Body composition in second trimester is associated with dyslipidemia in third trimester.

OBJECTIVE: The aim of this study was to examine the correlation between maternal body composition during the second trimester and the occurrence of dyslipidemia in the third trimester. METHODS: A cohort of 1508 pregnant women who underwent antenatal testing at Shanghai Sixth People's Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, were included in this study. Maternal body composition was assessed using bioimpedance analysis between 14 and 22 weeks of gestation. RESULTS: Among the 1508 participants, a total of 1420 individuals (94.2%) were diagnosed with dyslipidemia. Notably, there were significant differences in body composition between the normal lipid group and the dyslipidemia group. Logistic regression analysis revealed that various factors including BMI, total body water (TBW), intra-cellular water (ICW), extra-cellular water (ECW), percent body fat (PBF), visceral fat area (VFA), fat-free mass (FFM) and arm circumference (AC) during the second trimester were all found to be associated with dyslipidemia in the third trimester. CONCLUSION: The present study found that maternal body composition was associated with dyslipidemia. The BMI, TBW, ICW, ECW, PBF, VFA, FFM and AC in second trimester were associated with dyslipidemia in third trimester.

Associated factors of depression in primiparas with hypothyroidism during pregnancy.

This cross-sectional study aimed to explore the associated factors of depression in primiparas with hypothyroidism during pregnancy. The research subjects were 200 primiparas with hypothyroidism during pregnancy who were admitted to our hospital between December 2016 and December 2019. Self-rating depression scale scores were used to evaluate the depression, and the incidence of depression were examined. The data from all the subjects were collected to compare the differences between primiparas with hypothyroidism during pregnancy with and without depression. A logistic regression equation was used to analyze the influencing factors of depression in these patients. Of the 200 primiparas who took part in this study, 27 suffered from depression, accounting for 13.50%. There were differences in age, education level, economic income, sleep quality, and conjugal relations between the depressed and the nondepressed participants. When the above factors were included in the logistic regression equation, it was found that the odds ratio values for these factors were all >1, which indicated that they had an influence on maternal depression in primiparas with hypothyroidism during pregnancy. This study demonstrated that pregnancy-associated hypothyroidism in primiparas is affected by age, education level, economic income, sleep quality, and conjugal relations, all of which increase the incidence of depression. Relevant preventive measures should be provided in clinical practice to avoid the occurrence of depression.

IRX2 regulates endometrial carcinoma oncogenesis by transcriptional repressing RUVBL1.

Endometrial carcinoma (EC) is a rising concern among gynecological malignancies. Iroquois Homeobox 2 (IRX2), a member of the Iroquois homeobox gene family, demonstrates variable effects in different cancer types, emphasizing the need for extensive exploration of its involvement in EC progression. Utilizing TCGA and GEO databases, as well as performing immunohistochemistry (IHC) analysis on clinical samples, we assessed the expression levels of IRX2 and its promoter methylation in EC. To understand the functional roles of IRX2, we conducted various assays including in vitro CCK-8 assays, colony formation assays, cell invasion assays, and cell apoptosis assays. Moreover, we utilized in vivo subcutaneous xenograft mouse models. Additionally, we performed KEGG pathway and gene set enrichment analyses to gain insights into the underlying mechanisms. To validate the regulatory relationship between IRX2 and RUVBL1, we employed chromatin immunoprecipitation and luciferase reporter assays. Our results indicate significantly reduced levels of IRX2 expression in EC, correlating with higher histological grades, advanced clinical stages, and diminished overall survival. We observed that DNA methylation of the IRX2 promoter suppresses its expression in EC, with cg26333652 and cg11793269 playing critical roles as methylated sites. In contrast, ectopic overexpression of IRX2 substantially inhibits cell proliferation and invasion, and promotes cell apoptosis. Additionally, we discovered that IRX2 exerts negative regulation on the expression of RUVBL1, which is upregulated in EC and associated with a poorer prognosis. In conclusion, our findings indicate that decreased expression of IRX2 facilitates EC cell growth through the regulation of RUVBL1 expression, thereby contributing to the development of EC. Hence, targeting the IRX2-RUVBL1 axis holds promise as a potential therapeutic strategy for EC treatment.

