Background Strong and synchronized contractions that occur in the last stage of pregnancy are essential for onset of labor. In clinics, the lack of effective description of these characteristics results in inaccurate prediction of the onset of labor. The commonly used contraction monitoring device tocodynamometer (TOCO) detects contractions with relatively high specificity but is unable to quantify the strength and synchrony. The electrohysterography (EHG) quantifies the myoelectric activities that trigger contractions of muscle cells under the electrodes. Therefore, multiple channel EHG signals are well suited for characterizing the strength and synchrony of uterine contractions via their spatiotemporal pattern. Object: The purpose of this study was to provide quantitative descriptions of the contraction characteristics and to investigate their significance for predicting the spontaneous onset of labor in nulliparous women. Study Design: 100 pregnant women with a gestational age of more than 37 weeks were recruited for the study. Multichannel EHG and tocodynamometer recordings were performed simultaneously for 46 of them, both during pregnancy and during labor (defined a time to onset of labor (TTL) less than 24 h). Contractions were identified from the TOCO recordings, and then the frequency and duration of contractions were determined. The multichannel EHG segments under the identified contractile time windows were used to calculate the strength and level of synchrony. Statistical analyses were carried to demonstrate the difference of these variables between the pregnant and labor groups. Multivariate logistic regression was created to provide obstetricians with an assessment tool in predicting spontaneous onset of term labor. Results The frequency, duration, strength, and level of synchrony of uterine contractions for 46 pregnant women during their 37 weeks of gestation to the onset of labor were quantified. All constructed features in labor, with the exception of concordance correlation-based synchrony \(\:\psi\:\), showed statistically significant differences from those in pregnant phase, with degree of synchrony described by the sample entropy SamEn being the strongest feature for distinguishing pregnant and labor (0.5154 ± 0.1720 vs. 0.3555 ± 0.1422, \(\:p=0.00001\)). The multivariate logistic regression model constructed from these features showed high significance in identifying the onset of spontaneous labor in nulliparous women, with an AUC value of 0.80. Conclusion The contraction properties in terms of frequency, duration, strength, and level of synchrony have been quantitated. Continuous observations on 46 pregnant women throughout their pregnancy demonstrated statistically significant difference between contractions in pregnant and labor phase, which enabled a prediction model on spontaneous onset of labor in term nulliparous women.
Monitoring fetal heart rate (FHR) is essential for the early detection of fetal distress and ensuring safe delivery. Direct invasive fetal electrocardiography (FECG) provides reliable FHR signals but is limited to use during labor. Noninvasive fetal heart monitoring can be achieved through abdominal electrocardiography (AECG), where fetal heartbeat waveforms are captured from electrodes placed on maternal abdomen. However, accurately locating fetal R-peaks and obtaining FHRs remain challenging due to interference from uterine contractions and maternal heartbeats. To address this challenge, we proposed an end-to-end fetal R-peak detection method based on sample point classification. Inspired by semantic segmentation in image analysis, we utilized an encoder-decoder model to classify each point in the 1-D AECG signal. The model captures the global contextual information of fetal heartbeat waveforms by combining convolutional neural networks (CNNs) and transformer, resulting in a high-precision classification of each sample point in the AECG signal. Moreover, to mitigate the impact of misclassified points on fetal R-peak detection, we proposed a postprocessing method based on the periodicity of heartbeats. The effectiveness of the proposed method is validated on two AECG databases, achieving satisfactory results with an average F1-score of 98.91%. These findings demonstrate the potential application of long-term fetal monitoring using portable devices. The code is publicly available at https://github.com/ZJUT-CBS/FR-Net .
Background:Pregnancy luoteomas are tumor-like ovarian lesions that emerge during pregnancy and spontaneously regress after delivery. Antenatal diagnosis is infrequently reported, and unnecessary surgery appears to be common in literature reports. Case summary:A 28-year-old primigravida with bilateral adnexal masses was discovered at 32 + 5 weeks during prenatal ultrasound evaluation. Combined with clinical presentation, auxiliary examinations including blood test, magnetic resonance imaging, gastroscopy, and consultation of multi-disciplinary team, we successfully made a diagnosis of pregnancy luteoma and provided conservative management recommendations. A cesarean section was conducted on this patient at 34 + 2 weeks of gestation due to fetal distress. The newborn was small for gestational age but normal in appearance. We performed biopsies of the adnexal masses, which were confirmed to be pregnancy luteomas using both intraoperative frozen section and final pathological diagnosis. Serum testosterone, cancer antigen 125, and alpha-fetoprotein levels gradually declined and normalized on postoperative day 28. The masses significantly decreased in size as shown by ultrasonic and magnetic resonance imaging examination on postoperative day 7, with the ovaries returning to their normal size by postoperative day 30. Conclusion:Prenatal diagnosis of pregnancy luteoma poses a challenge, requiring hormonal examinations, ultrasound, magnetic resonance imaging, and gastrointestinal endoscopy for identification. Caution must be exercised to avoid overtreatment. While additional cases are needed to summarize the imaging features and effects of excess hormones on the both mother and fetus, further research is necessary for a comprehensive understanding.
