BackgroundThe Pediatric Quality of Life Inventory (PedsQL) is widely used instrument to measure pediatric health-related quality of life (HRQOL) for children aged 2 to 18 years. The purpose of the current study was to investigate the feasibility, reliability and validity of the Chinese mandarin version of the PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module in a group of Chinese children with cancer.MethodsThe PedsQL 4.0 Genetic Core Scales and the PedsQL 3.0 Cancer Module were administered to children with cancer (aged 5-18 years) and parents of such children (aged 2-18 years). For comparison, a survey on a demographically group-matched sample of the general population with children (aged 5-18) and parents of children (aged 2-18 years) was conducted with the PedsQL 4.0 Genetic Core Scales.ResultThe minimal mean percentage of missing item responses (except the School Functioning scale) supported the feasibility of the PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module for Chinese children with cancer. Most of the scales showed satisfactory reliability with Cronbach's α of exceeding 0.70, and all scales demonstrated sufficient test-retest reliability. Assessing the clinical validity of the questionnaires, statistically significant difference was found between healthy children and children with cancer, and between children on-treatment versus off-treatment ≥12 months. Positive significant correlations were observed between the scores of the PedsQL 4.0 Generic Core Scale and the PedsQL 3.0 Cancer Module. Exploratory factor analysis demonstrated sufficient factorial validity. Moderate to good agreement was found between child self- and parent proxy-reports.ConclusionThe findings support the feasibility, reliability and validity of the Chinese Mandarin version of PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module in children with cancer living in mainland China.

Accumulated evidence suggests a major role for the activation of the Sonic Hedgehog (SHH) signaling pathway in the development of neural crest stem cells that give rise to the sympathetic nervous system. We therefore investigated the involvement of SHH signaling in the pathogenesis of neuroblastoma, a common childhood malignant tumor of the sympathetic nervous system. Human neuroblastoma cell lines and a majority of primary neuroblastoma specimens showed high-level expression of the pathway targets and components, indicating persistent activation of the SHH pathway. All of the neuroblastoma cell lines we examined expressed significant levels of SHH ligand, suggesting an autocrine, ligand-dependent activation of the SHH pathway in neuroblastoma cells. S onic Hedgehog (SHH) is a member of the Hedgehog family of signaling proteins that were originally identified by their homology to the Drosophila melanogaster segment polarity gene Hedgehog. SHH induces signaling by binding to its receptor, Patched 1 (PTCH1), which inactivates PTCH1 and prevents it from inhibiting the transmembrane protein Smoothened (SMO). This signaling eventually results in the activation of GLI transcription factors, which, in turn, regulate the expression of many target genes that control cell growth, survival, and differentiation in a wide variety of tissues. Aberrant activation of the SHH signaling pathway has been implicated in the pathogenesis of various types of cancer.(1-3) Neuroblastoma (NB) is a childhood malignant tumor of neural crest origin, arising in the sympathetic nervous system.(4) Several lines of evidence suggest an important role for SHH signaling in regulating the development of neural crest stem cells and the sympathetic nervous system. First, inhibition of SHH signaling in vivo results in neural crest cell death.(5) Second, SHH promotes proliferation but inhibits neuronal differentiation of enteric neural crest stem cells.(6) Third, SHH signaling in neural crest stem cells is essential for the patterning and growth of facial primordia. Finally, SHH signaling promotes the proliferation of postnatal sympathetic cells in culture. (8) As aberrant activation of developmental pathways plays a key role in cancer pathogenesis, we investigated the significance of SHH signaling in NB cell growth and tumorigenesis. Materials and MethodsClinical specimens. Forty NB samples were obtained from

The findings provide support for the measurement properties of the Chinese version PedsQL 4.0 Generic Core Scales and 3.0 CP Module in pediatric CP.

Introduction: Cancer patients are prone to infections, but the mortality of fatal infections remains unclear. Understanding the patterns of fatal infections in patients with cancer is imperative. In this study, we report the characteristics, incidence, and predictive risk factors of fatal infections among a populationbased cancer cohort. Methods: A total of 8,471,051 patients diagnosed with cancer between 1975 and 2016 were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER) program. The primary outcome was dying from fatal infections. Mortality rates and standardized mortality ratios (SMRs) adjusted for age, sex, race, and calendar year were calculated to characterize the relative risks of dying from fatal infections and to compare with the general population. Furthermore, cumulative mortality rates and the Cox regression models were applied to identify predictive risk factors of fatal infections. Results: In cancer patients, the mortality rate of fatal infections was 260.1/100,000 personyears, nearly three times that of the general population [SMR, 2.92; 95% (confidence interval) CI 2.91-2.94]. Notably, a decreasing trend in mortality rate of fatal infections was observed in recent decades. SMRs of fatal infections were highest in Kaposi sarcoma (SMR, 162.2; 95% CI 159.4-165.1), liver cancer (SMR, 30.9; 95% CI 30.0-31.8), acute lymphocytic leukemia (SMR, 19.1; 95% CI 17.0-21.4), and acute myeloid leukemia (SMR, 13.3; 95% CI 12.4-14.3). Patients aged between 20 and 39 years old exhibited a higher cumulative mortality rate in the first few years after cancer diagnosis, whereas the cumulative mortality rate of those Yongqiang Zheng, Ying Chen and Kaixu Yu are co-first authors.