Factors influencing functional near-infrared spectroscopy in postpartum depression: A cross-sectional study.

OBJECTIVE: To explore whether functional near-infrared spectroscopy (fNIRS) can aid in the early detection and diagnosis of postpartum depression. METHODS: The study was a cross-sectional survey that invited all women who sought postpartum health examination 42 days after childbirth between August 2020 and January 2021. Personal information, Edinburgh Postnatal Depression Scale (EPDS), and well as fNIRS results were collected. RESULTS: In all, 109 individuals agreed to participate and completed the examination in its entirety. The variance in integral and centroid values was not statistically significant across different subgroups of depression (P > 0.05). The difference in diagnosis of postpartum major depression between EPDS and fNIRS was statistically significant (P < 0.001). fNIRS results in postpartum depression diagnosis were substantially associated with gestational diabetes mellitus (P = 0.027), the number of pregnancies (P = 0.001), and postpartum body mass index (P = 0.035). CONCLUSION: fNIRS can provide an objective method for early detection and diagnosis of postpartum depression. Certain clinical conditions can have an effect on brain activity, which may result in postpartum depression. Additional high-quality study is required to establish strong evidence on the subject.

Effects of 5-aminolevulinic acid photodynamic therapy for cervical low-grade squamous intraepithelial lesions with HR-HPV infections.

Objective: To determine the effectiveness and safety of 5-aminolevulinic acid mediated photodynamic therapy (5-ALA PDT) in HR-HPV infected patients with cervical low-grade squamous intraepithelial lesions (LSIL) and to explore possible factors affecting treatment outcomes. Methods: This retrospective study included 96 patients with histologically confirmed cervical LSIL and high-risk human papillomavirus (HR-HPV) infection. They received 5-ALA PDT treatment once a week for a total of 3 courses. All patients were evaluated by cytology tests, HPV DNA assay, colposcopy, and biopsy at 2 weeks, 3 months, and 6 months checkpoint. The chi-square test were used to evaluate the differences in various clinical data, and a p value <0.05 was considered statistically significant. Results: At 2 weeks, 3 months, and 6 months checkpoint, colposcopies showed that the cervical iodine-unstained area under VILI (visual inspection with Lugol's iodine) significantly reduced (p < 0.01) with no structure changes. At 3 months and 6 months checkpoint, the pathological regression rate reached 87.5% (84/96) and 94.79% (91/96), while the HR-HPV clearance rates reached 80.21% (77/96) and 93.75% (90/96) respectively. We also examined the efficacy in the HPV 16/18-related group and non-HPV 16/18-related group. The HR-HPV clearance rate in the HPV16/18 group [94.87% (37/39)] was significantly higher than that of the non-HPV 16/18 group [70.17% (40/57)]. However, at 6 months after treatment, the clearance rate of the HPV 16/18 group [94.87% (37/39)] showed no statistical difference from the non-HPV 16/18 group [92.30% (53/57)]. Conclusion: Topical 5-ALA PDT can effectively eliminate HR-HPV infection and treat low-grade cervical squamous intraepithelial lesions, it offers an alternative treatment option for patients with LSIL, especially for those with fertility requirements and who wish to preserve cervical structure or function.

A new predictive model for the concurrent risk of diabetic retinopathy in type 2 diabetes patients and the effect of metformin on amino acids.

