Assessing the reproducibility and validity of a food frequency questionnaire for pregnant women from the Chinese Miao ethnic group.

Background: Currently, no food frequency questionnaire is available to be administered exclusively to ethnic minorities in China. This study aimed to evaluate the reproducibility and validity of a culturally tailored semi-quantitative food frequency questionnaire (FFQ) designed for pregnant women belonging to the Miao ethnic group in China. Methods: A total of 74 questions in the FFQ were administered to collect dietary information from Miao women in China during their pregnancy. This study included 153 and 127 pregnant women, respectively, for testing the validity and reproducibility of the results. Baseline FFQ data (FFQ1) were collected initially, followed by the administration of a repeated FFQ 4-6 weeks later (FFQ2). Two 24-h recalls (24HR) were used as references to compare food groups and nutrient intake. Pearson/Spearman's coefficients were used to measure the validity and reproducibility of the FFQ. Quartile cross-classification, weighted kappa coefficients, and Bland-Altman plots were employed to assess the agreement. Results: Most food groups and nutrient intake estimated by the FFQ were higher than those estimated by the 24HR. Food groups and nutrients' correlations for FFQ vs. 24HR after being energy-adjusted and de-attenuated, respectively, were 0.10 (vegetables) to 0.45 (grains/tubers) and 0.15 (iron) to 0.52 (riboflavin). Comparatively, correlation coefficients for FFQ1 vs. FFQ2 ranged from 0.41 (fruit) to 0.71 (vegetables) and from 0.45 (energy) to 0.64 (calcium). The percentage of pregnant women classified in the same or adjacent quartiles ranged from 64.08% (vegetables) to 95.29% (sour soup) and from 68.88% (vitamin E) to 78.81% (energy). Weighted kappa coefficients exceeded 0.2 for food groups and most nutrients, and Bland-Altman plots demonstrated acceptable agreement between the two tools. Conclusions: This study provides novel information on the validation of FFQ. It demonstrates that the FFQ exhibits ideal reproducibility and acceptable validity in estimating and ranking the intake of food groups and most nutrients among pregnant women belonging to the Chinese Miao ethnic group.

Association between screen time and physical activity on mental health among preschoolers: a cross-sectional study from Southwest China.

BACKGROUND: Screen time and physical activity behaviors undergo development during early childhood and impact mental health. However, there is limited knowledge regarding the associations between physical activity, screen time, and mental health problems (MHP) in preschoolers. This study examines these associations using a large sample size and brief measures. METHODS: A multistage cluster stratified sampling method was used to conduct an observational cross-sectional study of 19,015 Chinese preschoolers in 2020. Information on physical activity, and screen time was collected by a self-administered questionnaire; MHP was assessed by the parent-reported Strengths and Difficulties Questionnaire (SDQ). Logistic regression models were used to obtain the odds ratios (ORs) and 95% confidence intervals (95% CIs) of preschoolers' MHP associated with screen time, total physical activities, moderate to vigorous physical activity (MVPA), and outdoor physical activities. RESULTS: A total of 19,015 participants from the 19,548 recruited population were included in the analyses (missing rate: 2.73%), 52.60% were boys. 64.01%, 57.96%, 35.98%, and 82.64% of preschoolers were reported to meet total physical activities, MVPA, and outdoor activities with screen time recommendations level. The results of multivariable-adjusted ORs (95% CIs) of preschoolers' MHP for comparisons of different levels of screen time (< 2 h/day, 2-4 h/day,≥4 h/day) show that screen time positively associated with MHP after adjusting for confounders (P < 0.05), but the association was not significant among girls with screen time ≥ 4 h/day. In addition, increased engagement in physical activity was reversely linked to MHP (P < 0.05). A stronger association between MHP and MVPA was observed in boys, however, this association was weakened when the total time spent engaging in MVPA exceeded two hours per day (P < 0.05). CONCLUSION: Less physical activity and more screen time positively relate to MHP, but the relationship differs by type of physical activity, total time, and gender. These findings provide novel insights and evidence supporting for guidelines on physical activity, screen time, and improvement of mental health for preschoolers.

Neferine mediated TGF-ß/ERK signaling to inhibit fibrosis in endometriosis.

