Plasma irisin associations with executive function among children in a prospective cohort.

OBJECTIVE: To examine the longitudinal associations between irisin and executive function among children, as well as the sex difference in this correlation. METHODS: The study involving 330 children aged 6-10 years conducted in Guangzhou, China. Baseline surveys and fasting blood samples were collected in 2017. Plasma irisin concentration was measured using Enzyme-Linked Immunosorbent Assay (ELISA). Executive function was assessed by the Behavior Rating Inventory of Executive Function (BRIEF) scale in 2017 and followed up after 2 years. Multivariable linear regression was used for association analysis. RESULTS: The plasma irisin concentration was 9.04±2.18 ng/mL. There was no statistical difference in plasma irisin and change values of BRIEF T-scores between boys and girls. No significant associations were found between plasma irisin and change values of BRIEF T-scores (P > 0.05) in the overall sample. Further subgroup analyses according to sex revealed that plasma irisin was negatively associated with change values of behavior regulation index (BRI, ß=-0.521, 95 %CI: -1.036 ∼ -0.006), emotional control (ß=-0.649, 95 %CI: -1.249 ∼ -0.049), working memory T-scores (ß=-0.774, 95 %CI: -1.350 ∼ -0.199) in girls. Moreover, we firstly identified a sex effect modification in the association of plasma irisin with change values of working memory T-score (Pinterference=0.012). CONCLUSIONS: Higher irisin concentration was associated with better executive function performance in girls. Further studies that included populations in other regions or countries are needed to confirm these findings.

Impaired effective functional connectivity in the social preference of children with autism spectrum disorder.

Background: The medial prefrontal cortex (mPFC), amygdala (Amyg), and nucleus accumbens (NAc) have been identified as critical players in the social preference of individuals with ASD. However, the specific pathophysiological mechanisms underlying this role requires further clarification. In the current study, we applied Granger Causality Analysis (GCA) to investigate the neural connectivity of these three brain regions of interest (ROIs) in patients with ASD, aiming to elucidate their associations with clinical features of the disorder. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from the ABIDE II database, which included 37 patients with ASD and 50 typically developing (TD) controls. The mPFC, Amyg, and NAc were defined as ROIs, and the differences in fractional amplitude of low-frequency fluctuations (fALFF) within the ROIs between the ASD and TD groups were computed. Subsequently, we employed GCA to investigate the bidirectional effective connectivity between the ROIs and the rest of the brain. Finally, we explored whether this effective connectivity was associated with the social responsiveness scale (SRS) scores of children with ASD. Results: The fALFF values in the ROIs were reduced in children with ASD when compared to the TD group. In terms of the efferent connectivity from the ROIs to the whole brain, the ASD group exhibited increased connectivity in the right cingulate gyrus and decreased connectivity in the right superior temporal gyrus. Regarding the afferent connectivity from the whole brain to the ROIs, the ASD group displayed increased connectivity in the right globus pallidus and decreased connectivity in the right cerebellar Crus 1 area and left cingulate gyrus. Additionally, we demonstrated a positive correlation between effective connectivity derived from GCA and SRS scores. Conclusion: Impairments in social preference ASD children is linked to impaired effective connectivity in brain regions associated with social cognition, emotional responses, social rewards, and social decision-making. This finding further reveals the potential neuropathological mechanisms underlying ASD.

The Associations of Prenatal Exposure to Fine Particulate Matter and Its Chemical Components with Allergic Rhinitis in Children and the Modification Effect of Polyunsaturated Fatty Acids: A Birth Cohort Study.