Objective: This study established a model to predict the risk of diabetic retinopathy (DR) with amino acids selected by partial least squares (PLS) method, and evaluated the effect of metformin on the effect of amino acids on DR in the model. Methods: In Jinzhou, Liaoning Province, China, we retrieved 1031 patients with type 2 diabetes (T2D) from the First Affiliated Hospital of Liaoning Medical University. After sorting the amino acids using the PLS method, the top 10 amino acids were included in the model. Multivariate logistic regression was used to analyze the relationship between different amino acids and DR. And then the effects of metformin on amino acids were explored through interaction. Finally, Spearman's rank correlation analysis was used to analyze the correlation between different amino acids. Results: After sorting by PLS, Gly, Pro, Leu, Lyr, Glu, Phe, Tyr, His, Val and Ser were finally included in the DR risk prediction model. The predictive model after adding amino acids was statistically different from the model that only included traditional risk factors (p=0.001). Metformin had a significant effect on the relationship between DR and 7 amino acids (Gly, Glu, Phe, Tyr, His, Val, Ser, p<0.05), and the population who are not using metformin and have high levels of Glu (OR: 0.44, 95%CI: 0.27-0.71) had an additive protection effect for the occurrence of DR. And the similar results can be seen in high levels of Gly (OR: 0.46, 95%CI: 0.29-0.75), Leu (OR: 0.48, 95%CI: 0.29-0.8), His (OR: 0.46, 95%CI: 0.29-0.75), Phe (OR: 0.24, 95%CI: 0.14-0.42) and Tyr (OR: 0.41, 95%CI: 0.24 -0.68) in population who are not using metformin. Conclusions: We established a prediction model of DR by amino acids and found that the use of metformin reduced the protective effect of amino acids on DR developing, suggesting that amino acids as biomarkers for predicting DR would be affected by metformin use.

Menopausal Symptoms and Sleep Quality in Women Aged 40-65 Years.

The study examined the relationship between menopausal symptoms and sleep disturbances and the related influencing factors. Methods. We recruited women aged 40-65 years who attended the menopause clinic at Shanghai Jiao Tong University's Sixth People's Hospital from February 2011 to November 2019. The Menopause Rating Scale (MRS) was used to collect women's menopausal symptoms, and the Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the subjects' sleep condition. We used logistic regression models to identify the relationship between menopausal symptoms and sleep quality. Results. A total of 1341 participants were recruited in this study. The most frequent three symptoms assessed by MRS were fatigue (72.9%), sleep disturbance (67%), and hot flashes with night sweats (65%). Participants' age was significantly associated with the severity of menopausal syndrome (P < 0.01). According to the PSQI sleep evaluation, 66.9 percent of participants had sleep disturbances (PSQI > 5). Logistic regression analysis revealed that women with mild, moderate, or severe menopausal syndrome had a 3-, 7-, and 17-fold increased chance of having sleep disturbances compared to women without menopausal syndrome. Conclusion. Women aged 40-65 years were found to have a significantly higher risk of menopausal syndrome and sleep disturbances.

Effects of dietary structure on the incidence of gestational diabetes mellitus and macrosomia.

OBJECTIVES: To explore the relationship between dietary structure and the incidence of gestational diabetes mellitus and macrosomia. MATERIAL AND METHODS: In this retrospective study, the diet records of pregnant women admitted to the Sixth People's Hospital affiliated to Shanghai Jiaotong University between August 2017 and August 2018 were collected with the approval of the local ethics committee. Corresponding medical and clinical information of pregnant women were obtained from the medical system. The relationship between diet structure and the incidence of gestational diabetes and macrosomia was analyzed. RESULTS: A total of 93 pregnant women with elevated blood sugar (including new gestational diabetes mellitus and diabetes mellitus with pregnancy) were enrolled. There were 21 newborns with macrosomia. The consumption of tofu was negatively correlated with the occurrence of macrophages. The consumption of pork eaten was negatively correlated with blood sugar levels two hours after eating. The consumption of vegetables was positively correlated with the blood glucose level one hour after eating. Eggs may increase triglycerides and blood sugar, which is an important inducer of pregnancy complicated with diabetes and macrosomia. CONCLUSIONS: The diet structure of pregnant women is correlated with the occurrence of diabetes mellitus and macrosomia in pregnancy. It is recommended to eat more potato and not fried noodles with edible oil and to eat more high-quality protein, such as vegetable protein and lean pork.

ADGRG1 enriches for functional human hematopoietic stem cells following ex vivo expansion-induced mitochondrial oxidative stress.

