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Background This study explored the mechanisms underlying altered neurobehavioural development of female offspring born to mothers with polycystic ovary syndrome (PCOS). Methods In total, 20 women with PCOS and 32 healthy women who underwent caesarean deliveries with a single female foetus were recruited. Infants were assessed with Dubowitz scoring. Swan71 cell line with stable FOS overexpression was used to verify the regulatory effects of FOS on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) expression. Learning and memory in female first-generation (F1) and second-generation (F2) offspring in a rat model of PCOS was tested using the Morris water maze at puberty and adulthood. Transcriptome analysis of pubertal hippocampi and hypothalami of female F1 offspring was conducted. Findings Total score and behaviour subscales of Dubowitz scoring were significantly lower in female infants of women with PCOS. FOS and NGF protein levels were downregulated in placental villi of the PCOS group. FOS played a key role in BDNF inhibition and enhancing NGF in Swan71 cells. PCOS female F1 rats exhibited lower target crossing times during puberty when compared to controls. Transcriptome analysis revealed significant changes in hippocampal and hypothalamic neuronal pathways in female F1 rats at puberty. Interpretation FOS regulation of neurotrophins in the placenta negatively affects neurobehavioural development of female offspring of PCOS mothers. Funding This study was funded by the National Key R&D Program of China (2018YFC1004900 to F.Q. and F.W.) and the National Natural Science Foundation of China (81874480 to F.Q.; 81873837 to F.W.).

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Background Traditional Chinese medicine (TCM) has gained increasing acceptance and popularity by the global community. The current study aimed to investigate self-reported evaluations of learning TCM and opinions about TCM courses among undergraduate international students majoring in conventional medicine at a university in China. Methods A cross-sectional survey was conducted at the Zhejiang University School of Medicine. A self-reported questionnaire was administered to international undergraduates who were enrolled in the TCM course during the 2018 and 2019 academic years (n = 157). The course employed a student-centered, multiform learning model. Demographic data and self-reported evaluations of TCM learning background and TCM learning course were obtained to conduct the analysis. Results A total of 133 students responded to the questionnaire. Among the respondents, 21.0% had some TCM-related knowledge, and 51.1% were interested in learning TCM before the course. Ninety-six students (85.7%) were from Asia. Students from Thailand showed significantly more interest in learning TCM than did students from other Asian countries (p = 0.025). After the course, 77.2% of students agreed that the course had brought about many benefits, 86.4% were satisfied with the course content, and 77.3% were satisfied with the teaching method. Students expressed their willingness to further learn acupuncture and to obtain more skilled practice through more visualized learning methods. Conclusions The majority of the international students we surveyed agreed that the TCM course improved their interest in and understanding of TCM. It is thus suggested that TCM education should be directed toward students’ learning barriers and needs.

BackgroundIn rodents, hypothalamic brain-derived neurotrophic factor (BDNF) expression appears to be regulated by melanocortin-4 receptor (MC4R) activity. The impact of MC4R genetic variation on circulating BDNF in humans is unknown.ObjectiveTo compare BDNF concentrations of subjects with loss-of-function (LOF) and gain-of-function (GOF) MC4R variants to those of controls with common sequence MC4R.MethodsCirculating BDNF was measured in two cohorts with known MC4R sequence: 148 subjects of Pima Indian heritage ([mean±SD]: age 15.7±6.5y, BMI-Z 1.63±1.03), and 69 subjects of Hispanic heritage (10.8±3.6y, BMI-Z 1.57±1.07). MC4R variants were characterized in vitro by cell surface expression, receptor binding, and cAMP response after agonist administration. BDNF single nucleotide polymorphisms (SNPs) rs12291186, rs6265, and rs7124442 were also genotyped.ResultsIn the Pima cohort, no significant differences in serum BDNF was observed for 43 LOF-subjects versus 65 LOF-matched controls [age-, sex-, and BMI-matched] (P=0.29), or 20 GOF-subjects versus 20 GOF-matched controls (P=0.40). Serum BDNF was significantly associated with genotype for BDNF rs12291186 (P=0.006) and rs6265 (P=0.009), but not rs7124442 (P=0.99); BDNF SNPs did not interact with MC4R status to predict serum BDNF. In the Hispanic cohort, plasma BDNF was not significantly different among 21 LOF-subjects, 20 GOF-subjects, and 28 controls (P=0.79); plasma BDNF was not predicted by BDNF genotype or BDNF-x-MC4R genotype interaction.ConclusionsCirculating BDNF concentrations were not significantly associated with MC4R functional status, suggesting that peripheral BDNF does not directly reflect hypothalamic BDNF secretion and/or that MC4R signaling is not a significant regulator of the bulk of BDNF expression in humans.