OBJECTIVE: To investigate the mechanism of Neferine in treating endometriosis fibrosis by TGF-ß/ERK signaling pathway through a combination of network pharmacological analysis of Lotus embryos, in vivo animal experiments, and in vitro cell experiments. METHODS: The active ingredients of the drug lotus embryos, the drug targets and the targets of endometriosis were determined from the TCMSP database, the Swiss Target Prediction database and GeneCard and Online Mendelian Inheritance in Man. The String database and Cytoscape 3.6.3 software were used to construct the network of common target protein interactions between drug and disease, as well as the target network. GO and KEGG enrichment analysis of the common targets was performed. We designed endometriosis mouse models with Neferine to investigate the therapeutic effect of Neferine on the fibrosis model of endometriosis and its mechanism of action. Different methods were used to evaluate the treated endometriotic lesion tissue and the untreated ectopic lesion tissue. The 12Z cells (human endometriosis immortalized cells) were cultured in vitro and treated with Neferine to detect cell viability and the effects of invasion and metastasis. RESULTS: The results of GO function and KEGG enrichment analysis showed that the role pathways of lotus germ were TGF-ß signaling pathway, ERK1/2 signaling pathway, IL-17 signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway, and PI3K-Akt signaling pathway. Neferine which is one of the effective active ingredients of lotus germ, significantly inhibited the expression of fibronectin, collagen I, connective tissue growth factor, and smooth muscle actin by activating the TGF-ß/ERK pathway in vivo, which is required for the fibrosis process of endometriosis. Neferine also significantly inhibited the proliferation, invasion and metastasis ability of 12Z cells. CONCLUSION: Neferine inhibits the progression of endometriosis both in vitro and in vivo. Its mechanism of action may involve the regulation of the TGF-ß/ERK signaling pathway, leading to the inhibition of fibrosis in endometriosis.

Mechanism of Thunberg Fritillaria in treating endometriosis based on network pharmacology and the effect of Peiminine on the MEK/ERK pathway.

OBJECTIVE: To explore the mechanism of Thunberg Fritillaria in treating endometriosis (EMs) based on network pharmacology and the effect of Peiminine on the MEK/ERK pathway. METHODS: We applied Chinese medicine system pharmacology analysis platform (TCMSP) database and literature search to screen the main chemical components of Fritillaria thunbergii Miq and created a Vanny map from the databases of TCMSP, GENECARDS, Online Mendelian Inheritance in Man (OMIM), and some others. The STRING database was used to construct the protein interaction network of Fritillaria thunbergii Miq and EMs. The overlapping targets and enriched pathways were discovered using the cells of the innate immune annotation database (DAVID) and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. To test the mechanism of Peiminine, the active ingredients of Fritillaria thunbergii, in the therapy of EMs, we designed cell assays and animal research. EMs mouse models were treated with several therapies, including fibrosis inhibitor in Peiminine by utilizing Hematoxylin-eosin staining (HE staining), MASSON staining, Immunohistochemistry, Immunofluorescence, quantitative real-time PCR (qRT-PCR) experiment, and Western blotting test. We evaluated the anti-endometriotic effects of Peiminine using 12Z human endometriotic cells. Cell Counting Kit 8 was used to assess the vitality of 12z cells (CCK8). We evaluated the migration ability of 12z cells by cell scratch test. RESULTS: The effective active ingredients of Fritillaria thunbergii Miq in the treatment of EMs are Pelargonidin, Beta-sitosterol syringaresinol, Peimisine Pelargonidin-3, 5-diglucoside Ziebeimine Zhebeiresinol Verticine Solatubin OSI-2040 Chaksine Peiminine Peiminoside Peiminoside_qt, and 6-Methoxyl-2-acetyl-3-methyl-1, 4-naphthoquinone-8-O-beta-D-glucopyranoside. The critical targets for Fritillaria thunbergii Miq treating EMs are NOS2/PTGS1/AR/PPARG/PTGS2/NCOA2/RXRA/PGR/NR3C1/NCOA1/SLC6A4/OPRM1/BCL2 and ESR1. The results of GO function and KEGG enrichment analysis showed that the role pathway was estrogen-related signaling and thyroid hormone-related signaling. The expression of E-cadherin was decreased in EMs while MEK1/2, P-ERK, N-cadherin and vimentin were all increased in MASSON, immunofluorescence, Real-time PCR and Western blotting. In epithelial 12Z cells, high concentrations of Peiminine can block cell activity and migration, which is directly related to blocking cell fibrosis. CONCLUSION: Overall, this study partially verified the network pharmacological prediction that Peiminine regulates the MAPK pathway in inhibiting 12Z cell proliferation and migration, and finally protects against EMs.

