Sympathetic hyperactivity is a key feature of cardiovascular dysfunction in postmenopausal women and is closely linked to the onset, progression, and outcomes of cardiovascular events. However, the mechanisms underlying sympathetic nerve hyperactivity due to menopause remain unclear. (3-arrestin is a versatile class of intracellular proteins that were initially discovered for their ability to disrupt the G protein-coupled receptors (GPCRs) signaling by binding to activated receptors. A notable reduction in the expression of (3-arrestin1 in the rostral ventrolateral medulla (RVLM) associated with increased sympathetic activity and elevated blood pressure (BP) in spontaneously hypertensive rats. It has been reported that the cellular oncogene fos (cFos), as a transcription factor, plays a crucial role in BP regulation. This study aimed to investigate whether (3-arrestin1, regulated by cFos in the RVLM, contributes to sympathetic hyperactivity induced by menopause. Bilateral ovariectomy (OVX) was performed to establish a postmenopausal rat model. We found that the expression of (3-arrestin1 in the RVLM of OVX rats was reduced, whereas estrogen supplementation increased the expression of (3-arrestin1. Furthermore, overexpression of (3-arrestin1 in the RVLM of OVX rats attenuated the sympathetic hyperactivity. Conversely, reducing (3-arrestin1 expression in the RVLM compromised the cardioprotective effects of estrogen in OVX rats. Additionally, inhibiting the expression of the transcription factor cFos in the RVLM of OVX rats diminished the estrogen-induced increase in the expression of (3-arrestin1. These findings suggest that estrogen enhances the expression of (3-arrestin1 mediated by cFos in the RVLM of OVX rats, thereby alleviating sympathetic nerve hyperactivity and hypertension.
Intrauterine hypoxia is the most frequent adverse intrauterine condition that occurs under a variety of circumstances including preeclampsia, placental insufficiency, high-altitude pregnancy, and any inflammatory condition during pregnancy resulting from gestational diabetes or even maternal obesity. However, early diagnosis of intrauterine hypoxia is still a challenge. In this study, we comparatively analyzed the systolic to diastolic ratio (S/D), resistant index (RI), and pulse index (PI) of the umbilical artery (UmA) and middle cerebral artery (MCA) blood flows obtained from 46 pregnant women with intrauterine hypoxia and 80 normal pregnant women at 28-31, 32-36, and 37-41 gestational weeks. Results found that the S/D, RI, and PI of UmA and MCA blood flows at 28-31, 32-36, and 37-41 gestational weeks were all increased in hypoxic fetuses than in normal fetuses (P<0.05). The malondialdehyde (MDA) level was elevated but superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities were reduced in the UmA blood of pregnant women with intrauterine hypoxia compared with normal pregnant women (P<0.05). It was found that the NADPH oxidase 2 (Nox2) and NADPH oxidase 4 (Nox4) activities were increased in the UmA blood of pregnant women with intrauterine hypoxia compared with normal pregnant women (P<0.05). Results of ELISA methods showed that the expression level of survivin was lower but the expression levels of caspase-3, caspase-6, and caspase-9 were higher in the placental tissues of pregnant women with intrauterine hypoxia than those in normal pregnant women (P<0.05). The concentrations of erythropoietin in the amniotic fluid and UmA blood were increased in pregnant women with intrauterine hypoxia compared with normal pregnant women (P<0.05). The Spearman correlation analysis showed that the S/D, RI, and PI of UmA blood flow at 37-41 gestational weeks were positively correlated with the levels of Nox2, Nox4, and MAD and the UmA concentration of erythropoietin but negatively correlated with the activities of SOD, GSH-Px, and CAT (P<0.05). In summary, the study indicates that ultrasound parameters of the UmA blood flow including S/D, RI, and PI could serve as predictors of intrauterine hypoxia.
Primary ovarian insufficiency (POI) is closely associated with ovarian hormone deficiency, amenorrhea, menopause, and infertility in women. Hormone replacement therapy remains the mainstay of treatment and management of POI. A combined oral contraceptive (Yasmin) containing 0.02 mg ethinylestradiol and 3 mg drospirenone has been shown to be a well-tolerated and effective combination that provides high contraceptive reliability and good cycle control. Herein, we aim to examine clinical efficacy of ethinylestradiol/drospirenone in treating patients with POI and its effects on serum hormone levels, body mass, lipid metabolism, and T lymphocyte subsets. Retrospective analysis of clinical records and follow-up data from 80 patients with POI was performed. The control group contained 40 patients with POI receiving oral administration of 0.035 mg ethinylestradiol and 2 mg cyproterone acetate once a day for consecutive 21 days with drug withdrawal of 7 days in 3 months. The observation group contained 40 patients with POI receiving oral administration of 0.02 mg ethinylestradiol and 3 mg drospirenone once a day for consecutive 28 days in 3 months. There was no significant difference on serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T), concentrations of high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), and triglycerides (TG), body mass, the numbers of CD+3, CD+4, CD+8 T cells, and ratio of CD+4/CD+8 between the control and observation group ( P > 0.05 ) before treatment. After treatment, serum levels of FSH, LH, and T, concentrations of LDL-C, and TG, body mass, and CD+8 T cells were reduced but the concentration of HDL-C, CD+3, and CD+4 T cells and ratio of CD+4/CD+8 were increased in both two groups ( P < 0.05 ); these changes were more significant in the observation group compared with the control group ( P < 0.05 ). Besides, the total response rate of the observation group was 90.00%, which is higher than that of the control group, 77.50% ( P < 0.05 ). The pregnancy rate of the observation group was 45.00%, which is higher than that of the control group, 30.00% ( P < 0.05 ). Taken together, these results suggest that the combined oral contraceptive (Yasmin) containing 0.02 mg ethinylestradiol and 3 mg drospirenone restores hormone levels, improves body mass and lipid metabolism, and sustains autoimmune function for patients with POI, suggesting ethinylestradiol/drospirenone treatment is effective in treating POI.