BACKGROUND: Polyunsaturated fatty acids (PUFAs) have been shown to protect against fine particulate matter <2.5µm in aerodynamic diameter (PM2.5)-induced hazards. However, limited evidence is available for respiratory health, particularly in pregnant women and their offspring. OBJECTIVES: We aimed to investigate the association of prenatal exposure to PM2.5 and its chemical components with allergic rhinitis (AR) in children and explore effect modification by maternal erythrocyte PUFAs. METHODS: This prospective birth cohort study involved 657 mother-child pairs from Guangzhou, China. Prenatal exposure to residential PM2.5 mass and its components [black carbon (BC), organic matter (OM), sulfate (SO42-), nitrate (NO3-), and ammonium (NH4+)] were estimated by an established spatiotemporal model. Maternal erythrocyte PUFAs during pregnancy were measured using gas chromatography. The diagnosis of AR and report of AR symptoms in children were assessed up to 2 years of age. We used Cox regression with the quantile-based g-computation approach to assess the individual and joint effects of PM2.5 components and examine the modification effects of maternal PUFA levels. RESULTS: Approximately 5.33% and 8.07% of children had AR and related symptoms, respectively. The average concentration of prenatal PM2.5 was 35.50±5.31 µg/m3. PM2.5 was positively associated with the risk of developing AR [hazard ratio (HR)=1.85; 95% confidence interval (CI): 1.16, 2.96 per 5 µg/m3] and its symptoms (HR=1.79; 95% CI: 1.22, 2.62 per 5 µg/m3) after adjustment for confounders. Similar associations were observed between individual PM2.5 components and AR outcomes. Each quintile change in a mixture of components was associated with an adjusted HR of 3.73 (95% CI: 1.80, 7.73) and 2.69 (95% CI: 1.55, 4.67) for AR and AR symptoms, with BC accounting for the largest contribution. Higher levels of n-3 docosapentaenoic acid and lower levels of n-6 linoleic acid showed alleviating effects on AR symptoms risk associated with exposure to PM2.5 and its components. CONCLUSION: Prenatal exposure to PM2.5 and its chemical components, particularly BC, was associated with AR/symptoms in early childhood. We highlight that PUFA biomarkers could modify the adverse effects of PM2.5 on respiratory allergy. https://doi.org/10.1289/EHP13524.

Examining associations of folic acid supplements administered to mothers during pre-conceptional and prenatal periods with autism spectrum disorders in their offspring: insights from a multi-center study in China.

Objective: To investigate the relationship between maternal folic acid (FA) supplementation during the pre-conceptional and prenatal periods and the subsequent risk of autism spectrum disorder (ASD) in offspring. Methods: A total of 6,049 toddlers aged 16-30 months were recruited from August 2016 to March 2017 for this cross-sectional study conducted in China. The parents of the enrolled toddlers provided information on maternal supplemental FA, socio-demographic information, and related covariates. Standard diagnostic procedures were implemented to identify toddlers with ASD. Results: Among the 6,049 children included in the study, consisting of 3,364 boys with an average age of 22.7 ± 4.1 months, a total of 71 children (1.2%) were diagnosed with ASD. Mothers who did not consume FA supplements during the prenatal period were found to have a significantly increased risk of having offspring with ASD, in comparison to those who were exposed to FA supplements (odds ratio [OR] = 2.47). However, we did not find a similar association during the pre-conceptional period. Compared to mothers who consistently used FA supplements from pre-conception to the prenatal period, those who never used FA supplements were statistically significantly associated with a higher risk of ASD in their offspring (OR = 2.88). Conclusion: This study indicated that providing continuous maternal FA supplementation during the pre-conceptional and prenatal periods may decrease the risk of ASD in offspring. The prenatal period is considered to be the most crucial time for intervention.

Association between paternal age at childbirth and autism spectrum disorder in offspring. / çˆ¶äº²ç”Ÿè‚²å¹´é¾„ä¸Žå„¿ç«¥å­¤ç‹¬ç—‡è°±ç³»éšœç¢çš„ç›¸å ³æ€§.

OBJECTIVES: To study the association between paternal age at childbirth and the risk of autism spectrum disorder (ASD) in offspring. METHODS: In this cross-sectional study, 71 children with ASD who were diagnosed in the Department of Child Healthcare in six hospitals in Guangzhou, Foshan, Beijing, Wuhan, Hangzhou, and Chongqing of China from August 2016 to March 2017 were enrolled as subjects, and 284 typically developing children matched for age, sex, and maternal age at childbirth with the ASD children served as controls. A self-design questionnaire was used to collect the data on social demography, maternal pregnancy, and delivery. The association between paternal age at childbirth and the development of ASD in offspring was evaluated by the logistic regression analysis. RESULTS: After control for demographic factors and pregnancy- and delivery-related factors, the logistic regression analysis showed that a relatively high paternal age at childbirth was significantly associated with the increased risk of ASD in offspring (OR=1.12, 95%CI: 1.02-1.23, P<0.05). After grouping based on the paternal age, the logistic regression analysis showed that paternal age at childbirth of ≥40 years was significantly associated with the risk of ASD in offspring (before adjustment: OR=7.08, 95%CI: 1.77-28.32, P<0.05; after adjustment: OR=8.50, 95%CI: 1.71-42.25, P<0.05). CONCLUSIONS: High paternal age at childbirth is significantly associated with the increased risk of ASD in offspring, and paternal age at childbirth ≥40 years may be the high-risk age group for ASD in offspring.