Cryptotanshinone Protects against PCOS-Induced Damage of Ovarian Tissue via Regulating Oxidative Stress, Mitochondrial Membrane Potential, Inflammation, and Apoptosis via Regulating Ferroptosis.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age. Cryptotanshinone (CRY) has been shown to be effective in reversing reproductive disorders, but whether it can be used in the treatment of polycystic ovary syndrome remains unclear. We aimed to explore whether the mechanism of cryptotanshinone (CRY) in the treatment of polycystic ovary syndrome (PCOS) can be driven via regulating ferroptosis. A rat model of PCOS was established by daily injection of human chorionic gonadotropin and insulin for 22 days. An in vitro model of ischemia-reperfusion (IR) of granulosa cells was established. The in vitro and rat models of PCOS were subjected to different treatments including ferroptosis activators and inhibitors, CRY, and MAPK inhibitor. Oxidative stress was evaluated by measuring the activities of SOD, MDA, and GSH-PX. Total body weight and ovarian weight, as well as the levels of LH and the LH to FSH ratio, significantly increased in rats with PCOS, compared with controls. The expression of Bax was increased in PCOS tissues while PGC1α, NFR1, GPX4, catalase p-ERK, and Bcl-2 were all downregulated. Ferroptosis activator, erastin, had effects similar to those of PCOS while the contrary was found with CRY and ferroptosis inhibitor treatment groups. In vitro, CRY inhibited oxidative stress, MMP, and NF-κB and activated MAPK/ERK signaling by regulating ferroptosis. Overall, this study indicated that CRY protects against PCOS-induced damage of the ovarian tissue, via regulating oxidative stress, MMP, inflammation, and apoptosis via regulating ferroptosis.

Tanshinone for polycystic ovary syndrome: A protocol of systematic review and meta-analysis.

BACKGROUNDS: Polycystic ovary syndrome (PCOS) constitutes an endocrine and metabolic disorder characterized by hyperandrogenemia, ovulation disorders, and polycystic ovary. Existing therapy is low efficacy and has significant side effects. In traditional Chinese medicine, tanshinone was used for PCOS women. Here, we will investigate the safety, as well as the efficacy of tanshinone in treating polycystic ovary syndrome. METHODS: Two researchers will independently research eligible randomized controlled trials in 6 repositories: PubMed, CINAHL, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), as well as Cochrane Library, from their onset to present. The languages will constitute either English or Chinese, and we will carry out article selection, data mining, and conduct an evaluation of the risk of bias by the Cochrane tool of risk of bias. All analyses will be conducted by using the Cochrane Review Manager software (RevMan 5.3). RESULTS AND CONCLUSION: This study will provide the latest research evidence on the efficacy, as well as safety of tanshinone for PCOS patients. REGISTRATION NUMBER: INPLASY2020100017.

Cryptotanshinone alleviates polycystic ovary syndrome in rats by regulating the HMGB1/TLR4/NF­κB signaling pathway.