机器人手术广泛用于妇科肿瘤,可以完成早期宫颈癌、内膜癌、卵巢癌、阴道癌等手术,对于复发的妇科恶性肿瘤的机器人手术治疗报道较少.我们通过相关文献评估机器人手术在妇科恶性肿瘤治疗以及复发手术治疗中的作用.目前认为病灶复发为中央型、孤立病灶者,机器人手术是可行的,手术方式为局部切除和盆腔廓清术,需经验丰富的医生进行;手术方法的改进以及医疗器械的研发也是保证手术成功的重要因素.
In endometrial carcinoma, the clinical outcome directly correlates with the TNM stage, but the lack of sufficient information prevents accurate prediction. The molecular mechanism underlying the competing endogenous RNA (ceRNA) hypothesis has not been investigated in endometrial cancer. Multi-bioinformatic analyses, including differentially expressed gene analysis, ceRNA network construction, Cox regression analysis, function enrichment analysis, and protein-protein network analysis, were performed on the sequence data acquired from The Cancer Genome Atlas (TCGA) data bank. A ceRNA network comprising 366 mRNAs, 27 microRNAs (miRNAs), and 66 long non-coding RNAs (lncRNAs) was established. Survival analysis performed with the univariate Cox regression analysis revealed nine lncRNAs with prognostic power in endometrial carcinoma. In multivariate Cox regression analysis, a signature comprising LINC00491, LINC00483, ADARB2-AS1, and C8orf49 showed remarkable prognostic power. Risk score and neoplasm status, but not TNM stage, were independent prognostic factors of endometrial carcinoma. A ceRNA network comprising differentially expressed mRNAs, miRNAs, and lncRNAs may reveal the molecular events involved in the progression of endometrial carcinoma. In addition, the signature with prognostic value may discriminate patients with increased risk for poor outcome, which may allow physicians to take accurate decisions.
Fuel fine particulate matter (FPM) is an important component of ambient pollution, has wide biological activity, and can cause a variety of diseases. Epidemiological studies have reported that FPM can decrease human fertility rates, retard embryonic growth, cause adverse effects on pregnancy outcomes, and result in male reproductive damage. However, the effects of FPM on female ovary function and associated mechanisms are still unclear. In this research, different concentrations of gasoline and diesel FPM were chosen to treat female mice in vivo. Fuel FPM can significantly inhibit ovarian function and follicle maturation. The hypothalamus-pituitary-ovary axis was inhibited significantly, with an increase in follicle-stimulating hormone and luteinizing hormone levels and a decrease in estradiol levels, as well as ovary weight loss, which was similar to the symptoms of premature ovarian failure in humans. Fuel FPM can induce the accumulation of copper and lead in the ovary and decrease the levels of zinc, magnesium, and manganese. Simultaneously, the steroid biosynthesis signaling pathway was downregulated, which can contribute to ovarian dysfunction. This study provided a new perspective for understanding the ovarian toxicity of fuel FPM and associated mechanisms, which will aid in the development of new methods to treat ovarian dysfunction induced by FPM.