Simple SummaryHeat stress can induce oxidative stress and has an adverse effect on the growth and reproductive performance in animals. Curcumin, a plant-derived substance, with the effect of scavenging oxidative free radicals, improving immune response and anti-apoptosis, has been widely used as a dietary supplement in the livestock industry. The present study aims to investigate the effect of a curcumin dietary supplement on the blood metabolites, antioxidant status, immune response, and testicular gene expression in Hu Sheep in summer. The results show that dietary curcumin supplementation (450 and 900 mg/per sheep daily) can promote lipid metabolism, antioxidant capacity, and immune response as well as testicular development in Hu sheep, which provides evidence for the protective role of curcumin against heat stress in sheep.AbstractIn summer, the high temperature affects animal growth and reproductive performance. Curcumin is a flavonoid with anti-oxidant and anti-inflammatory effects. To evaluate the effects of dietary curcumin supplement on the blood biochemical parameters and testicular gene expressions in Hu sheep in summer, a total of 144 male Hu sheep aged four months were randomly divided into three groups (Con, Cur1, and Cur2, n = 48). Sheep in Con, Cur1, and Cur2 groups were fed a basal diet supplement with 0, 450, and 900 mg (per sheep) curcumin daily, respectively. Sheep were fed for 35 days, including a pre-feed for seven days. The results showed that the supplement with 450 mg and 900 mg curcumin increased serum free fatty acid (NEFA) and glutathione peroxidase (GPX), as well as IgA and IgM. The supplement with 450 mg curcumin increased the IgG level, while the supplement with 900 mg curcumin had a lower IgG level than the supplement with 450 mg curcumin (p < 0.05). Dietary curcumin supplement increased testicular organ index, serum testosterone level, and testicular star mRNA expression (p < 0.05). Furthermore, dietary curcumin supplement linearly inhibited testicular apoptosis with increased testicular bcl-2 mRNA expression and decreased caspase-3 mRNA expression (p < 0.05). In conclusion, dietary curcumin supplement can promote lipid metabolism, antioxidant capacity, and immune response, as well as testicular development, in Hu sheep, which provides evidence of application of curcumin in sheep production.

Objectives: Sonic hedgehog (Shh) signaling pathway is associated with tumor development; however, the role of Shh signaling in the development of olfactory neuroblastoma (ONB) is unknown. This study aimed to investigate the relationship between the regulation of Shh signaling and the pathogenesis of ONB. Methods: The expression of Shh signaling components was characterized by immunohistochemistry in human non-tumor olfactory epithelium and ONB specimens, and by RT-PCR and immunoblotting in human ONB cell lines. The impact of the treatment with cyclopamine (a selective inhibitor of the Shh pathway) and/or exogenous Shh on ONB cell proliferation, cycle and apoptosis was examined by MTT, soft agar colony formation and flow cytometry assays, respectively. The influence of Shh signaling on the expression of Shh signaling components and cell cycle-related regulators was determined by immunoblotting and quantitative RT-PCR, respectively. Results: The expression of Pacthed1, Gli1 and Gli2 was detected in 70, 70, and 65% of human ONB specimens, respectively, and in proportion of ONB cell lines, but not in non-tumor olfactory epithelium. Treatment with cyclopamine inhibited the proliferation and colony formation of ONB cells, induced ONB cell cycle arrest and apoptosis, and down-regulated the expression of Pacthed1, Gli1 and cyclin D1, but up-regulated p21 expression in vitro. These regulatory effects of cyclopamine were partially or completely erased by exogenous Shh. Conclusion: These data suggest that the Shh signaling pathway is crucial for the growth of ONB.

Purpose To identify disease-causing genes involved in female infertility. Methods Whole-exome sequencing and Sanger DNA sequencing were used to identify the mutations in disease-causing genes. We performed subcellular protein localization, western immunoblotting analysis, and co-immunoprecipitation analysis to evaluate the effects of the mutation. Results We investigated 17 families with female infertility. Whole-exome and Sanger DNA sequencing were used to characterize the disease gene in the patients, and we identified a novel heterozygous mutation (p.Ser173Cys, c.518C > G) in the ZP3 gene in a patient with empty follicle syndrome. When we performed co-immunoprecipitation analysis, we found that the S173C mutation affected interactions between ZP3 and ZP2. Conclusions We identified a novel mutation in the ZP3 gene in a Chinese family with female infertility. Our findings thus expand the mutational and phenotypical spectrum of the ZP3 gene, and they will be helpful in precisely diagnosing this aspect of female infertility.

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