Cryptotanshinone (CRY) has been demonstrated to reverse reproductive disorders. However, whether CRY is effective in the treatment of polycystic ovary syndrome (PCOS) remains unknown. The aim of the present study was to evaluate the therapeutic potential of CRY in PCOS. A rat model of PCOS was established by daily injection of human chorionic gonadotropin and insulin for 22 days. Total body weight and ovarian weight, as well as the levels of luteinizing hormone (LH) and the LH to follicle­stimulating hormone (FSH) ratio (LH/FSH) significantly increased in rats with PCOS, compared with controls. Moreover, the levels of testosterone (T), tumor necrosis factor (TNF)­α and high­mobility group box 1 protein (HMGB1) also increased. However, CRY treatment attenuated the increase in body weight, ovarian weight, LH, LH/FSH ratio, T, TNF­α and HMGB1 levels, compared with the PCOS group. Treatment with CRY also reduced NF­κB/p65, HMGB1 and toll­like receptor (TLR)4 mRNA and protein expression levels in the ovarian tissue and granulosa cells, both in vitro and in vivo. Thus, CRY significantly mitigated the changes in body weight, ovary weight, hormone levels and inflammatory factor levels observed in rats with PCOS. Thus, CRY protects against PCOS­induced damage of ovarian tissue, possibly through a regulatory pathway involving HMGB1, TLR4 and NF­κB.

Ginsenoside Rg1 impairs homologous recombination repair by targeting CtBP-interacting protein and sensitizes hepatoblastoma cells to DNA damage.

The ginsenoside Rg1, the primary pharmacologically active ingredient of the traditional Chinese herb ginseng, is widely used in the clinical treatment of diseases of the immune and nervous systems. Recent studies have shown that it also has an antitumor effect. In this study, we explored the effects of Rg1 on hepatoblastoma (HB) and its underlying mechanisms. We demonstrated that Rg1 significantly inhibited HB cell growth both in vivo and in vitro. Mechanistic studies revealed that Rg1 impaired homologous recombination and triggered double-strand breaks in HB cells by directly targeting CtBP-interacting protein (CtIP), a key double-strand break repair factor, which is highly expressed in HB tissues. Moreover, we also demonstrated that Rg1 sensitized HB cells to DNA-damaging agents both in vitro and in vivo. In conclusion, our data not only demonstrate the potential clinical application of Rg1 as a novel chemotherapeutic candidate but also offer a mechanism-based therapeutic option by which DNA-damaging agents can be used in combination with Rg1 to target HB.

Isoorientin triggers apoptosis of hepatoblastoma by inducing DNA double-strand breaks and suppressing homologous recombination repair.

Hepatoblastoma (HB) is the most common malignant liver tumor in children. DNA and DNA-associated processes are one of the most important targets of chemotherapeutic agents. Isoorientin (Iso), a natural flavonoid compound, can be extracted from several plant species. The effects of Iso and its molecular mechanisms on hepatic malignancies remain unclear. Herein, the anti-tumor effects of Iso in HB and its underlying mechanisms were explored. We found that Iso significantly inhibited the proliferation of HB cells both in vitro and in vivo. Mechanistic studies showed that Iso triggered cell apoptosis by inducing DNA double-stranded breaks and blocking the initiation process of homologous recombination repair, which was related to the attenuation of ataxia telangiectasia mutated (ATM) activation and inhibiting the binding of phosphorylated ataxia telangiectasia mutated (pATM) and the MRE11-RAD50-NBS1 (MRN) complex. Furthermore, Iso markedly sensitized HB cells to the anti-proliferative effects of the poly ADP-ribose polymerase (PARP) inhibitor olaparib both in vivo and in vitro. Taken together, our study first showed that Iso was a DNA-damage agent, and the combination of Iso with a PARP inhibitor might be a promising strategy for treating HB patients.

High concentration of insulin promotes apoptosis of primary cultured rat ovarian granulosa cells via its increase in extracellular HMGB1.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age. Insulin resistance/hyperinsulinemia is a prevalent finding in women with PCOS, which indicates that insulin resistance/hyperinsulinemia may be an important player in the pathogenesis of the PCOS. However, the underlying mechanism of insulin resistance/hyperinsulinemia on the pathogenesis of the PCOS remains elusive. In this study, we found an increased high-mobility group box 1 (HMGB1) in the serum from women with PCOS having insulin resistance/hyperinsulinemia. Furthermore, we discovered that high concentration of insulin, which mimics insulin resistance model, promoted apoptosis in primary cultured rat ovarian granulosa cells (GCs) via its effect on the increase in extracellular HMGB1. Our data presented the first evidence that increased HMGB1 induced by insulin resistance/hyperinsulinemia promoted apoptosis of ovarian GCs, which provided new molecular basis for the PCOS pathogenesis.