Development and Application of Comprehensive Evaluation System in the Treatment of Children with Hemophilia in China

Being a hereditary bleeding disorder, hemophilia is characterized by spontaneous bleeding, especially joint bleeding. The treatment outcome is a comprehensive evaluation system of the following three aspects: bleeding, musculoskeletal structure (imaging), and function-activity participation. Multidisciplinary testing and corresponding scales are needed in the assessment. Among them, the quality of life assessment of hemophilia patients is particularly important, through general questionnaires and hemophilia-specific questionnaires. Canadian hemophilia outcomes-Kids' life assessment tool(CHO-KLAT), a special quality of life assessment tool for children with hemophilia, is the most widely used. This paper briefly describes the development and application of comprehensive evaluation system of the children with the disease

Altered structural-functional coupling of large-scale brain networks in early Tourette syndrome children

Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder and its pathophysiological mechanism remains elusive. At present, TS-related abnormalities in either structural connectivity (SC) or functional connectivity (FC) have extensively been described, and discrepancies were apparent between the SC and FC studies. However, abnormalities in the SC-FC correlation for early TS children remain poorly understood. In our study, we used probabilistic diffusion tractography and resting-state FC to construct large-scale structural and functional brain networks for 34 drug-naive TS children and 42 healthy children. Graph theoretical approaches were employed to divide the group-averaged FC networks into functional modules. The Pearson correlation between the entries of SC and FC were estimated as SC-FC coupling within whole-brain and each module. Although five common functional modules (including the sensorimotor, default-mode, fronto-parietal, temporo-occipital and subcortical modules) were identified in both groups, we found SC-FC coupling in TS exhibited increased at the whole-brain and functional modular level, especially within sensorimotor and subcortical modules. The increased SC-FC coupling may suggest that TS pathology leads to functional interactions that are more directly related to the underlying SC of the brain and may be indicative of more stringent and less dynamic brain function in TS children. Together, our study demonstrated that altered whole-brain and module-dependent SC-FC couplings may underlie abnormal brain function in TS, and highlighted the potential for using multimodal neuroimaging biomarkers for TS diagnosis as well as understanding the pathophysiologic mechanisms of TS. &copy; 2018 SPIE.</p

The Evidence for Association of <i>ATP2B2</i> Polymorphisms with Autism in Chinese Han Population

<div><p>Background</p><p>Autism is a neurodevelopmental disorder with a high estimated heritability. <i>ATP2B2</i>, located on human chromosome 3p25.3, encodes the plasma membrane calcium-transporting ATPase 2 which extrudes Ca²⁺ from cytosol into extracellular space. Recent studies reported association between <i>ATP2B2</i> and autism in samples from Autism Genetic Resource Exchange (AGRE) and Italy. In this study, we investigated whether <i>ATP2B2</i> polymorphisms were associated with autism in Chinese Han population.</p><p>Methods</p><p>We performed a family based association study between five SNPs (rs35678 in exon, rs241509, rs3774180, rs3774179, and rs2278556 in introns) in <i>ATP2B2</i> and autism in 427 autism trios of Han Chinese descent. All SNPs were genotyped using the Sequenom genotyping platform. The family-based association test (FBAT) program was used to perform association test for SNPs and haplotype analyses.</p><p>Results</p><p>This study demonstrated a preferential transmission of T allele of rs3774179 to affected offsprings under an additive model (T>C, Z = 2.482, <i>p</i> = 0.013). While C allele of rs3774179 showed an undertransmission from parents to affected children under an additive and a dominant model, respectively (Z = −2.482, <i>p</i> = 0.013; Z = −2.591, <i>p</i> = 0.0096). Haplotype analyses revealed that three haplotypes were significantly associated with autism. The haplotype C-C (rs3774180–rs3774179) showed a significant undertransmission from parents to affected offsprings both in specific and global haplotype FBAT (Z = −2.037, <i>p</i> = 0.042; Global <i>p</i> = 0.03). As for the haplotype constructed by rs3774179 and rs2278556, C-A might be a protective haplotype (Z = −2.206, <i>p</i> = 0.027; Global <i>p</i> = 0.04), while T-A demonstrated an excess transmission from parents to affected offsprings (Z = 2.143, <i>p</i> = 0.032). These results were still significant after using the permutation method to obtain empirical <i>p</i> values.</p><p>Conclusions</p><p>Our research suggested that <i>ATP2B2</i> might play a role in the etiology of autism in Chinese Han population.</p></div

Cross-cultural adaptation of the CHO-KLAT for boys with hemophilia in rural and urban china

<p>Abstract</p> <p>Background</p> <p>Quality of life (QoL) is increasingly recognized as an important outcome measure in clinical trials. The Canadian Hemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT) shows promise for use in China.</p> <p>Objective</p> <p>To adapt the CHO-KLAT version 2.0 for use in clinical trials in China.</p> <p>Methods</p> <p>Forward and back translations of the CHO-KLAT_2.0 were completed in 2008. Between October 2009 and June 2010, a series of 3 focus groups were held with 20 boys and 31 parents in rural and urban China to elicit additional concepts, important to their QoL, for the Chinese CHO-KLAT_2.0. All of the items identified by boys and parents were reviewed by a group of experts, resulting in a Chinese version of the CHO-KLAT_2.0. This version underwent a detailed cognitive debriefing process between October 2010 and June 2011. Thirteen patient-parent pairs participated in this cognitive debriefing process until a stable and clearly understood Chinese version of the CHO-KLAT_2.0 was obtained.</p> <p>Results</p> <p>The initial back translation of the Chinese CHO-KLAT_2.0 was slightly discrepant from the original English version on 12 items. These were all successfully adjudicated. The focus groups identified 9 new items that formed an add-on Socio-Economic Context (SEC) module for China. Linguistic improvements were made after the 2^nd, 5^th, 7^th and 13^th cognitive debriefings pairs and affected a total of 18 items. The result was a 35 item CHO-KLAT_2.0 and a SEC module in Simplified Chinese, both of which have good content validity.</p> <p>Conclusion</p> <p>This detailed process proved to be extremely valuable in ensuring the items were accurately interpreted by Chinese boys with hemophilia ages ≤18 years. The need for the additional SEC module highlighted the different context that currently exists in China with regard to hemophilia care as compared to many Western countries, and will be important in tracking progress within both rural and urban China over time. Changes based on the cognitive debriefings suggest that expert verbatim translation alone is not sufficient. The Chinese version of the CHO-KLAT_2.0 is well understood by boys with hemophilia in China. Next steps will be to test its construct validity and reliability in boys with hemophilia in China.</p

Results of association between 5 SNPs in <i>ATP2B2</i> and autism and haplotype analyses in 427 trios of Han Chinese descent.

<p>Afreq, allele frequency; Families, number of informative families; S, test statistics for the observed number of transmitted alleles; E(S), expected value of S under the null hypothesis (i.e., no linkage and no association).</p>a<p>The number of permutationS is 10,000;</p>b<p>whole marker permutation test using minimal <i>p</i> (when only one haplotype was significant).</p

The information of SNPs in <i>ATP2B2</i> and primers of PCR and unextended primers for Sequenom SNP genotyping.

<p>SNP, single nucleotide polymorphism; PCR, polymerase chain reaction; UEP, unextended primer.</p