OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with Hereditary spastic paraplegia type 3A (SPG3A) and the genotype-phenotype correlation. METHODS: A three-generation pedigree presented at Huantai Maternal and Child Health Care Hospital in March 2021 was selected as the study subject. Whole-exome sequencing (WES) and pedigree analysis was carried out. Candidate variant was validated by Sanger sequencing of the members from the pedigree. Haplotype analysis was used to trace the origin of the variant, and pathogenicity was rated based on the 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.: 2025-12). RESULTS: A c.1024C>T (p.Pro342Ser) variant of the ATL1 was identified in the four affected members, including the proband, but none of the three unaffected relatives. Haplotype analysis suggested that the variant was derived from the proband's mother and has co-segregated with the disease phenotype. Based on the guidelines of the ACMG, it was classified as likely pathogenic. CONCLUSION The ATL1 c.1024C>T (p.Pro342Ser) variant probably underlay the pathogenesis in this pedigree. Above finding has enriched the mutational spectrum of ATL1 and phenotypic spectrum of SPG3A in the Chinese population, and enabled genetic counseling for this pedigree.
Humans ; Pedigree ; Spastic Paraplegia, Hereditary/genetics* ; Male ; Female ; Asian People/genetics* ; Adult ; Haplotypes ; Membrane Proteins/genetics* ; Exome Sequencing ; GTP-Binding Proteins/genetics* ; Mutation ; Middle Aged ; China ; Genetic Association Studies ; East Asian People

BACKGROUND:When performing percutaneous minimally invasive transforaminal lumbar interbody fusion to implant an intervertebral cage,due to the narrow operating range of the approach,there is a risk of nerve root injury or poor position of cage. To solve the above problems,a novel mechanical deformable press-fit cage (YP-cage) was invented.OBJECTIVE:To preliminarily evaluate the mechanical strength characteristics of this new lumbar fusion device YP-cage.METHODS:Static axial compression and torsion tests were conducted on 9,11,and 13 mm YP-cages (n=9) and poly (ether ether ketone) (PEEK)-cages (n=9). The force-displacement curves were collected to calculate yield displacement and load,ultimate load displacement and stiffness,yield angular displacement and torque,ultimate load and angle displacement torque and stiffness for comparative analysis. RESULTS AND CONCLUSION:(1) In the static axial compression test,YP-cage was superior to PEEK-cage in terms of stiffness,yield load,ultimate displacement,and load limit in three groups of tests (9,11,13 mm) (P<0.01),but the yield displacement of YP-cage was smaller than that of PEEK-cage (P<0.05). (2) In the static torsion test,there was no significant difference in the ultimate torsion angle between YP-cage and PEEK-cage in 9 mm group. YP-cage was lower thanPEEK-cage in yield torque,yield torsion angle,and ultimate torque (P<0.01),while YP-cage torsional stiffness was greater than PEEK-cage in 9 mm group and 11 mm group (P<0.01). (3) The results show that the novel press-fit mechanical lumbar cage has higher compressive strength than PEEK cage,but the torsional strength is not as good as PEEK-cage.

Objective:To assess the value of whole exome sequencing (WES) for the diagnosis of early-onset genetic diseases among infants aged 0 to 6 month in Ningbo region.Methods:268 infants presented at the Women and Children′s Hospital Affiliated to Ningbo University from January 2022 to June 2024 undergoing WES-based genetic testing were enrolled. Peripheral blood samples were collected from the infants and their parents and subjected to WES. Pathogenic variants were identified by clinical manifestations. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. EC2023-017).Results:Among the 268 infants, 124 (46.3%) had phenotype-explaining genetic variants. For 42 family-based WES tests, 20 (47.62%) were abnormal, whilst in 226 single-person WES tests, 104 (46.02%) had abnormalities, with 76 (33.63%) verified by parental testing. In 96 fully family-verified cases, 31 were de novo, 40 were parent-inherited, 25 were single-parent-inherited. These included 35 inborn metabolic errors, 28 rare syndromes, 9 neurodevelopmental disorders, 4 musculoskeletal diseases, 5 congenital deafness, 2 mitochondrial diseases, 4 endocrine diseases, and 9 others. Among these, there were 7 pathogenic copy number variations (all deletions), 3 chromosomal abnormalities, and 85 single-nucleotide variations. One case of Beckwith-Wiedemann syndrome was detected by methylation MLPA. Among the single-nucleotide variants, 114 pathogenic/likely pathogenic variants were identified in 61 genes, with common ones including missense variants (64.04%), frameshifting variants (20.18%) and splicing variants (4.39%). Conclusion:WES can offer effective diagnosis for hereditary diseases with specific/non-specific manifestations. For early-age infants, higher detection rates may be attained for inborn metabolic errors, rare syndromes, neurodevelopmental disorders, congenital deafness, and musculoskeletal diseases. Compared with single-person WES, family-based WES can attain a higher diagnostic efficiency.