Uterine contractions are routinely monitored by tocodynamometer (TOCO) at late stage of pregnancy to predict the onset of labor. However, TOCO reveals no information on the synchrony and coherence of contractions, which are important contributors to a successful delivery. The electrohysterography (EHG) is a recording of the electrical activities that trigger the local muscles to contract. The spatial-temporal information embedded in multiple channel EHG signals make them ideal for characterizing the synchrony and coherence of uterine contraction. To proceed, contractile time-windows are identified from TOCO signals and are then used to segment out the simultaneously recorded EHG signals of different channels. We construct sample entropy SamEn and Concordance Correlation based feature ψ from these EHG segments to quantify the synchrony and coherence of contraction. To test the effectiveness of the proposed method, 122 EHG recordings in the Icelandic EHG database were divided into two groups according to the time difference between the gestational ages at recording and at delivery (TTD). Both SamEn and ψ show clear difference in the two groups (p<10-5) even when measurements were made 120 h before delivery. Receiver operating characteristic curve analysis of these two features gave AUC values of 0.834 and 0.726 for discriminating imminent labor defined with TTD ≤ 24 h. The SamEn was significantly smaller in women (0.1433) of imminent labor group than in women (0.3774) of the pregnancy group. Using an optimal cutoff value of SamEn to identify imminent labor gives sensitivity, specificity, and accuracy as high as 0.909, 0.712 and 0.743, respectively. These results demonstrate superiority in comparing to the existing SOTA methods. This study is the first research work focusing on characterizing the synchrony property of contractions from the electrohysterography signals. Despite the very limited dataset used in the validation process, the promising results open a new direction to the use of electrohysterography in obstetrics.
ObjectiveIn this study, we summarize the clinical characteristics and neonatal outcomes of patients with pregnancy luteomas that were identified incidentally at cesarean section in our hospital. We also provide a review of the existing literature relating to this condition.MethodsA total of seven cases of pregnancy luteoma were enrolled from our hospital into this retrospective study between March 2013 and February 2018. We then evaluated the clinical characteristics and neonatal outcomes of these patients.ResultsAll seven patients with pregnancy luteomas found incidentally during Cesarean sections at term as a result of obstetric indications. These masses were unilateral and ranged from 2 to 10 cm in size. All patients underwent partial ovariectomies or oophorocystectomy due to presumptive benign ovarian tumors. Two patients had gestational diabetes and one patient had gestational hypertension. One patient developed hirsutism and a deepened voice. Of the seven newborns, three were girls and four were boys. Physical examinations of the newborns were normal and no virilization was detected among the infant girls.ConclusionPregnancy luteoma may be more common than expected. Better strategies are now needed to educate obstetricians about the clinical features of pregnancy luteoma so that they can avoid unnecessary surgery.
The aim of this study was to assess the correlation of TWIST1 expression with clinical parameters and the prognosis of type I endometrial cancer (EC). This retrospective study enrolled 345 patients. Immunohistochemical staining was performed on 55 normal endometrium (NE) samples, 27 atypical hyperplasia (AH) samples, and 263 type I EC samples. The association between TWIST1 staining and clinical characteristics and survival was evaluated by univariate and multivariate analyses. We found significantly higher TWIST1 expression in patients with AHs and type I ECs than NEs, but there was no significant difference between TWIST1 expression in AHs and type I ECs. Aberrant TWIST1 expression was significantly associated with clinical parameters, indicating poor prognosis and shorter patient survival. Pearsons Chi-Squared test showed that high TWIST1 expression was significantly associated with a shorter disease-free survival and overall survival. More importantly, multivariate analysis showed that high TWIST1 expression, in addition to myometrial invasion, lymph vascular space invasion, and lymph node metastasis, was an independent predictor of worse DFS in patients with type I ECs. Our findings suggest that TWIST1 might be useful in diagnosing ECs and predicting prognosis in patients with AHs and type I ECs.