The heterogeneity of human hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) under stress conditions such as ex vivo expansion is poorly understood. Here, we report that the frequencies of SCID-repopulating cells were greatly decreased in cord blood (CB) CD34+ HSCs and HPCs upon ex vivo culturing. Transcriptomic analysis and metabolic profiling demonstrated that mitochondrial oxidative stress of human CB HSCs and HPCs notably increased, along with loss of stemness. Limiting dilution analysis revealed that functional human HSCs were enriched in cell populations with low levels of mitochondrial ROS (mitoROS) during ex vivo culturing. Using single-cell RNA-Seq analysis of the mitoROS low cell population, we demonstrated that functional HSCs were substantially enriched in the adhesion GPCR G1-positive (ADGRG1+) population of CD34+CD133+ CB cells upon ex vivo expansion stress. Gene set enrichment analysis revealed that HSC signature genes including MSI2 and MLLT3 were enriched in CD34+CD133+ADGRG1+ CB HSCs. Our study reveals that ADGRG1 enriches for functional human HSCs under oxidative stress during ex vivo culturing, which can be a reliable target for drug screening of agonists of HSC expansion.

RXR Negatively Regulates Ex Vivo Expansion of Human Cord Blood Hematopoietic Stem and Progenitor Cells.

Ex vivo expansion of human cord blood (CB) hematopoietic stem cells (HSCs) is one approach to overcome limited numbers of HSCs in single CB units. However, there is still no worldwide acceptable HSC ex vivo expansion system. A main reason is that we still have very limited knowldege regarding mechanisms underlying maintenance and expansion of CB HSCs. Here we report that retinoid X receptor (RXR) activity is of significance for CB HSC ex vivo expansion. RXR antagonist HX531 significantly promoted ex vivo expansion of CB HSCs and progenitor cells (HPCs). RXR agonist Bexarotene notably suppressed ex vivo expansion of CB HSCs. Activation of RXR by Bexarotene significantly blocked expansion of phenotypic HSCs and HPCs and expressed increased functional HPCs as assessed by colony formation induced by UM171 and SR1. In vivo transplantation experiments in immune-deficient mice demonstrated that HX531 expanded CB HSCs possess long-term reconstituting capacities, and Bexarotene treatment inhibited expansion of functional CB HSCs. RNA-seq analysis revealed that RXR regulates expression of FBP1 (a negative regulator of glucose metabolism) and many genes involved in differentation. ECAR analysis showed that HX531 significantly promoted glycolytic activity of CB CD34+ HSCs and HPCs. Our studies suggest that RXR is a negative regulator of ex vivo expansion of CB HSCs and HPCs.

Effect of extruded starches on the structure, farinograph characteristics and baking behavior of wheat dough.

Extruded wheat starch (ES) was obtained by a single-screw extruder to determine its effect on the farinograph, structural properties and baking behaviors of wheat dough. XRD analysis showed that increasing extrusion temperature made the crystalline peaks less pronounced due to the partial gelatinization. In terms of FTIR results, the molecular order of extruded starch was lower than that of native starch. The dough development time was decreased from 3.2 min to 2.7 min while the stability time was increased from 14.4 min to 15.5 min, as 70 ES were added. It was accompanied with increasing levels of α-helix and ß-turn transferred from the decreased content of random coil and ß -sheet. These effects in bread were to increase loaf volume and reduced loaf hardness. These results indicated that extruded starch had a good potential for producing a high-quality bread.

Preeclampsia serum increases CAV1 expression and cell permeability of human renal glomerular endothelial cells via down-regulating miR-199a-5p, miR-199b-5p, miR-204.

INTRODUCTION: To gain insight into mechanisms of preeclampsia (PE)-dependent proteinuria, this study focused on whether preeclampsia serum (PES) could induce hyperpermeability in human renal glomerular endothelial cells (HRGECs) via the miRNAs-Caveolin-1 (CAV-1)-dependent pathway. METHODS: Bioinformatics approach was used to identify miRNAs targeting CAV1. Normal pregnancy serum (NPS) and severe PES were used to treat HRGECs monolayer to demonstrate if PES could induce the expression of identified miRNAs. A luciferase reporter assay was used to determine whether CAV1 was a direct target of miR-199a-5p, miR-199b-5p, and miR-204. The relationship between the expression of miR-199a-5p, miR-199b-5p, miR-204, and CAV1 in HRGECs was determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. The gain-of-function and loss-of-function experiments were performed on HRGECs to investigate the effects of miR-199a-5p, miR-199b-5p, miR-204 on HRGECs permeability. RESULTS: We identified that CAV1 3'UTR has putative binding sites for miR-199a-5p, miR-199b-5p, and miR-204, whereas miR-199a-5p does not appear to be a direct regulator of CAV1. We detected that PE serum downregulated the expression of miR-199a-5p, miR-199b-5p and miR-204, increased expression of CAV1 and increased cell monolayer permeability in HRGECs. The level of CAV1 and permeability decreased when miR-199b-5p or miR-204, but not miR-199a-5p, were overexpressed. DISCUSSION: miR-199b-5p and miR-204 may play a role in PES-induced increasing permeability of HRGECs by regulating CAV1 expression.

