature on SHDRA in domestic and international databases were searched for literature review. This study was approved by the Affiliated Women and Children's Hospital of Ningbo University (Ethics No. EC2023-094). RESULTS: In this family, prenatal ultrasound at 18 weeks of gestation revealed left renal multicystic dysplasia in the fetus. After birth, the infant exhibited an ostium secundum atrial septal defect, patent ductus arteriosus, and left renal multicystic dysplasia. Trio-WES revealed that the fetus had carried c.344dup (p.L116Afs*32) and c.90_104dup (p.Ala31_Ala35dup) compound heterozygous variants in the TMEM260 gene, which were respectively inherited from its father and mother. According to the ACMG guidelines, the c.344dup (p.L116Afs*32) and c.90_104dup (p.Ala31_Ala35dup) variants were classified as pathogenic (PM2_Supporting+PVS1+PP4) and likely pathogenic (PM2_Supporting+PM4+PM3+PP4), respectively. According to the literature search strategy set for this study, a total of 6 literature was retrieved, involving 25 SHDRA patients from 20 families. Together with the patients in this study, there were 14 TMEM260 gene variants, most of which were frameshift variants (7 types) and had located in exons 3, 11 and 13. The main clinical features of SHDRA were congenital heart malformation, renal abnormality and neurodevelopmental abnormality, and there was a lack of genotype-phenotype correlation. CONCLUSION The c.344dup (p.L116Afs*32) and c.90_104dup (p.Ala31_Ala35dup) variants of the TMEM260 gene probably underlay the SHDRA in this family. Above finding has provided a basis for clinical diagnosis and genetic counseling for the family.
Humans ; Female ; Pedigree ; Membrane Proteins/genetics* ; Male ; Heart Defects, Congenital/genetics* ; Kidney/abnormalities* ; Pregnancy ; Adult ; Kidney Diseases/congenital* ; Exome Sequencing ; Mutation ; Genetic Testing

Objective:To explore the genetic characteristics of a fetus affected with Structural heart defects and renal anomalies syndrome (SHDRA).Methods:A pedigree with SHDRA (fetus and the parents) who had visited the Affiliated Women and Children′s Hospital of Ningbo University in April 2023 was selected as the study subject. Clinical data of the family were collected. A total of 10 mL of amniotic fluid cells from the fetus and 5 mL of peripheral blood samples from the parents were collected for genomic DNA extraction. Trio whole-exome sequencing (Trio-WES) was performed, and Sanger sequencing was used to validate candidate variants in the family. The identified variants were classified according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the " ACMG Guidelines). Relevant research literature on SHDRA in domestic and international databases were searched for literature review. This study was approved by the Affiliated Women and Children′s Hospital of Ningbo University (Ethics No. EC2023-094).Results:①In this family, prenatal ultrasound at 18 weeks of gestation revealed left renal multicystic dysplasia in the fetus. After birth, the infant exhibited an ostium secundum atrial septal defect, patent ductus arteriosus, and left renal multicystic dysplasia. Trio-WES revealed that the fetus had carried c. 344dup(p.L116Afs*32) and c. 90_104dup(p.Ala31_Ala35dup) compound heterozygous variants in the TMEM260 gene, which were respectively inherited from its father and mother. According to the ACMG guidelines, the c. 344dup(p.L116Afs*32) and c. 90_104dup (p.Ala31_Ala35dup) variants were classified as pathogenic (PM2_Supporting+ PVS1+ PP4) and likely pathogenic (PM2_Supporting+ PM4+ PM3+ PP4), respectively. ②According to the literature search strategy set for this study, a total of 6 literature was retrieved, involving 25 SHDRA patients from 20 families. Together with the patients in this study, there were 14 TMEM260 gene variants, most of which were frameshift variants (7 types) and had located in exons 3, 11 and 13. The main clinical features of SHDRA were congenital heart malformation, renal abnormality and neurodevelopmental abnormality, and there was a lack of genotype-phenotype correlation. Conclusion:The c. 344dup(p.L116Afs*32) and c. 90_104dup(p.Ala31_Ala35dup) variants of the TMEM260 gene probably underlay the SHDRA in this family. Above finding has provided a basis for clinical diagnosis and genetic counseling for the family.

