circ-TFRC downregulation suppresses ovarian cancer progression via miR-615-3p/IGF2 axis regulation.

BACKGROUND: Ovarian cancer (OC) is a malignancy among female globally. Circular RNAs (circRNAs) are a family of circular endogenous RNAs generated from selective splicing, which take part in many traits. Former investigation suggested that circ-TFRC was abnormally expressed in breast cancer (BC). Further, the role of circ-TFRC to the progress of OC remains unclear. So, the aim of this study was to reveal the regulatory mechanism of circ-TFRC. METHODS: Our team made the luciferase reporter assay to validate circ-TFRC downstream target. Transwell migration assay, 5-ethynyl-20-deoxyuridine, and cell counting kit-8 were applied to investigate both proliferation and migration. In vivo tumorigenesis and metastasis assays were performed to investigate the circ-TFRC role in OC. RESULTS: The outputs elucidated that circ-TFRC expression incremented in OC cells and tissues. circ-TFRC downregulation inhibited OC cell proliferation as well as migration in in vivo and in vitro experiments. The luciferase results validated that miR-615-3p and IGF2 were circ-TFRC downstream targets. IGF2 overexpression or miR-615-3p inhibition reversed OC cell migration after circ-TFRC silencing. Also, IGF2 overexpression reversed OC cell migration and proliferation post miR-615-3p upregulation. CONCLUSION: Results demonstrate that circ-TFRC downregulation inhibits OC progression and metastasis via IGF2 expression regulation and miR-615-3psponging.

DNA methylation characteristics associated with chemotherapy resistance in epithelial ovarian cancer.

Objective: The high mortality rate of epithelial ovarian cancer (EOC) is often attributed to the frequent development of chemoresistance. DNA methylation is a predictive biomarker for chemoresistance. Methods: This study utilized DNA methylation profiles and relevant information from GEO and TCGA to identify different methylated CpG sites (DMCs) between chemoresistant and chemosensitive patients. Subsequently, we constructed chemoresistance risk models with DMCs. The genes corresponding to candidate DMCs in chemoresistance risk models were further analyzed to identify different methylated gene symbols (DMGs) associated with chemoresistance. The DMGs that showed a strong correlation with the corresponding DMCs were analyzed through immunohistochemistry. Results: Compared to chemosensitive EOC patients, chemoresistant patients showed 423 hypermethylated CpGs and 1445 hypomethylated CpGs. The chemoresistance risk models based on DMCs have shown the improved predictive ability for chemoresistance in EOC (AUC = 65.0-76.2%). The methylations of cg25510164, cg13154880, cg15362155 and cg08665359 were strongly associated with decreased risk of chemoresistance. Conversely, the methylation of cg08872590 and cg14739437 significantly increased the risk. We identified 13 DMGs, from 47 DMCs corresponding genes, between chemosensitive and chemoresistant samples. Among the DMGs, the expression levels of DDR2 and OPCML exhibited strong correlations with the corresponding DMCs. DDR2 and OPCML both showed enhanced expression in chemoresistant ovarian microarray tissue. Conclusions: Hypomethylated CpGs may play a significant role in DNA methylation associated with chemoresistance in EOC. The epigenetic modification of DDR2 could have important implications for the development of chemoresistance. Our study provides valuable insights for future research on DNA methylation in the chemoresistance of EOC.

Association Between Serum Ferritin Levels in Early Pregnancy and Thyroid Function and Pregnancy Outcomes in Chinese Population.