MELK promotes Endometrial carcinoma progression via activating mTOR signaling pathway.

BACKGROUND: Endometrial carcinoma (EC) is one of the most common gynecological malignancies among women. Maternal embryonic leucine Zipper Kinase (MELK) is upregulated in a variety of human tumors, where it contributes to malignant phenotype and correlates with a poor prognosis. However, the biological function of MELK in EC progression remains largely unknown. METHODS: We explored the MELK expression in EC using TCGA and GEO databases and verified it using clinical samples by IHC methods. CCK-8 assay, colony formation assay, cell cycle assay, wound healing assay and subcutaneous xenograft mouse model were generated to estimate the functions of MELK and its inhibitor OTSSP167. qRT-PCR, western blotting, co-immunoprecipitation, chromatin immunoprecipitation and luciferase reporter assay were performed to uncover the underlying mechanism concerning MELK during the progression of EC. FINDINGS: MELK was significantly elevated in patients with EC, and high expression of MELK was associated with serous EC, high histological grade, advanced clinical stage and reduced overall survival and disease-free survival. MELK knockdown decreased the ability of cell proliferation and migration in vitro and subcutaneous tumorigenesis in vivo. In addition, high expression of MELK could be regulated by transcription factor E2F1. Moreover, we found that MELK had a direct interaction with MLST8 and then activated mTORC1 and mTORC2 signaling pathway for EC progression. Furthermore, OTSSP167, an effective inhibitor, could inhibit cell proliferation driven by MELK in vivo and vitro assays. INTERPRETATION: We have explored the crucial role of the E2F1/MELK/mTORC1/2 axis in the progression of EC, which could be served as potential therapeutic targets for treatment of EC. FUNDING: This research was supported by National Natural Science Foundation of China (No:81672565), the Natural Science Foundation of Shanghai (Grant NO:17ZR1421400 to Dr. Zhihong Ai) and the fundamental research funds for central universities (No: 22120180595).

A long noncoding RNAs signature to improve survival prediction in endometrioid endometrial cancer.

PURPOSE: The dysregulation of long noncoding RNAs (lncRNAs) has been reported to be correlated to carcinogenesis and cancer progression. Endometrial cancer (EC), arising from the endometrium or the inner lining of the uterus, is one of the most common gynecological malignancies. We aim to explore the prognostic value of the lncRNAs in patients with endometrioid endometrial cancer (EEC) and to identify the potential lncRNA signature for predicting survival of patients with EEC. METHODS: We performed a genome-wide analysis of the lncRNA expression profiling in The Cancer Genome Atlas (TCGA)-Uterine Corpus Endometrial Carcinoma database (408 EEC) to identify the prognosis related lncRNAs for the EEC. The patients with EEC were randomly divided into a training set (204 for endometrioid) and a testing set (204 for endometrioid). The lncRNA signature was identified in the training set, and then independently validated in the testing set and the complete set (training set plus testing set). RESULTS: We developed a nine-lncRNA signature-based risk score in the patients with EEC. The risk score based on the novel lncRNAs signature was able to separate patients of training set into high-and low-risk groups with significantly different overall survival and progression-free survival. These can also be successfully confirmed in the testing set and complete set. CONCLUSION: A nine-lncRNA expression signature was identified and validated which can predict EEC patient's survival. These findings may have important implications in the understanding of the potential therapeutic methods for patients with EEC.

Preeclampsia serum induces human glomerular vascular endothelial cell hyperpermeability via the HMGB1-Caveolin-1 pathway.

