RhoGEF Trio Regulates Radial Migration of Projection Neurons via Its Distinct Domains / 神经科学通报·英文版

The radial migration of cortical pyramidal neurons (PNs) during corticogenesis is necessary for establishing a multilayered cerebral cortex. Neuronal migration defects are considered a critical etiology of neurodevelopmental disorders, including autism spectrum disorders (ASDs), schizophrenia, epilepsy, and intellectual disability (ID). TRIO is a high-risk candidate gene for ASDs and ID. However, its role in embryonic radial migration and the etiology of ASDs and ID are not fully understood. In this study, we found that the in vivo conditional knockout or in utero knockout of Trio in excitatory precursors in the neocortex caused aberrant polarity and halted the migration of late-born PNs. Further investigation of the underlying mechanism revealed that the interaction of the Trio N-terminal SH3 domain with Myosin X mediated the adherence of migrating neurons to radial glial fibers through regulating the membrane location of neuronal cadherin (N-cadherin). Also, independent or synergistic overexpression of RAC1 and RHOA showed different phenotypic recoveries of the abnormal neuronal migration by affecting the morphological transition and/or the glial fiber-dependent locomotion. Taken together, our findings clarify a novel mechanism of Trio in regulating N-cadherin cell surface expression via the interaction of Myosin X with its N-terminal SH3 domain. These results suggest the vital roles of the guanine nucleotide exchange factor 1 (GEF1) and GEF2 domains in regulating radial migration by activating their Rho GTPase effectors in both distinct and cooperative manners, which might be associated with the abnormal phenotypes in neurodevelopmental disorders.

Clinical significance and cost-benefit analysis of serum calcitonin assay in diagnosis and treatment of medullary thyroid carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective@#To study the clinical significance of serum calcitonin in the diagnosis and treatment of medullary thyroid carcinoma and to analyze its cost-benefit.@*Methods@#One hundred and forty one patients with medullary thyroid carcinoma who undertook calcitonin test and frozen pathological examination were enrolled in this study from Oct 2012 to Mar 2018. Using the method of χ2 test, the positive rate of calcitonin test and frozen pathological examination in diagnosis of medullary thyroid carcinoma(MTC) were compared. Firstly, we compared the correct checkout cost of calcitonin test and that of frozen pathological examination (total number of patients×cost of examination/the correctly detected number of patients) . Secondly, we calculated whether calcitonin test help patients save money(average cost of treatment in hospital for MTC×number of patients who were evaluated to be candidate for surgery-cost of calcitonin test×total number of patients)/total number of patients.@*Results@#139 patients were positive in calcitonin test among 141 patients, and the positive rate was 98.58%. 91 patients were positive in frozen pathological examination, and the positive rate was 64.54% (χ2=97.821, P<0.000 1) . Cost-benefit analysis showed that the correct checkout cost of calcitonin test and frozen pathological examination were 71.01 yuan and 426.10 yuan, also,1 371 938.64 yuan could be saved totally and 9 730.06 yuan could be saved per patient because of calcitonin test.@*Conclusion@#Serum calcitonin test had a significant effect on the diagnosis and treatment of medullary thyroid carcinoma and was economical and practical.

The relationship between serum aggrecan catabolic fragments and joint Sharp assessment in patients with rheumatoid arthritis / 中华风湿病学杂志

Objective To investigate the relationship between abnormal metabolism of aggrecan and joint destruction in patients with rheumatoid arthritis (RA).Methods 140 RA patients with duration less than 24 months were enrolled into this study.The study also included 100 normal controls and 95 patients with other rheumatic diseases.Three monoclonal antibodies (5D4,7D4 and BC-3) of aggrecan were used to detected aggrecan catabolic fragments in serum of RA patients and the other two groups of controls by enzyme linked immunosorbent assay (ELISA),and the correlation of aggrecan catabolic fragments with joint damage were analyzed.Sharp evaluation of hand joints in RA patients were performed at baseline and after one year follow-up.Calculating the area under the receiver operating characteristic curve (ROC) was used to evaluate the sensitivity and specificity of aggrecan catabolic fragments detected in serum of RA patients.Results Both levels of 5D4 fragment and BC-3 fragment of RA group were higher than those of normal control [5D4 of RA:(5.8±2.1) ng/μl,normal control:(2.2±1.3) ng/μl;BC-3 of RA:(11.1±3.4) ng/μl,normal control:(5.0±2.1) ng/μl,F=38.65,24.07,P＜0.001).There was no difference in 7D4 fragment among three groups (F=0.589,P=0.478).Both two fragment levels of RA patients with anti-CCP positive were greater than those patients with anti-CCP negative [5D4:(5.6±1.3) ng/μl vs (4.4±1.1) ng/μl,F=21.23,P＜0.01;BC-3:(12.2±3.9) ng/μl vs (9.3±2.8) ng/μ1,F=27.14,P＜0.01].Linear Regression showed that serum fragments detected by 5D4 and BC-3,and anti-CCP positive were risk factors for Sharp deterioration after one year follow-up.The sensitivity and specificity of combined detection of two aggrecan fragments in serum of RA patients for the prediction of joint Sharp were 56.5％ and 84.2％ respectively.Positive predictive value and negative predictive value are 74.3％ and 70.6％.respectively.Application of areas of ROC to identify the best evaluation of Sharp was 0.798.Conclusion There is positive correlation between aggrecan catabolic fragments in serum and joint Sharp evaluation of RA patients.Detection of aggrecan catabolic fragments in RA patients may predict early joint destruction.