Background: The relationship of iron deficiency and thyroid hormone has been researched a lot among pregnant or other healthy population. However, invisible iron deficiency, namely shortage of serum ferritin (sFer) level, has been barely investigated among Chinese pregnant women. This study aimed to explore the effects of sFer status on thyroid function and pregnancy outcomes in a population-based upper first-class hospital. Methods: A total of 781 singleton pregnant women of gestation in Shanghai General Hospital took part in this retrospective cohort study. The participants were divided into four groups by quartiles of serum ferritin levels (Q1-4). Binary logistic regressions were used to examine the strength of association between the different traits and the serum ferritin (sFer) quartiles separately, where Q1 (lowest ferritin quartile) was taken as the base reference. One-way ANOVA was adopted to compare the averages of the different variables across sFer quartiles. Categorical measures were compared by Fisher exact test or chi-square test. Results: As the sFer concentration rises, incidence of premature birth (15.8%vs 12.3% vs 9.20% vs 6.20% p = 0.016) as well as threatened miscarriage (14.8% vs 7.2% vs 8.70% vs 6.70% p = 0.021) presented a downward trend. Compared with the other sFer group, subjects of the low sFer group were older, more often to be found to have lower serum γT3 and FT4 levels in early pregnancy but not in middle pregnancy. Conclusion: sFer concentration in the first trimester can affect thyroid function. The correction of invisible iron deficiency with inadequate sFer status prior to pregnancy or during early pregnancy is imperative, not only to prevent anemia, but also for maintaining optimum thyroid function and normal fetal development. For clinicians, sFer status of pregnant women should be attached great importance apart from attention to iron level.

Association of gestational hypertriglyceridemia, diabetes with serum ferritin levels in early pregnancy: a retrospective cohort study.

Aims: Previous studies showed conflicting results linking body iron stores to the risk of gestational diabetes mellitus (GDM) and dyslipidemia. We aim to investigate the relationship between serum ferritin, and the prevalence of GDM, insulin resistance (IR) and hypertriglyceridemia. Methods: A total of 781 singleton pregnant women of gestation in Shanghai General Hospital took part in the retrospective cohort study conducted. The participants were divided into four groups by quartiles of serum ferritin levels (Q1-4). Binary logistic regressions were used to examine the strength of association between the different traits and the serum ferritin (sFer) quartiles separately, where Q1 (lowest ferritin quartile) was taken as the base reference. One-way ANOVA was adopted to compare the averages of the different variables across Sfer quartiles. Results: Compared with the lowest serum ferritin quartile (Q1), the ORs for Q3, and Q4 in our population were 1.79 (1.01-2.646), and 2.07 (1.089-2.562) respectively and this trend persisted even after adjusted for age and pre-BMI. Women with higher serum ferritin quartile including Q3 (OR=2.182, 95%CI=1.729-5.527, P=0.003) and Q4(OR=3.137, 95%CI=3.137-8.523, P<0.01)are prone to develop insulin resistance disorders. No significant difference was observed between sFer concentrations and gestational hypertriglyceridemia(GTG) in the comparison among these 4 groups across logistic regressions but TG was found positively correlated with increased ferritin values in the second trimester. Conclusions: Increased concentrations of plasma ferritin in early pregnancy are significantly and positively associated with insulin resistance and incidence of GDM but not gestational dyslipidemia. Further clinical studies are warranted to determine whether it is necessary to encourage pregnant women to take iron supplement as a part of routine antenatal care.

Serum miRNA-204-5p as a potential non-invasive biomarker for the diagnosis of endometrial cancer with sentinel lymph node mapping.

The lymph node status is one of the most critical prognostic factors used in determining adjuvant treatment in endometrial cancer (EC). Lymphadenectomy is associated significant surgical and postoperative risks. The use of sentinel lymph node mapping (SLNM) has emerged as an alternative method to complete lymphadenectomy in EC. However, there remains controversy surrounding the use of SLNM in high-risk disease and its false-negative rate (3%). The authors previously identified miR-204-5p as a tumor-suppressor miRNA associated with lymph node metastasis in EC tissues. The present study demonstrated that serum miR-204-5p in patients with EC has the potential for use as an early diagnostic biomarker combined with SLNM to assess the lymph node status prior to surgery. The present study also aimed to identify the optimal cut-off value of serum miR-204-5p. The relative expression levels of miR-204-5p were detected using reverse transcription-quantitative PCR in the serum of 52 patients with EC (total SLNM). A total of 20 patients diagnosed with ovarian cysts, 20 patients diagnosed with myoma, and 20 participants diagnosed with endometrial polyps or endometrial hyperplasia were included as the control group. miR-204-5p expression was also detected in lymph node tissues using in situ hybridization. The results revealed that serum miR-204-5p expression was downregulated in patients with EC compared with its expression in patients with benign ovarian cysts, myoma and endometrial hyperplasia/polyps (P<0.01). In accordance with the final pathological evaluation, patients with EC with a positive SLN status had a significantly lower level of miR-204-5p compared with those with a negative SLN status (P<0.01). The area under the ROC curve of miR-204-5p was 0.923, 95% CI (0.847-1.000), and the diagnostic value had a sensitivity of 87.2% and specificity of 80.0%, with an optimal cut-off value of 0.253. On the whole, it was demonstrated that a lower miR-204-5p expression is associated with lymph node metastasis in these SLN(+) EC tissues, indicating that the downregulation of serum miR-204-5p in patients with EC has potential for use as an early diagnostic biomarker combined with SLNM. In addition, with a cut-off value of 0.253, it appeared optimal for the prediction of lymph node metastasis in EC.

