Yuchan Li

Effect of Variation of ABCB1 and ABCC3 Genotypes on the Survival of Bone Tumor Cases after Chemotherapy

We conducted a comprehensive study to investigate the role of genes involved in transport pathways in response to chemotherapy and clinical outcome of osteosarcoma cases. Genotyping of six SNPs was performed in a 384-well plate format on the Sequenom MassARRAY platform for 208 osteosarcoma patients to reveal any correlations of the six SNPs with response to chemotherapy and clinical outcome. Individuals with the ABCB1 rs1128503 TT and ABCC3 rs4148416 TT genotypes had a higher probability of responding poorly to chemotherapy, indicated by odds ratios (ORs) of 2.46 (95%CI, 1.21-5.74) and 3.78 (95% CI, 1.20-13.85), respectively. Moreover, the ABCB1 rs1128503 TT and ABCC3 rs4148416 TT genotypes were significantly associated with shorter disease- free survival (DFS) and overall survival (OS). Our study found the two SNPs in two transporter genes and one phase II metabolism enzyme to be associated with response to chemotherapy and overall survival in osteosarcoma patients, suggesting potential prognostic biomarker applications of the two SNPs.

Novel frame-shift mutations of GLI3 gene in non-syndromic postaxial polydactyly patients

Polydactyly is a common congenital limb deformity. This anomaly may occur in isolation (non-syndromic) or as part of a syndrome. The glioma-associated oncogene family zinc finger 3 (GLI3) is known to be associated with both syndromic and non-syndromic polydactyly. GLI3 plays a predominant role in the pathogenesis of syndromic polydactyly: mutations have been identified in 68% of patients with Greig cephalopolysyndactyly syndrome and 91% of patients with Pallister-Hall syndrome. The knowledge regarding the contribution of GLI3 in non-syndromic polydactyly is currently very limited. In this study, we assembled a cohort of individuals of Chinese ethnicity with non-syndromic postaxial polydactyly. We presented the clinical features and molecular evaluations of 19 probands. GLI3 mutations were identified in 15.8% of probands (3/19) including two novel frame-shift mutations c.3855dupC (p.Met1286HisfsTer18) and c.4141delA (p.Arg1381GlyfsTer38) detected in sporadic cases and one previously reported nonsense mutation (c.1927C>T/p.Arg643Ter) in a familial case. Of note, GLI3 mutations were exclusively detected in patients with bilateral polydactyly affecting both hands and feet. Three out of five (60%) probands with bilateral polydactyly on both hands and feet carried pathogenic mutations in GLI3. Our study demonstrated the role of GLI3 in a significant fraction of patients with non-syndromic bilateral polydactyly affecting both hands and feet.

A New Subtype of Multiple‐Synostoses Syndrome is Caused by a Mutation in GDF6 that Decreases its Sensitivity to Noggin and Enhances its Potency as a BMP Signal

Growth and differentiation factors (GDFs) are secreted signaling molecules within the BMP family that have critical roles in joint morphogenesis during skeletal development in mice and humans. Using genetic data obtained from a six‐generation Chinese family, we identified a missense variant in GDF6 (NP_001001557.1; p.Y444N) that fully segregates with a novel autosomal dominant synostoses (SYNS) phenotype, which we designate as SYNS4. Affected individuals display bilateral wrist and ankle deformities at birth and progressive conductive deafness after age 40 years. We find that the Y444N variant affects a highly conserved residue of GDF6 in a region critical for binding of GDF6 to its receptor(s) and to the BMP antagonist NOG, and show that this mutant GDF6 is a more potent stimulator of the canonical BMP signaling pathway compared with wild‐type GDF6. Further, we determine that the enhanced BMP activity exhibited by mutant GDF6 is attributable to resistance to NOG‐mediated antagonism. Collectively, our findings indicate that increased BMP signaling owing to a GDF6 gain‐of‐function mutation is responsible for loss of joint formation and profound functional impairment in patients with SYNS4. More broadly, our study highlights the delicate balance of BMP signaling required for proper joint morphogenesis and reinforces the critical role of BMP signaling in skeletal development.

Identification of Four Novel EXT1 and EXT2 Mutations in Five Chinese Pedigrees with Hereditary Multiple Exostoses

Hereditary multiple exostoses (HME) is an autosomal dominant skeletal disorder most frequently caused by the EXT1 and EXT2 gene mutations resulting in reduction or absence of heparan sulfate (HS) in the exostotic cartilage cap. In this study, we investigated the molecular defects in five Chinese pedigrees with HME by direct sequencing analysis. Two novel EXT1 gene mutations and two novel EXT2 gene mutations were identified in two and three pedigrees, respectively. Of the four mutations identified, the c.651-664delinsTTT and c.680delG mutations in the exon 1 of EXT1 gene would cause frameshift (K218fs and R227fs) and introduce premature stop codon at amino acid site 220 and 251, respectively. The two missense mutations of c.398T > G in exon 2 and c.1016G > A in exon 6 of EXT2 gene result in the Leu133Arg and Cys339Tyr substitution, respectively. As HME is caused by defects in HS synthesis that is a complex process and not fully understood, these naturally occurring EXT mutations may provide important clues to future studies elucidating how EXT proteins contribute to HS biosynthesis.

Pre-bent elastic stable intramedullary nail fixation for distal radial shaft fractures in children

Objective:  To investigate the functional and radiographic outcomes of pre‐bent elastic stable intramedullary nail in treatment of distal radial shaft fractures in children.

Risk factors for refracture of the forearm in children treated with elastic stable intramedullary nailing

PurposeThis study aims to investigate risk factors for refracture of the forearm in children treated with elastic stable intramedullary nailing (ESIN).MethodsClinical data of 267 patients who had been treated for forearm fractures by ESIN in our hospital from January 2010 to December 2014 were retrospectively reviewed. Risk factors for forearm refractures were determined using logistic regression analysis.ResultsForearm refractures occurred in 11 children. Univariate analysis revealed that age, body weight, number of fractures, open fracture, nail diameter, and immobilization time were not associated with refractures. However, gender (male, P = 0.042) and fracture location (lower third, P = 0.007) were significantly associated with refractures. Multivariate analysis revealed that fracture location was an independent risk factor for forearm refractures (P = 0.031).ConclusionForearm refracture is uncommon in children treated with ESIN. Fracture location is an independent risk factor for forearm refractures in these patients.

Effects of inclusion on the creep rate of piezoelectric films

ABSTRACT This paper presents an analytical method to study the effect of inclusions in piezoelectric materials on the creep rate. The driven force for the creep rate of piezoelectric materials with inclusion is from diffusional mass transport along the inclusion interface. The results show that the creep rate of piezoelectric materials containing the rigid inclusion with the shape parameter m = 0.8 appears at the minimum, and the effect of inclusion volume fraction on the creep rate of piezoelectric materials with soft inclusion becomes the smaller and smaller, as the stiffness of soft inclusion decreases. Thus, the effect of inclusion on creep characteristics can be improved by controlling the material property, the sizes, shapes, and volume ratio of inclusions.

A novel EXT1 gene mutation causing hereditary multiple exostoses in a Chinese pedigree

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