OBJECTIVE: To assess the value of whole exome sequencing (WES) for the diagnosis of early-onset genetic diseases among infants aged 0 to 6 month in Ningbo region. METHODS: 268 infants presented at the Women and Children's Hospital Affiliated to Ningbo University from January 2022 to June 2024 undergoing WES-based genetic testing were enrolled. Peripheral blood samples were collected from the infants and their parents and subjected to WES. Pathogenic variants were identified by clinical manifestations. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. EC2023-017). RESULTS: Among the 268 infants, 124 (46.3%) had phenotype-explaining genetic variants. For 42 family-based WES tests, 20 (47.62%) were abnormal, whilst in 226 single-person WES tests, 104 (46.02%) had abnormalities, with 76 (33.63%) verified by parental testing. In 96 fully family-verified cases, 31 were de novo, 40 were parent-inherited, 25 were single-parent-inherited. These included 35 inborn metabolic errors, 28 rare syndromes, 9 neurodevelopmental disorders, 4 musculoskeletal diseases, 5 congenital deafness, 2 mitochondrial diseases, 4 endocrine diseases, and 9 others. Among these, there were 7 pathogenic copy number variations (all deletions), 3 chromosomal abnormalities, and 85 single-nucleotide variations. One case of Beckwith-Wiedemann syndrome was detected by methylation MLPA. Among the single-nucleotide variants, 114 pathogenic/likely pathogenic variants were identified in 61 genes, with common ones including missense variants (64.04%), frameshifting variants (20.18%) and splicing variants (4.39%). CONCLUSION WES can offer effective diagnosis for hereditary diseases with specific/non-specific manifestations. For early-age infants, higher detection rates may be attained for inborn metabolic errors, rare syndromes, neurodevelopmental disorders, congenital deafness, and musculoskeletal diseases. Compared with single-person WES, family-based WES can attain a higher diagnostic efficiency.
Humans ; Exome Sequencing/methods* ; Infant ; Female ; Male ; Infant, Newborn ; Genetic Diseases, Inborn/diagnosis* ; Genetic Testing/methods*

BACKGROUND:When performing percutaneous minimally invasive transforaminal lumbar interbody fusion to implant an intervertebral cage,due to the narrow operating range of the approach,there is a risk of nerve root injury or poor position of cage. To solve the above problems,a novel mechanical deformable press-fit cage (YP-cage) was invented.OBJECTIVE:To preliminarily evaluate the mechanical strength characteristics of this new lumbar fusion device YP-cage.METHODS:Static axial compression and torsion tests were conducted on 9,11,and 13 mm YP-cages (n=9) and poly (ether ether ketone) (PEEK)-cages (n=9). The force-displacement curves were collected to calculate yield displacement and load,ultimate load displacement and stiffness,yield angular displacement and torque,ultimate load and angle displacement torque and stiffness for comparative analysis. RESULTS AND CONCLUSION:(1) In the static axial compression test,YP-cage was superior to PEEK-cage in terms of stiffness,yield load,ultimate displacement,and load limit in three groups of tests (9,11,13 mm) (P<0.01),but the yield displacement of YP-cage was smaller than that of PEEK-cage (P<0.05). (2) In the static torsion test,there was no significant difference in the ultimate torsion angle between YP-cage and PEEK-cage in 9 mm group. YP-cage was lower thanPEEK-cage in yield torque,yield torsion angle,and ultimate torque (P<0.01),while YP-cage torsional stiffness was greater than PEEK-cage in 9 mm group and 11 mm group (P<0.01). (3) The results show that the novel press-fit mechanical lumbar cage has higher compressive strength than PEEK cage,but the torsional strength is not as good as PEEK-cage.