Influence of painless delivery on the maternal and neonatal outcomes under the guidance of new concept of labor.

OBJECTIVE: To explore the possible influence of painless delivery on the maternal and neonatal outcomes under the guidance of new concept of labor. METHODS: Primiparas who received painless delivery in our hospital were selected for this retrospective clinical study. They were divided into two groups, the experimental group and the control group. The experimental group received painless delivery with the application of new labor management, while the control group received painless delivery with the application of routine labor management. The maternal and neonatal outcomes (postpartum hemorrhage, postpartum urinary retention, fetal distress and neonatal asphyxia), the duration of first and second stages of labor, the total duration of labor, medical intervention during first stage of labor such as artificial rupture of membranes or the use of oxytocin, visual analog scale (VAS) scores upon complete cervical dilation, delivery method and maternal satisfaction rate were compared between the two groups. RESULTS: Among the 208 primiparas, 112 cases were enrolled in the control group and 96 cases in the experimental group. There were no significant differences in the incidences of postpartum hemorrhage, postpartum urinary retention, fetal distress and neonatal asphyxia between the two groups (all P>0.05). The duration of first and second stages of labor and the total duration of labor in the control group were shorter than those in the experimental group (all P<0.001). The rates of artificial rupture of membranes and intravenous use of oxytocin in the control group were higher than those in the experimental group (both P<0.05). The VAS scores upon complete cervical dilation in the control group were significantly higher than those in the experimental group (P<0.05). The vaginal delivery and maternal satisfaction rates were significantly lower in the control group than in the experimental group (both P<0.05). CONCLUSION: Painless delivery under the guidance of new concept of labor has no significant influence on the maternal and neonatal outcomes. Instead, it can prolong the labor process, provide more delivery time for pregnant women, reduce the intervention measures during delivery, decrease the delivery pain and finally increase the natural delivery rate and their satisfaction with delivery, which is worth wide promotion in clinical practice.

Older Underweight Pregnant Women Beat Young Overweight/Obese Ones on Incidence of Gestational Diabetes.

OBJECTIVE: This study aimed to compare the incidence of gestational diabetes mellitus (GDM) in older underweight pregnant women vs young overweight/obese ones. METHODS: A multiracial retrospective-cohort study was conducted in five hospitals of Shanghai on 7,485 women who had been pregnant during 2018-2020. Incidence of GDM was equal to the proportion of GDM cases in the total number of cases observed in the same period. Comparison of GDM incidence of older underweight pregnant women and young overweight/obese ones was done with χ2 tests. ORs and 95% CIs for GDM were estimated using univariate and multivariate logistic regression across gestation age and prepregnancy BMI. RESULTS: Advanced age (OR 1.09, 95% CI 1.072-1.11; P=0) and higher BMI (OR 1.57, 95% CI 1.112-2.212; P=0.01) were found to be risk factors of GDM. The incidence of 13.33% of older underweight pregnant women (age ≥35years, BMI <18.5 kg/m2) developing GDM was lower than that of young overweight/obese ones (age ≤24 years, BMI ≥24 kg/m2). For those aged ≥35years, it is advised that BMI be kept to <18.5 kg/m2. For those aged ≤24 years, BMI control should not exceed 24 kg/m2. CONCLUSION: Older underweight (age≥35years, BMI <18.5 kg/m2) pregnant women beat young overweight/obese ones (age ≤24 years, BMI ≥24 kg/m2) on incidence of GDM. Factors influencing obesity/overweight in GDM were high maternal age, though being young is a promising protective factor for GDM and tolerance of BMI is promoted, but should be limited to certain ranges. Being older increased the chances of developing GDM, but those with lower BMI still had lower GDM incidence than younger pregnant women.