Objective:To evaluate the effectiveness of anti-G straining maneuver (AGSM) in pilots by surface electromyography (sEMG), and to explore the relationships between characteristics of sEMG and anti-G endurance in pilots.Methods:Thirty-eight male high-performance fighter pilots who completed the human centrifuge test at the Air Force Medical Center were selected. Among them, 25 completed the 8.0 G for 10 s anti-G endurance test and 13 completed the 9.0 G for 10 s anti-G endurance test. The sEMG tester was used to keep track of the changes of sEMG in rectus abdominis, rectus femoris, anterior tibial and gastrocnemius muscles while pilots were engaged in AGSM. The anti-G endurance was evaluated according to the changes of visual fields and consciousness. The pilots were divided into 3 groups: the good vision and consciousness group, peripheral visual field narrowing group and endurance endpoint group. The differences in the integral electromyogram (iEMG), mean power frequency (MPF) and muscle input rates between the 3 groups were investigated.Results:A total of 25 pilots completed the 8.0 G for 10 s anti-G endurance test. Among them, 8 (32.0%) were in the good vision and consciousness group, 13 (52.0%) in the peripheral visual field narrowing group and 4 (16.0%) reached the endurance endpoint. Among the 13 pilots who completed the 9.0 G for 10 s anti-G endurance test, 3 (23.1%) were in the good vision and consciousness group, 6 (46.1%) in the peripheral visual field narrowing group, and 4 (30.8%) in the endurance endpoint group. The results of sEMG showed that the iEMG values of the anterior tibialis muscle in pilots under the 9.0 G for 10 s load were significantly different across endurance groups ( H=7.54, P=0.023), and that the iEMG values of the tibialis anterior muscle in the good vision and consciousness group were higher than those in the endurance endpoint group ( P=0.036). The negative slopes of MPF for the rectus abdominis, rectus femoris, anterior tibialis, and gastrocnemius muscles were higher in the good vision and consciousness group than in the other 2 groups, but the differences were not statistically significant ( P>0.05). During the 8.0 G for 10 s anti-G endurance test, there were significant differences in lower limb muscle contribution rates between the 3 groups ( F=4.19, P=0.029). The endurance endpoint group exhibited a lower contribution rate than the good vision and consciousness group ( P=0.025). During the 9.0 G for 10 s anti-G endurance test, there were significant differences in tibialis anterior muscle contribution rates between the 3 groups ( F=4.16, P=0.049). The endurance endpoint group demonstrated a lower contribution rate than the good vision and consciousness group ( P=0.049). Conclusions:The full and balanced activation of abdominal muscles and lower limb muscles, especially the effective mobilization of calf muscles, plays a pivotal role in improving pilots′ AGSM efficiency in high G environments.

Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

By reviewing the practice and current situation of the standardized training for naval surgical residents,in combination with the practice of the standardized training for resident doctors in Shanghai,this paper sums up the existing experience and explores clinical teaching,management and patterns of standardized training for naval residents based on the post competence.The aim of the study is to strengthen naval primary medical care,enhance trainees'working competence and medical support capabilities,improve the quality and level of standardized training for naval residents,so as to provide reference for the further development of the training strategy of naval officers.

Objective: To understand the health status of primary school freshmen in Guiyang and the health management service needs of parents after examination, so as to provide a reference for establishment of a collaborative health management framework involving schools, families, and healthcare providers. Methods: From September to October 2024, a stratified random cluster sampling method was used in Guiyang City to select 3 210 students and 3 133 parents who participated in the physical examination for primary school freshmen. Demographic indicators, physical examination indicators and laboratory examination indicators of students were collected, and parents needs for post examination health management service were investigated by self designed questionnaire. Multiple linear regression analysis was adopted to investigate the related factors of parents health management service needs after the examination. Results: The detection rates of common illness among primary school freshmen were 60.22% for dental caries, 17.23 % for screening myopia, 6.11% for obesity, 3.86% for iron deficiency anemia, and 1.15% for scoliosis. The co-occurrence rate of common illness among freshmen during the physical examination was 23.89% ( n =767), among which the comorbidity rate of screening myopia and dental caries (8.22%) and obesity and dental caries (4.27%) were higher. About 63.80% parents indicated that the physical examination items were simple, and 2 366 parents (75.52%) indicated a demand for post examination management services; the average score of parents demands for post examination services was (3.12±0.70). In terms of the scores of each dimension, the mean score of nutrition and health (3.58±0.74) was the highest, while the lowest mean score was for traditional Chinese medicine health care (2.77±0.67). The mean scores for the other dimensions were as follows:exercise intervention (3.29± 0.79 ), psychological monitoring (3.17±0.58), and health education and signing (2.81±0.73). The results of multiple linear regression analysis showed that parents educational level (junior high school, high school/vocational school, college/undergraduate and above), living conditions (floating), and children s illness status (1, 2, >3 types) were the related factors of parents health management service needs after the entrance examination for new students ( B =2.16, 3.07, 3.68; -2.19; 3.14, 3.34, 3.11, P <0.05). Conclusions The prevalence of common illness in primary schools in Guiyang is characterized by a heavy burden from single diseases, with a notable occurrence of multiple comorbidities. After the physical examination, parents have obvious demand for follow up health management services. These health management services should integrate the concept of multi disease prevention according to the needs of parents.

