Contribution of labor related gene subtype classification on heterogeneity of polycystic ovary syndrome.

OBJECTIVE: As one of the most common endocrine disorders in women of reproductive age, polycystic ovary syndrome (PCOS) is highly heterogeneous with varied clinical features and diverse gestational complications among individuals. The patients with PCOS have 2-fold higher risk of preterm labor which is associated with substantial infant morbidity and mortality and great socioeconomic cost. The study was designated to identify molecular subtypes and the related hub genes to facilitate the susceptibility assessment of preterm labor in women with PCOS. METHODS: Four mRNA datasets (GSE84958, GSE5090, GSE43264 and GSE98421) were obtained from Gene Expression Omnibus database. Twenty-eight candidate genes related to preterm labor or labor were yielded from the researches and our unpublished data. Then, we utilized unsupervised clustering to identify molecular subtypes in PCOS based on the expression of above candidate genes. Key modules were generated with weighted gene co-expression network analysis R package, and their hub genes were generated with CytoHubba. The probable biological function and mechanism were explored through Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. In addition, STRING and Cytoscape software were used to identify the protein-protein interaction (PPI) network, and the molecular complex detection (MCODE) was used to identify the hub genes. Then the overlapping hub genes were predicted. RESULTS: Two molecular subtypes were found in women with PCOS based on the expression similarity of preterm labor or labor-related genes, in which two modules were highlighted. The key modules and PPI network have five overlapping five hub genes, two of which, GTF2F2 and MYO6 gene, were further confirmed by the comparison between clustering subgroups according to the expression of hub genes. CONCLUSIONS: Distinct PCOS molecular subtypes were identified with preterm labor or labor-related genes, which might uncover the potential mechanism underlying heterogeneity of clinical pregnancy complications in women with PCOS.

An evaluation survey of traditional Chinese medicine learning among international students majoring in conventional medicine: a study from a university in China.

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.

Association between circadian rhythm disruption and polycystic ovary syndrome.

OBJECTIVE: To explore the association of circadian rhythm disruption with polycystic ovary syndrome (PCOS) and the potential underlying mechanism in ovarian granulosa cells (GCs). DESIGN: Multicenter questionnaire-based survey, in vivo and ex vivo studies. SETTING: Twelve hospitals in China, animal research center, and research laboratory of a women's hospital. PATIENTS/ANIMALS: A total of 436 PCOS case subjects and 715 control subjects were recruited for the survey. In vivo and ex vivo studies were conducted in PCOS-model rats and on ovarian GCs collected from women with PCOS and control subjects. INTERVENTION(S): The PCOS rat model was established with the use of testosterone propionate. MAIN OUTCOME MEASURE(S): Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), RNA sequencing, rhythmicity analysis, functional enrichment analysis. RESULT(S): There was a significant correlation between night shift work and PCOS. PCOS-model rats presented distinct differences in the circadian variation of corticotropin-releasing hormone, adrenocorticotropic hormone, prolactin, and a 4-h phase delay in thyrotropic hormone levels. The motif enrichment analysis of ATAC-seq revealed the absence of clock-related transcription factors in specific peaks of PCOS group, and RNA sequencing ex vivo at various time points over 24 hours demonstrated the differential rhythmic expression patterns of women with PCOS. Kyoto Encyclopedia of Genes and Genomes analysis further highlighted metabolic dysfunction, including both carbohydrate and amino acid metabolism and the tricarboxylic acid cycle. CONCLUSION(S): There is a significant association of night shift work with PCOS, and genome-wide chronodisruption exists in ovarian GCs.

Molecular mechanisms underlying altered neurobehavioural development of female offspring of mothers with polycystic ovary syndrome: FOS-mediated regulation of neurotrophins in placenta.

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.).

The evaluation of online course of Traditional Chinese Medicine for MBBS international students during the COVID-19 epidemic period.

BACKGROUND: During the COVID-19 epidemic period, Traditional Chinese Medicine (TCM) course for international students of Medical Bachelor, Bachelor of Surgery (MBBS) program in Zhejiang University has shifted from traditional classroom to online environment. This study aimed to investigate MBBS international students' perception on online TCM course, and to assess the online learning efficacy. METHODS: A total of 84 MBBS international students attending course of "Basic Traditional Chinese Medicine" during 2020 academic years at Zhejiang University were enrolled in this study. A quantitative questionnaire was respectively completed before and after the TCM course using a pretest-post-test design. By means of two online learning platforms, Learning in ZJU and DingTalk, TCM course was broadcast in both live and archived format to students. RESULTS: A total of 48 participants completed both baseline and follow-up questionnaires. The majority of participants preferred face-to-face classroom learning (26, 54.17% of total) when compared with online learning. Students felt that the course had brought in much benefits (mean 3.88, SD 0.87), and they were satisfied with the course content (mean 3.83, SD 0.95). Students' TCM related knowledge and their behaviors of discussion and consulting were significantly improved by online TCM course (all P < 0.001). Students' awareness of the necessity of TCM education and their feeling of difficulty in learning TCM were significantly strengthened (P = 0.042, 0.025, respectively). CONCLUSION: Online learning is a good alternative for TCM course of MBBS international students when classroom learning is suspended, whereas it cannot replace the need for onsite and face-to-face learning.

Artificial sweeteners affect the glucose transport rate in the Caco-2/NCI-H716 co-culture model.

BACKGROUND: Artificial sweeteners have been used widely as substitutes for sugar for several decades. In recent years they have been reported to be harmful to human health - especially to glucose absorption. However, as conclusions from previous studies using a single Caco-2 cell model were not consistent, further studies with a more suitable cell model are needed. RESULTS: We established a co-culture model with enterocyte Caco-2 and enteroendocrine NCI-H716 cell lines cultured in transwell inserts. The effects of artificial sweeteners, enhancing the glucose transport rate, lasted for 60 min and then began to diminish. Most importantly, different artificial sweeteners with the same sweetness intensity had similar effects on glucose transport. The sodium / glucose co-transporter member 1 (SGLT1) mRNA expression levels increased significantly with an initial glucose concentration of 20 mM, while glucose transporter 2 (GLUT2) mRNA expression significantly increased with initial glucose concentrations of 20 mM and 60 mM. CONCLUSION: Based on the Caco-2/NCI-H716 co-culture model, SGLT1 and GLUT2 mediated the enhancing effects of artificial sweeteners on glucose transport, depending on the sweetness intensity and initial glucose concentration.

The effects of acupuncture on pregnancy outcomes of in vitro fertilization with embryo transfer: An interdisciplinary systematic review.

The present systematic review is designed to summarize the evidence concerning the effect of acupuncture on pregnancy outcomes in vitro fertilization with embryo transfer (IVF-ET). We searched MEDLINE, the Wanfang Database, the China Academic Journal Electronic Full-text Database in the China National Knowledge Infrastructure, and the Index to Chinese Periodical Literature. Randomized controlled trials with intervention groups using acupuncture and control groups consisting of no acupuncture or sham (placebo) acupuncture in IVF-ET treatment were selected. Study characteristics were examined from these studies and an intention-to-treat approach was used to extract outcome data from each study. In total, 31 articles including 4450 women passed our selection criteria. The legitimacy, characteristics, and IVF outcomes of the included trials were summarized. Additional Traditional Chinese Medicine (TCM) theory-based, standardized, large-size, randomized, and multicenter trials are necessary prior to any conclusions being drawn on whether TCM can improve IVF outcomes.