The validity and reliability of the simplified Chinese version of the Social Communication Questionnaire.

This study aims to validate the simplified Chinese version of the Social Communication Questionnaire (SCQ) in children aged 2-12 years from both general and clinical populations. We recruited 819 Chinese children in this study, including 505 typically developing (TD) children, 202 children with autism spectrum disorder (ASD) and 112 children with non-ASD neurodevelopmental disorders. All the children's parents completed the simplified Chinese version of the SCQ and all children with ASD were additionally assessed for intelligence and the Childhood Autism Rating Scale to confirm their diagnosis. We have developed a 40-item, 4-factor structure of SCQ with two domains (social communication and social interaction; and restricted, repetitive, and stereotyped patterns of behavior), which showed adequate goodness of fit (comparative fit index [CFI] = 0.96, Tucker-Lewis index [TLI] = 0.95, standardized root mean squared residual [SRMR] = 0.07, root mean square error of approximation [RMSEA] = 0.05), with good internal consistency (Cronbach's alpha = 0.92). We have provided different cut-offs to distinguish ASD cases from TD children (11 for children under 4 years [sensitivity: 0.96, specificity: 0.95], 12 for children 4 years and above [sensitivity: 0.93, specificity: 0.98]) or children with other neurodevelopmental disorders (14 [sensitivity: 0.85, specificity: 0.88]). Through this large sample validation, we confirmed that the simplified Chinese version of the SCQ could be used for children aged 2-12 years with relatively good psychometric properties. LAY SUMMARY: We aimed to develop the simplified Chinese version of the Social Communication Questionnaire (SCQ) for Chinese children aged 2-12 years as a screening tool to identified potential risk of autism spectrum disorder (ASD). We have developed a 40-item, 4-factor structure of SCQ with two domains, which showed adequate goodness of fit and good psychometric properties. We also provided different cut-offs to identify ASD cases in general or clinical populations.

Reliability and Validity of the Chinese Version of Modified Checklist for Autism in Toddlers, Revised, with Follow-Up (M-CHAT-R/F).

Although early detection of autism facilitates intervention, early detection strategies are not yet widespread in China. To improve the situation, the Chinese version of the Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F) was validated. The sample included 7928 toddlers, aged 16 to 30 months, screened during their routine care in six provinces of China. When the cut-off value was 3, the sensitivity and specificity of M-CHAT-R were 0.963 and 0.865. The inter-rater reliability and the test-retest reliability were also adequate (intraclass correlation coefficients were 0.853 and 0.759, both ps < .01). The Chinese version of M-CHAT-R/F is an effective tool for early detection of ASD and is applicable to early screening in China.

[Developmental level of joint attention ability in children aged 16-30 months and related influencing factors].

OBJECTIVE: To investigate the developmental level of joint attention ability in children aged 16-30 months and factors influencing the developmental level. METHODS: A questionnaire survey was performed among 1 675 children aged 16-30 months who visited the Department of Child Health Care in Guangdong Women and Children's Hospital between September and December, 2016 to investigate their joint attention ability and related influencing factors. RESULTS: Of the 1 675 children, 1 579 (94.27%) had reactive joint attention ability at the age of 16-30 months, and 1 428 (85.25%) had active joint attention ability. The percentages of children with reactive joint attention ability and active joint attention ability in boys were lower than in girls (P<0.001). Mother's age, father's occupation, annual family income, way of conception, intended or unintended pregnancy, and mode of delivery were factors influencing the total score of joint attention ability and the scores of reactive/active joint attention ability (P<0.05). CONCLUSIONS: Most children have reactive joint attention ability and active joint attention ability at the age of 16-30 months. During this period of age, boys tend to have poorer joint attention ability than girls. Mother's age, father's occupation, annual family income, way of conception, intended or unintended pregnancy, and mode of delivery are associated with the development of joint attention.