Objective:This study aims to analyze the performance of five automatic cell type annotation methods in single cell RNA sequencing (scRNA-seq) data.Methods:Simulated data were generated using the Splatter package in R language, taking into account two data characteristics: the number of cells and the number of genes. The actual data came from the GSE10245 scRNA seq dataset of non-small cell lung cancer in Gene Expression Omnibus (GEO) database, the data had been pre-processed and batch effects had been eliminated. The automatic cell type recognition (ACTINN) of neural networks, the single-cell type annotation method based on deep learning (scDeepSort), the reference batch transcriptome annotation scRNA seq R-package (SingleR), the cross platform and cross species scRNA seq data classifier (SingleCellNet), and the cross scRNA seq dataset projection (scMap-cell) were implemented using the Tensorflow library in Python. The performance evaluation indicators for cell type annotation included accuracy (ACC), F1-score, and Matthews correlation coefficient (MCC). Each method was validated using ten fold cross validation, and the average value was taken after 50 repeated runs for performance comparison between methods. The Dunnett's t-test in the DescTools package of R language was used for multiple comparisons between ACTINN and other four methods. Results:Under 12 different scenarios (3 levels of cell numbers × 4 levels of gene numbers), simulated data analysis showed that compared with scDeepSort, SingleR, SingleCellNet, and scMap-cell, the percentage increase in ACC value of ACTINN ranged from 3.31% to 14.59%, 1.38% to 13.03%, 12.98% to 25.25%, and 20.72% to 29.62%, respectively; the range of F1 score improvement percentages were 2.75% - 22.74%, 2.46% - 23.68%, 5.07% - 27.47%, and 10.27% - 31.47%, respectively; the percentage increase ranges for MCC values were 3.42% - 9.75%, 2.26% - 7.61%, 5.41% - 11.11%, and 8.27% - 15.22%, respectively. Actual data analysis showed that the ACC value of ACTINN was 81.0%, which was increased by 2.1%, 5.2%, 7.9%, and 8.9% compared with the above four methods, respectively; the F1-score value was 80.5%, which was increased by 2.3%, 5.9%, 2.4%, and 6.0%, respectively; the MCC value was 83.3%, which was increased by 0.9%, 2.5%, 3.4%, and 11.2%, respectively. The results of Dunnett's t-test showed that the difference was not statistically significant in ACC values between scDeepSort and ACTINN ( P = 0.821), in F1-score values between scDeepSort and ACTINN ( P = 0.498), and in MCC values between scDeepSort, SingleCellNet and ACTINN ( P = 0.904, 0.134). However, the differences were statistically significant in other multiple comparisons ( P < 0.05). Conclusions:ACTINN and scDeepSort have good performance in cell type annotation, with ACTINN showing outstanding performance and SingleR showing robust performance, while SingleCellNet and scMap-cell have relatively limited performance. This suggests that self-attention mechanism algorithm based on Transformer framework is expected to promote further development of automatic cell annotation methods.