Opportunities for Prevention of Gestational Diabetes Before 24 Weeks of Gestation.

BACKGROUND: Gestational diabetes (GDM), increasingly prevalent worldwide, is related to growing pregnancy complications and long-term metabolic risks for the woman and the descendants. The aim of this study is to determine the optimal BMI ranges specific for age group and optimal gestational weight gain (GWG) at 24 weeks specific for different pre-BMI (pre-pregnancy body mass index) groups to avoid or reduce the incidence of GDM. METHODS: A retrospective cohort study of 3104 pregnant women was conducted in Song Jiang district, Shanghai, China. A multivariate logistic regression analysis was performed with the purpose of determining the OR (odds ratio) of risk factors of GDM including GWG of 24 weeks, pre-BMI, advanced age, and first-degree relatives with DM. Optimal ranges of GWG or pre-BMI are defined as the interval corresponding to lowest or relative lower incidence of GDM. RESULTS: ORs of pre-BMI, maternal age, GWG at 24 weeks, and first-degree relatives with DM were 1.250, 1.096, 1.142, and 2,098 separately. It is suggested for lowering the incidence of GDM that, to the utmost extent, 12 kg, 9 kg, and 8 kg for GWG at 24 weeks should be the ideal boundary for those pregnant women whose BMI was 15-21 kg/m2, 21-23 kg/m2, and 23-25 kg/m2 respectively. Pre-BMI ≤22 kg/m2 would be recommended for an expectant mother whose age is no more than 28 years old. Similarly, women whose age was above 28 years old would be advised to control their BMI below 20 kg/m2. CONCLUSION: Optimal GWG during pregnancy varies largely by diverse pre-BMI, and likewise, optimal pre-BMI varies a lot by different age group. Public health awareness should be promoted on the importance of having healthy pre-BMI, and achieving optimal weight gain during pregnancy to avoid or reduce the incidence of GDM, especially for those with first-degree relatives with DM.

Automated labeling of the airway tree in terms of lobes based on deep learning of bifurcation point detection.

This paper presents an automatic lobe-based labeling of airway tree method, which can detect the bifurcation points for reconstructing and labeling the airway tree from a computed tomography image. A deep learning-based network structure is designed to identify the four key bifurcation points. Then, based on the detected bifurcation points, the entire airway tree is reconstructed by a new region-growing method. Finally, with the basic airway tree anatomy and topology knowledge, individual branches of the airway tree are classified into different categories in terms of pulmonary lobes. There are several advantages in our method such as the detection of the bifurcation points does not depend on the segmentation of airway tree and only four bifurcation points need to be manually labeled for each sample to prepare the training dataset. The segmentation of airway tree is guided by the detected points, which overcomes the difficulty of manual seed selection of conventional region-growing algorithm. In addition, the bifurcation points can help analyze the tree structure, which provides a basis for effective airway tree labeling. Experimental results show that our method is fast, stable, and the accuracy of our method is 97.85%, which is higher than that of the traditional skeleton-based method. Graphical Abstract The pipeline of our proposed lobe-based airway tree labeling method. Given a raw CT volume, a neural network structure is designed to predict major bifurcation points of airway tree. Based on the detected points, airway tree is reconstructed and labeled in terms of lobes.

Identifying Involvement of H19-miR-675-3p-IGF1R and H19-miR-200a-PDCD4 in Treating Pulmonary Hypertension with Melatonin.

