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

Thyroid cancer (TC) is the most prevalent malignancy of the endocrine system. While most patients achieve favorable prognoses with early treatment, patients with advanced TC face a scarcity of effective therapeutic strategies. The thyroid gland is one of the most immunogenic tissues in the human body. With the deepening understanding of immune evasion mechanisms in TC and the application of immunotherapy in various solid malignancies, immune checkpoint therapy for TC has shown considerable therapeutic potential, offering new hope for patients with advanced TC. This paper focuses on summarizing the latest advancements in immune checkpoint therapy for TC, aiming to provide new directions for future research.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Thyroid cancer (TC) is the most prevalent malignancy of the endocrine system. While most patients achieve favorable prognoses with early treatment, patients with advanced TC face a scarcity of effective therapeutic strategies. The thyroid gland is one of the most immunogenic tissues in the human body. With the deepening understanding of immune evasion mechanisms in TC and the application of immunotherapy in various solid malignancies, immune checkpoint therapy for TC has shown considerable therapeutic potential, offering new hope for patients with advanced TC. This paper focuses on summarizing the latest advancements in immune checkpoint therapy for TC, aiming to provide new directions for future research.

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.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

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

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 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 investigate the clinical value of targeted sequencing panel in the detection of genetic variation in neonates in neonatal intensive care unit (NICU).Methods:All neonates (≤28 d of age) admitted in the NICU (case group) and 200 full-term healthy neonates born with no obvious phenotypic abnormalities of Huzhou Maternity and Child Health Care Hospital were enrolled in this prospective study from November 2022 to January 2023. Based on a list of preventable and treatable rare diseases as well as newly screened diseases in China, a targeted sequencing panel suitable for Chinese newborns was designed to target the pathogenic genes and mutation sites associated with 601 genes and 542 diseases. Dried blood spot specimens were prepared and analyzed by the targeted sequencing panel. Pathogenic sites detected by the panel sequencing were verified using Sanger sequencing. The genetic testing results were analyzed according to the clinical features of the neonates. According to the number of primary clinical diagnosis index (including premature infants, neonatal hyperbilirubinemia, hemorrhagic diseases, neonatal infections, ventricular septal defect/patent ductus arteriosus, and others), these patients were divided into four groups with 1, 2, 3, and ≥4 diagnosis index, respectively. Chi-square test and linear correlation Chi-square test were used for statistical analysis. Results:There were 173 patients in the case group and 30.6% (53/173) of them carried pathogenic variants, including 52 positive for pathogenic genes and one with chromosome copy number variant. The positive rate of pathogenic genes was significantly higher in the case group than in the control group [30.1% (52/173) vs. 15.0% (30/200), χ 2=12.26, P<0.001]. Fourteen pathogenic genes were detected in the case group, including FLG, UGT1A1, G6PD, MYH7, AR, ABCC2, ACADS, CYP21A2, GJB2, MEFV, PAH, PKHD1, SCN4A, and HBA. In the case group, the detection rate of pathogenic variants in jaundiced neonates was higher than that in non-jaundiced neonates [35.2% (44/125) vs. 18.8% (9/48), χ 2=4.42, P=0.036]. However, there were no statistically significant differences in the detection rates of pathogenic variants between male and female infants, infants born to mothers of advanced maternal age or not, infants born to mothers with or without gestational diabetes mellitus, premature and term infants, or infants with or without hemorrhagic disorders, neonatal infections, or ventricular septal defects/patent ductus arteriosus in the case group (all P>0.05). The detection rate of pathogenic variants showed a linear increase in infants with 1, 2, 3, and ≥4 diagnosis index [21.1% (8/38), 25.4% (15/59), 38.2% (13/34), and 40.5% (17/42); linear correlation χ 2=4.84, P=0.028]. In the case group, seven genes with a high detection rate of genetic variation (including positive pathogenic genes and carriers) were UGT1A1 [had the highest detection rate, 24.9% (43/173)], GJB2, FLG, DUOX2, ABCA4, G6PD, and MUT. Seven loci with higher mutation frequency were c.211G>A(p.Gly71Arg), c.1091C>T(p.Pro364Leu), c.-41_-40dupTA, and c.686C>A(p.Pro229Gln) in the UGT1A1 gene, c.109G>A(p.Val37Ile) in the GJB2 gene, and c.12064A>T(p.Lys4022Ter) and c.3321del(p.Gly1109GlufsTer13) in the FLG gene. Conclusion:This panel sequencing can provide effective genetic testing for neonates in NICU, especially in children with complex clinical diagnosis.