Objective:To assess the value of whole exome sequencing (WES) for the diagnosis of early-onset genetic diseases among infants aged 0 to 6 month in Ningbo region.Methods:268 infants presented at the Women and Children′s Hospital Affiliated to Ningbo University from January 2022 to June 2024 undergoing WES-based genetic testing were enrolled. Peripheral blood samples were collected from the infants and their parents and subjected to WES. Pathogenic variants were identified by clinical manifestations. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. EC2023-017).Results:Among the 268 infants, 124 (46.3%) had phenotype-explaining genetic variants. For 42 family-based WES tests, 20 (47.62%) were abnormal, whilst in 226 single-person WES tests, 104 (46.02%) had abnormalities, with 76 (33.63%) verified by parental testing. In 96 fully family-verified cases, 31 were de novo, 40 were parent-inherited, 25 were single-parent-inherited. These included 35 inborn metabolic errors, 28 rare syndromes, 9 neurodevelopmental disorders, 4 musculoskeletal diseases, 5 congenital deafness, 2 mitochondrial diseases, 4 endocrine diseases, and 9 others. Among these, there were 7 pathogenic copy number variations (all deletions), 3 chromosomal abnormalities, and 85 single-nucleotide variations. One case of Beckwith-Wiedemann syndrome was detected by methylation MLPA. Among the single-nucleotide variants, 114 pathogenic/likely pathogenic variants were identified in 61 genes, with common ones including missense variants (64.04%), frameshifting variants (20.18%) and splicing variants (4.39%). Conclusion:WES can offer effective diagnosis for hereditary diseases with specific/non-specific manifestations. For early-age infants, higher detection rates may be attained for inborn metabolic errors, rare syndromes, neurodevelopmental disorders, congenital deafness, and musculoskeletal diseases. Compared with single-person WES, family-based WES can attain a higher diagnostic efficiency.

Objective To investigate the correlation between Young′s elastic modulus (EI) using shear wave elastography (SWE) and liver pathology .Methods Liver biopsy was performed on 231 patients with chronic hepatitis B (CHB) under supersonic guidance ,and SWE with EI of liver was obtained concurrently .The correlation between measured liver stiffness and pathology was analyzed by using the liver pathology as golden standards .One‐way analysis of variance and Spearman rank correlation analysis were performed for the comparison between groups and correlation between two variables , respectively .Receiver operating characteristic (ROC) curve was used to explore the predictive value of shear modulus for the liver inflammation grades and fibrosis stages .Results The EI medians of different liver inflammation grades were 6 .78 kPa (G1) ,7 .30 kPa (G2) ,9 .93 kPa (G3) and 14 .93 kPa (G4) , respectively ,which were statistically different (H=55 .19 ,P<0 .01) .And EI medians of various fibrosis stages were 6 .62 kPa (S0 -S1) ,7 .15 kPa (S2) ,9 .78 kPa (S3) and 14 .62 kPa (S4) ,respectively , which were also significantly different (H=62 .14 ,P<0 .01) .EI was positively correlated with both liver inflammation grades (r=0 .454 6 ,P<0 .01) and liver fibrosis stages (r=0 .505 6 ,P<0 .01) .The areas under the ROC for G≥2 ,G≥3 and G=4 were 0 .68 (95% CI:0 .61 -0 .75) ,0 .77 (95% CI:0 .70 -0 .84) and 0 .85 (95% CI:0 .77-0 .92) ,respectively .The areas under the ROC for S≥2 ,S≥3 and S=4 w ere 0 .73 (95% C I:0 .66 -0 .79 ) ,0 .78 (95% C I:0 .72 -0 .85 ) and 0 .83 (95% C I:0 .75 -0 .91 ) , respectively .Conclusion The EI measured by SWE is correlated with liver pathology of CHB patients , which may be used to dynamically monitor the progress of liver fibrosis .

Biopsy ; Endopeptidase K ; Fluorescent Antibody Technique ; Glomerulonephritis, IGA ; pathology ; Glomerulonephritis, Membranous ; pathology ; Humans ; Kidney ; pathology ; Lupus Nephritis ; pathology ; Paraffin Embedding ; Staining and Labeling

Objective To verify the convergent validity,discriminant validity and concurrent validity of the Action Research Arm Test(ARAT)in patients with chronic stroke.Methods 30 cases with chronic stroke were assessed with ARAT,upper limb section at Fugl-Meyer Assessment and Motor Activity Log(MAL)on the same day.The validity was investigated using Spearman ρ and t test.Results The scores of the ARAT closely correlated with upper limb section at Fugl-Meyer Assessment(ρ=0.906,P<0.001).The upper limb section at Fugl-Meyer scores≥33 group achieved a significantly higher scores of the ARAT than the scores<33 group(t =6.614,P<0.001).The scores of the ARAT closely correlated with the amount of use(AOU)and quality of movement(QOM)of MAL(ρ=0.894 and 0.761,respectively,P<0.001).Conclusion The ARAT has been shown good convergent validity,discriminant validity and concurrent validity in people with stroke.

Objective To verify the inter-rater reliability,intra-rater reliability and internal reliability of the action research arm test(ARAT)in patients with chronic stroke.Methods 30 people with chronic stroke were tested with the ARAT by two experienced raters.The inter-rater reliability,intra-rater reliability and internal reliability were examined.Results The ARAT showed high inter-rater reliability and intra-rater reliability(ICC=0.992 and 0.987,respectively)and internal consistency(Cronbach's alpha coefficient=0.936).Conclusion The ARAT shows good inter-rater reliability,intra-rater reliability and internal reliability in assessing patients after stroke.