Non-coding RNAs play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). The aim of this study was to characterize the therapeutic role of melatonin as well as the underlying molecular mechanism (its effects on the expression of H19 and its downstream signaling pathways) in the treatment of PAH. Real-time PCR and western blot analysis were performed to evaluate the expression of H19, miR-200a, miR-675, insulin-like growth factor-1 receptor (IGF1R), and programmed cell death 4 (PDCD4). The value of systolic pulmonary artery pressure (SPAP) and the ratio of medial thickening in the monocrotaline (MCT) group were increased, whereas the melatonin treatment could decrease these values to some extent. The weights of RV (right ventricle), LV (left ventricle) + IVS (interventricular septal), and RV/(LV + IVS) in the MCT group were much higher than those in the MCT + melatonin and control groups. In addition, the expression of H19, miR-675, IGF1R mRNA, and IGF1R protein in the MCT group was the highest, whereas their expression in the control group was the lowest. The expression of miR-200, PDCD4 mRNA, and PDCD4 protein in the MCT group was the lowest, whereas their expression in the control group was the highest. Furthermore, H19 directly suppressed the expression of miR-200a, whereas miR-675-3p and miR-200a directly inhibited the expression of IGF1R and PDCD4, respectively. Finally, melatonin treatment inhibited cell proliferation; upregulated the expression of H19, miR-675-3p, and PDCD4; and downregulated the expression of miR-200a and IGF1R. This study demonstrated the role of H19-miR-675-3p-IGF1R- and H19-miR-200a-PDCD4-signaling pathways in the melatonin treatment of PAH.

Pulmonary actinomycosis diagnosed by transbronchoscopic lung biopsy: A case report and literature review.

Pulmonary actinomycosis is a chronic, suppurative, granulomatous disease caused by Actinomyces israelii, an obligate anaerobe. The clinical manifestations and imaging characteristics of pulmonary actinomycosis lack specificity and can lead to confusion with tuberculosis and lung cancer. The present study reported a case of pulmonary actinomycosis diagnosed by transbronchoscopic lung biopsy and reviewed the literature on the disease. The clinical characteristics, signs, laboratory findings as well as progression, diagnosis and treatment in the case of pulmonary actinomycosis were analyzed. The patient was diagnosed by transbronchoscopic lung biopsy. After two weeks of antibiotic therapy, the cough was significantly improved and the patient's temperature returned to normal. Moreover, the lesion in the left lower lung was significantly smaller. Pulmonary actinomycosis is usually confused for tuberculosis and lung cancer. The present findings indicated that transbronchoscopic lung biopsy is a useful tool for diagnosing the disease. To conclude, doctors should have a clear enough understanding of the disease to prescribe empirical antibiotics and avoid unnecessary surgery.

Combined Effects of PVT1 and MiR-146a Single Nucleotide Polymorphism on the Lung Function of Smokers with Chronic Obstructive Pulmonary Disease.

Non-coding RNAs play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). This study was performed to investigate the role of PVT1 and miR-146a single nucleotide polymorphisms (SNPs) in the lung function of COPD smokers. Real-time PCR and Western blot analyses were performed to measure the expression of miR-146 and PVT1 SNPs and determine the effect of these SNPs on the pathogenesis of COPD. A total of 100 COPD smokers were enrolled in this study and divided into four groups as follows: Rs2910164CC/GC + Rs13281615GG; Rs2910164CC/GC + Rs13281615GA/AA; Rs2910164GG + Rs13281615GG; and Rs2910164GG + Rs13281615GA/AA. No obvious differences in terms of age, sex, and body height and weight were found among the four groups. However, the Rs2910164GG + Rs13281615GA/AA was associated with the highest stage of the Global Initiative for Chronic Obstructive Lung Disease and the highest values of the forced vital capacity, forced expiratory volume, and diffusing capacity of carbon monoxide, while the lowest values of these parameters were observed in the Rs2910164CC/GC + Rs13281615GG group. In addition, the highest and lowest COX2 levels were observed in the Rs2910164GG + Rs13281615GA/AA and Rs2910164CC/GC + Rs13281615GG groups, respectively. PVT1 directly and negatively regulated the miR-146a expression, which in turn directly and negatively regulated COX2 expression. Thus, the combined actions of SNP in PVT1 Rs13281615 and miR-146a Rs2910164 affected the lung function in COPD smokers.