Background: Cervical cancer, one of the leading causes of female deaths, remains a top cause of mortality in gynecologic oncology and tends to affect younger individuals. However, the pathogenesis of cervical cancer is still far from clear. Given the high incidence and mortality of cervical cancer, uncovering the causes and pathogenesis as well as identifying novel biomarkers are of great significance and are desperately needed. Materials and methods: First, raw data were downloaded from the Gene Expression Omnibus database. The Robuse Multi-Array Average algorithm and combat function of the sva package were subsequently applied to preprocess and remove batch effects. Differentially expressed genes (DEGs) analyzed with the limma package were followed by gene ontology and pathway analysis, and a protein-protein interaction (PPI) network based on the STRING website and the Cytoscape software was constructed. Weighted Correlation Network Analysis (WGCNA) was utilized to build the coexpression network. Subsequently, UALCAN websites were employed to conduct survival analysis. Finally, the oncomine database was used to validate the expression of ANLN in other datasets. Results: GSE29570 and GSE89657, including 49 cervical cancer tissues and 20 normal cervical tissues, were screened as the datasets. Three-hundred-twenty-four DEGs were identified and, among them, 123 were upregulated, while 201 were downregulated. The DEGs PPI network complex, contained 305 nodes and 4,962 edges, and 8 clusters were calculated according to k-core = 2. Among them, cluster 1, which had 65 nodes and 1,780 edges, had the highest score in these clusters. In coexpression analysis, there were 86 hubgenes from the Brown modules that were chosen for further analysis. Sixty-one key genes were identified as the intersecting genes of the Brown module of WGCNA and DEGs. In survival analysis, only ANLN was a prognostic factor, and the survival was significantly better in the low-expression ANLN group. Conclusion: Our study suggested that ANLN may be a potential tumor oncogene and could serve as a biomarker for predicting the prognosis of cervical cancer patients.
Objective To explore the clinical factors influencing the prognosis of patients with gestational trophoblastic neoplasia (GTN) after chemotherapy. Methods The clinical data of 55 patients with gestational trophoblastic diseases in our hospital from 2009 to 2016 were retrospectively analyzed, including 26 cases with hydatidiform mole and 29 cases with GTN (23 cases of invasive mole and 6 cases of choriocarcinoma). Among them, 23 GTN patients with the follow-up human chorionic gonadotropin (HCG)<5 U/L for 3 times after chemotherapy were included in this study. The age, reproductive history, lung metastasis, International Federation of Gynecology and Obstetrics (FIGO) stage and other clinical factors which might affect the cure time of GTN patients were analyzed by Cox regression analysis. The relationship between age and reproductive history and cure time were analyzed by Kaplan-Meier survival analysis. Results Cox regression univariate analysis showed that term delivery and abortion were related to the cure time of GTN patients (both P<0.05), and the age was close to statistical significance (P=0.051). Cox multivariate analysis showed that term delivery was an independent factor influencing the cure time of GTN patients (P=0.020). Kaplan-Meier survival analysis showed that age (P=0.043), term delivery (P=0.016) and abortion (P=0.026) were related to the cure time of GTN patients after chemotherapy. Conclusion Older women or women who have histories of term delivery or abortion should be alerted to the occurrence of GTN, which has long cure time and the dynamic changes of blood HCG need to be closely monitored.
Given the high morbidity and the trend of younger individuals being affected observed in cervical cancer, it is important to identify sensitive and effective biomarkers for predicting the survival outcome of patients. Based on data from 307 cervical cancer cases acquired from The Cancer Genome Atlas portal, 1920 differentially expressed mRNAs, 70 microRNAs(miRNAs), and 493 long non-coding(lncRNAs) were screened by comparing cervical cancer tissues with paracancerous tissues. A competing endogenous (ceRNA) network containing 50 lncRNAs, 16 miRNAs, and 81 mRNAs was constructed. Eighteen RNAs, comprising 13 mRNAs, 2 miRNAs, and 3 lncRNAs, were identified as significant prognostic factors by univariate Cox proportional hazards regression. ETS-related gene and fatty acid synthase signatures were discovered using a multivariate Cox regression model built to identify independent prognostic factors in cervical cancer patients. Receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off value for distinguishing the risk level of cervical cancer patients. High-risk patients exhibited a poorer prognosis than low-risk patients did. This study focused on ceRNA networks to provide a novel perspective and insight into cervical cancer and suggested that the identified signature can serve as an independent prognostic biomarker in cervical cancer.
Background: It has been demonstrated that preeclampsia, a pregnancy-specific hypertension disorder, is characterized by high blood pressure (BP) and sympathetic overactivity. Increased reactive oxygen species (ROS) in the rostral ventrolateral medulla (RVLM), a key region for controlling sympathetic tone, has been reported to contribute to high level of BP and sympathetic outflow. The aim of the present study was to determine the role of the RVLM ROS in mediating the preeclampsia-associated cardiovascular dysfunction. Methods: The animal model of preeclampsia was produced by administration of desoxycorticosterone acetate (DOCA) to pregnant rats. Results: Compared with normal pregnant rats without DOCA treatment (NP), the protein concentration and norepinephrine excretion in 24-h urine, as well as BP in pregnant rats with DOCA treatment (PDS) were significantly increased. The levels of superoxide anion and the protein expression of NADPH oxidase subtype (NOX4) in the RVLM were significantly increased in PDS than in NP groups. Furthermore, microinjection of the superoxide dismutase (SOD) mimic Tempol (5 nmol) into the RVLM significantly decreased BP, heart rate, and renal sympathetic never activity in PDS but not in NP group. Conclusion: The present data suggest that high BP and sympathetic overactivity in preeclampsia rats is associated with increased oxidative stress in the RVLM via upregulation of NOX4 expression.