To explore new ideas about the pathogeny of preeclampsia (PE) proteinuria, this study focused on whether severe PE serum (PES) could induce high-molecular-weight protein (HMWP) hyperpermeability in glomerular endothelial cells (GEC) via the HMGB1-Caveolin-1 (CAV-1) pathway. Normal pregnancy serum (NPS) and severe PES were used to treat primary human GEC monolayer for 24 h. The CAV-1 inhibitor methyl-beta-cyclodextrin (MBCD), the HMGB1 inhibitor glycyrrhizicacid (GA), recombinant HMGB1 (rHMGB1) were also used to treat GEC monolayer that were stimulated by NPS or severe PES. The dynamic permeability of GEC to HMWP was detected by Evans blue-labeled BSA and CAV-1 expression in GEC was analyzed by immunofluorescence staining and Western blotting. We detected HMGB1 expression in placenta and serum in normal pregnancy and severe PE. The results showed that severe PES significantly promoted GEC hyperpermeability and CAV-1 expression. By inhibiting CAV-1 expression, MBCD reversed severe PES-induced GEC monolayer permeability. HMGB1 expression in PE placenta and serum was significantly increased. Compared with that in normal placenta, HMGB1expression was increased in the cytoplasm of syncytiotrophoblast cells in PE placenta. GA decreased the severe PES-induced hyperpermeability and CAV-1 expression in GEC. rHMGB1 induced high expression levels of CAV-1 and HMWP hyperpermeability in GEC. In conclusion, HMGB1 is increased in severe PE patients and induces the expression of CAV-1 in GEC. High expression of CAV-1 in GEC can promote HMWP hyperpermeability, which may contribute to the development of PE proteinuria.

RelB/NF-κB links cell cycle transition and apoptosis to endometrioid adenocarcinoma tumorigenesis.

Dysfunction of nuclear factor-κB (NF-κB) signaling has been causally associated with numerous human malignancies. Although the NF-κB family of genes has been implicated in endometrial carcinogenesis, information regarding the involvement of central regulators of NF-κB signaling in human endometrial cancer (EC) is limited. Here, we investigated the specific roles of canonical and noncanonical NF-κB signaling in endometrial tumorigenesis. We found that NF-κB RelB protein, but not RelA, displayed high expression in EC samples and cell lines, with predominant elevation in endometrioid adenocarcinoma (EEC). Moreover, tumor cell-intrinsic RelB was responsible for the abundant levels of c-Myc, cyclin D1, Bcl-2 and Bcl-xL, which are key regulators of cell cycle transition, apoptosis and proliferation in EEC. In contrast, p27 expression was enhanced by RelB depletion. Thus, increased RelB in human EC is associated with enhanced EEC cell growth, leading to endometrial cell tumorigenicity. Our results reveal that regulatory RelB in noncanonical NF-κB signaling may serve as a therapeutic target to block EC initiation.

Pulsatility index in combination with biomarkers or mean arterial pressure for the prediction of pre-eclampsia: Systematic literature review and meta-analysis.

INTRODUCTION: Our objective was to perform a meta-analysis examining the sensitivity of pulsatility index (PI) and various biomarkers and PI and mean arterial pressure (MAP) for the prediction of pre-eclampsia. MATERIAL AND METHODS: PubMed, CENTRAL, and Embase databases were searched from inception until 8 May 2014 using combinations of the search terms: pre-eclampsia, ultrasonography, pregnancy, biomarker, mean arterial pressure, placental protein 13, pregnancy-associated plasma protein-A, placental growth factor, activin A, inhibin A, pulsatility index. The pooled sensitivity of PI + biomarkers and PI + MAP were calculated, and reported with corresponding 95% confidence intervals (CIs). RESULTS: Fifteen studies were included in the meta-analysis. The pooled sensitivity of all biomarkers for the prediction of pre-eclampsia was 0.669 (95% CI 0.610-0.723), for the prediction of early-onset pre-eclampsia was 0.830 (95% CI 0.794-0.861), and for the prediction of late-onset pre-eclampsia was 0.564 (95% CI 0.499-0.627). Similarly, the predictive ability of PI + MAP for early-onset pre-eclampsia was good (sensitivity 0.894), while that for late-onset was poor (sensitivity 0.570). CONCLUSION: The combination of PI and different biomarkers or MAP exhibits a good predictive ability for early-onset pre-eclampsia, and poor predictive ability for late-onset pre-eclampsia.