Objective:This study aims to analyze the performance of five automatic cell type annotation methods in single cell RNA sequencing (scRNA-seq) data.Methods:Simulated data were generated using the Splatter package in R language, taking into account two data characteristics: the number of cells and the number of genes. The actual data came from the GSE10245 scRNA seq dataset of non-small cell lung cancer in Gene Expression Omnibus (GEO) database, the data had been pre-processed and batch effects had been eliminated. The automatic cell type recognition (ACTINN) of neural networks, the single-cell type annotation method based on deep learning (scDeepSort), the reference batch transcriptome annotation scRNA seq R-package (SingleR), the cross platform and cross species scRNA seq data classifier (SingleCellNet), and the cross scRNA seq dataset projection (scMap-cell) were implemented using the Tensorflow library in Python. The performance evaluation indicators for cell type annotation included accuracy (ACC), F1-score, and Matthews correlation coefficient (MCC). Each method was validated using ten fold cross validation, and the average value was taken after 50 repeated runs for performance comparison between methods. The Dunnett's t-test in the DescTools package of R language was used for multiple comparisons between ACTINN and other four methods. Results:Under 12 different scenarios (3 levels of cell numbers × 4 levels of gene numbers), simulated data analysis showed that compared with scDeepSort, SingleR, SingleCellNet, and scMap-cell, the percentage increase in ACC value of ACTINN ranged from 3.31% to 14.59%, 1.38% to 13.03%, 12.98% to 25.25%, and 20.72% to 29.62%, respectively; the range of F1 score improvement percentages were 2.75% - 22.74%, 2.46% - 23.68%, 5.07% - 27.47%, and 10.27% - 31.47%, respectively; the percentage increase ranges for MCC values were 3.42% - 9.75%, 2.26% - 7.61%, 5.41% - 11.11%, and 8.27% - 15.22%, respectively. Actual data analysis showed that the ACC value of ACTINN was 81.0%, which was increased by 2.1%, 5.2%, 7.9%, and 8.9% compared with the above four methods, respectively; the F1-score value was 80.5%, which was increased by 2.3%, 5.9%, 2.4%, and 6.0%, respectively; the MCC value was 83.3%, which was increased by 0.9%, 2.5%, 3.4%, and 11.2%, respectively. The results of Dunnett's t-test showed that the difference was not statistically significant in ACC values between scDeepSort and ACTINN ( P = 0.821), in F1-score values between scDeepSort and ACTINN ( P = 0.498), and in MCC values between scDeepSort, SingleCellNet and ACTINN ( P = 0.904, 0.134). However, the differences were statistically significant in other multiple comparisons ( P < 0.05). Conclusions:ACTINN and scDeepSort have good performance in cell type annotation, with ACTINN showing outstanding performance and SingleR showing robust performance, while SingleCellNet and scMap-cell have relatively limited performance. This suggests that self-attention mechanism algorithm based on Transformer framework is expected to promote further development of automatic cell annotation methods.

Objective:To explore the genetic characteristics of a fetus affected with Structural heart defects and renal anomalies syndrome (SHDRA).Methods:A pedigree with SHDRA (fetus and the parents) who had visited the Affiliated Women and Children′s Hospital of Ningbo University in April 2023 was selected as the study subject. Clinical data of the family were collected. A total of 10 mL of amniotic fluid cells from the fetus and 5 mL of peripheral blood samples from the parents were collected for genomic DNA extraction. Trio whole-exome sequencing (Trio-WES) was performed, and Sanger sequencing was used to validate candidate variants in the family. The identified variants were classified according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the " ACMG Guidelines). Relevant research literature on SHDRA in domestic and international databases were searched for literature review. This study was approved by the Affiliated Women and Children′s Hospital of Ningbo University (Ethics No. EC2023-094).Results:①In this family, prenatal ultrasound at 18 weeks of gestation revealed left renal multicystic dysplasia in the fetus. After birth, the infant exhibited an ostium secundum atrial septal defect, patent ductus arteriosus, and left renal multicystic dysplasia. Trio-WES revealed that the fetus had carried c. 344dup(p.L116Afs*32) and c. 90_104dup(p.Ala31_Ala35dup) compound heterozygous variants in the TMEM260 gene, which were respectively inherited from its father and mother. According to the ACMG guidelines, the c. 344dup(p.L116Afs*32) and c. 90_104dup (p.Ala31_Ala35dup) variants were classified as pathogenic (PM2_Supporting+ PVS1+ PP4) and likely pathogenic (PM2_Supporting+ PM4+ PM3+ PP4), respectively. ②According to the literature search strategy set for this study, a total of 6 literature was retrieved, involving 25 SHDRA patients from 20 families. Together with the patients in this study, there were 14 TMEM260 gene variants, most of which were frameshift variants (7 types) and had located in exons 3, 11 and 13. The main clinical features of SHDRA were congenital heart malformation, renal abnormality and neurodevelopmental abnormality, and there was a lack of genotype-phenotype correlation. Conclusion:The c. 344dup(p.L116Afs*32) and c. 90_104dup(p.Ala31_Ala35dup) variants of the TMEM260 gene probably underlay the SHDRA in this family. Above finding has provided a basis for clinical diagnosis and genetic counseling for the family.