Role of Gemcitabine and Pemetrexed as Maintenance Therapy in Advanced NSCLC: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Gemcitabine and pemetrexed have been used as maintenance therapy. However, few systematic reviews and meta-analyses have assessed their effects in the newest studies. This systematic review and meta-analysis were conducted to assess the role of gemcitabine and pemetrexed in the maintenance treatment of non-small-cell lung carcinoma (NSCLC). METHODS: We performed a literature search using PubMed, EMBASE and Cochrane library databases from their inceptions to September 16, 2015. We also searched the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and National Comprehensive Cancer Network (NCCN) databases from 2008 to 2015. Two authors independently extracted the data. The Cochrane Collaboration's risk of bias graph was used to assess the risk of bias. The GRADE system was used to assess the grading of evidence, and a meta-analysis was conducted using Stata 11.0 software. RESULTS: Eleven randomized controlled trial (RCT) studies were collected. Ten studies were included in the meta-analysis and divided into the following 4 groups: gemcitabine vs. best supportive care (BSC)/observation, pemetrexed vs. BSC/placebo, pemetrexed + bevacizumab vs. bevacizumab and pemetrexed vs. bevacizumab. Gemcitabine exhibited significantly improved progression-free survival (PFS) compared with BSC (hazard ratio (HR) = 0.62, p = 0.000). Pemetrexed exhibited significantly improved PFS (HR = 0.54, p = 0.000) and OS (HR = 0.75, p = 0.000) compared with BSC. Pemetrexed + bevacizumab almost exhibited significantly improved PFS (HR = 0.71, p = 0.051) compared with bevacizumab. Pemetrexed exhibited no improvement in PFS or overall survival (OS) compared with bevacizumab. Regarding the grade, the GRADE system indicated that the gemcitabine group was "MODERATE", the pemetrexed group was "HIGH", and both the pemetrexed + bevacizumab vs. bevacizumab groups and pemetrexed vs. B groups were "LOW". CONCLUSIONS: Gemcitabine or pemetrexed compared with BSC/observation/placebo significantly improved PFS or OS. Whether pemetrexed + bevacizumab compared with bevacizumab alone significantly improves PFS requires further investigation.

Efficacy of tamoxifen in combination with docetaxel in patients with advanced non-small-cell lung cancer pretreated with platinum-based chemotherapy.

The aim of this study was to evaluate the efficacy and safety of the combination of docetaxel (TXT) plus tamoxifen (TAM) in advanced non-small-cell lung cancer (NSCLC) patients who had received platinum-based first-line chemotherapy. A total of 120 advanced NSCLC patients pretreated with platinum-based chemotherapy were randomized into two treatment groups (the TXT and TXT+TAM groups) in a 1 : 1 ratio. Reversal of P-glycoprotein (P-gp) expression, tumor response, progression-free survival, overall survival, and safety were evaluated on an intention-to-treat basis. The median number of cycles of allocated chemotherapy was four in each treatment group (range: 2-6 cycles). The overall response rate and disease control rate in the TXT+TAM group were significantly higher than those in the TXT group (36.7 vs. 15.0% for overall response rate, P=0.007; 85.0 vs. 68.3% for disease control rate, P=0.031). The combination of TXT and TAM could effectively reverse P-gp expression in tumor tissues and provide a significant survival benefit for advanced NSCLC patients compared with TXT alone (11.6 vs. 9.1 months, P=0.030). In addition, in the TXT+TAM group, patients achieving P-gp reversal had a significantly greater median progression-free survival and overall survival than nonreversal patients. Furthermore, the combined therapy showed a safety profile comparable to that of TXT. The combination of TXT and TAM may be an effective and safe treatment option for advanced NSCLC patients who have already developed P-gp-mediated multidrug resistance.

Primary desmoplastic small round cell tumor of the testis: A case report and review of the literature.

Desmoplastic small round cell tumors (DSRCTs) are extremely rare and mainly affect adolescents and young adults. The tumors are usually involved with the abdominal area and/or the pelvic peritoneum. Only a small number of cases have been reported concerning DSRCTs of the testicular region. The present study reports a case of DSRCT of the testis with radical orchectomy and systemic chemotherapy, leaving the patient disease-free for 14 months. However, the patient died of multiple metastasis 12 months later. Furthermore there is a review of the English literature to analyze the incidence, site of origin, imaging and pathological characteristics of DSRCT.