Studies have identified a series of lncRNAs that contributed to various tumors, although the underlying mechanisms remain largely unclear. We proposed a ceRNA network and investigate relations among lncRNA/miRNA/mRNA in cervical cancer (CC). The genes of differential expression and lncRNA/miRNA/mRNA network were identified by combining TCGA, miRcode, starBase, miRTarBase, miRDB, TargetScan and STRING databases. Meanwhile, the function enrichment was recognized with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Quantitative real time-PCR (qRT-PCR) was performed to determine colorectal neoplasia differentially expressed (CRNDE) expression in CC tissues and cell lines. The effects of CRNDE on the CC biological functions and cyclin B1 (CCNB1) expression were detected by conducting in vitro and in vivo experiments. Quantitative real time-PCR, western blot and dual-luciferase reporter assay were used to predict the target of miR-183. Furthermore, rescue experiments were conducted to further confirm the regulation of CCNB1 by CRNDE. Systematic analyses of bioinformatics from several databases predicted that CRNDE, miR-183 and CCNB1 were in the same network path. Their expressions were up-regulated in CC tissues and cells. Silencing CRNDE-inhibited cell proliferation, migration and invasion, restricted solid tumor growth and promoted cell apoptosis. Moreover, our results suggested that miR-183 targeted the CCNB1 3'UTR and regulated its expression. Additionally, miR-183 mimic could inverse the antitumor function of CRNDE inhibition and partially eliminated the attenuated expression of CCNB1 induced by silencing CRNDE, indicating that CRNDE could positively regulate CCNB1 expression by sponging miR-183. Our study highlighted a role for the CRNDE/miR-183/CCNB1-axis in CC and offered a promising diagnostic strategy for CC treatment.
Purpose Persistent infection with high-risk human papillomavirus (HR-HPV) is thought to play a prominent role in the initiation and progression of almost all cases of cervical cancer. Previously, we and others found that microRNA 34a (miR-34a) may be regulated by HR-HPV E6 to contribute to the development of cervical cancer. Here, we aimed to identify the oncogenic potential and clinical significance of a known miR-34a target, WNT1, in cervical squamous cell carcinoma (SCC) development and to investigate the associated mechanisms underlying cervical SCC cell proliferation and invasion. Methods WNT1 and miR-34a expression levels were assessed in primary cervical lesions using immunohistochemistry and qRT-PCR, respectively. The cellular effects and the expression of its associated genes were examined in cervical SCC-derived Siha and Caski cells after siRNA-WNT1 (downregulation) or miR-34a mimic (upregulation) treatment. A cervical SCC xenograft mouse model was used to investigate the in vivo effects of miR-34a overexpression. HPV-16 E6/E7 expression was inhibited by gene promoter siRNA targeting, after which the levels of miR-34a and WNT1 were examined. Results WNT1 protein upregulation was found to be associated with a poor prognosis in cervical SCC patients. In vitro assays in Siha and Caski cells revealed that WNT1 downregulation decreased cell proliferation and invasion, inhibited WNT/β-catenin activation and affected the expression of E-cadherin and P-cadherin. MiR-34a upregulation resulted in decreased WNT1 expression. An inverse correlation between miR-34a and WNT1 expression was also observed in primary cervical SCC tissues. In addition, we found that MiR-34a could regulate an E-cadherin to P-cadherin switch (E-P cadherin switch) to inhibit cell proliferation and tumorigenesis in vitro and in vivo via inactivation of the WNT1/β-catenin pathway. Finally, we found that decreased HPV-16 E6/E7 expression resulted in miR-34a upregulation and WNT1 downregulation in Siha and Caski cells. Conclusions From our results we conclude that WNT1, as a target of miR-34a, can promote cervical SCC cell proliferation and invasion by induction of an E-P cadherin switch via the WNT1/β-catenin pathway. Our results may provide new options for the treatment of patients with cervical SCC.
Natural bioactive components are increasingly being applied in cancer research. Alpinetin is a type of natural flavonoid primarily derived from Alpinia katsumadai Hayata, which exhibits anti-bacterial and anti-inflammatory properties. Therefore, it may possess anticancer potential and be employed therapeutically for different diseases. The aim of the present study was to investigate the anticancer effects of alpinetin on the SKOV3 ovarian cancer cell line. The effect of alpinetin treatment on SKOV3 cell proliferation, apoptosis, spheroid and colony formation were measured using Cell Counting kit-8, cell apoptosis, 3D spheroid and colony formation assays, respectively. Analysis of the cell cycle was performed using flow cytometry. Western blot analysis was used to determine the protein expression levels of B-cell lymphoma (Bcl)-2, Bcl-2-associated X protein, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP), cyclin D1, cyclin-dependent kinase (CDK) 4, CDK6, signal transducer and activator of transcription (STAT) 3, phosphorylated (p)-STAT3, c-myc, survivin, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, matrix metalloproteinase (MMP)-2 and MMP-9. In addition, a wound healing assay was used to determine cancer cell migration. The results revealed alpinetin suppressed cell viability and induced apoptosis of SKOV3 cells in a dose- and time-dependent manner, and cells were arrested in the G(1) phase. Alpinetin treatment upregulated protein expression levels of Bax, cleaved caspase-3 and PARP, and downregulated protein expression levels of Bcl-2, cyclin D1, CDK4 and CDK6. Alpinetin also inhibited cell migration, through increased protein expression levels of TIMP-1 and TIMP-2, and decreased protein expression levels of MMP-2 and MMP-9. Alpinetin also significantly suppressed colony and spheroid formation by SKOV3 cells. In addition, the STAT3 pathway was suppressed as demonstrated by downregulation of p-STAT3 and reduced expression of downstream factors, including c-myc and survivin. Overall, these results indicated that alpinetin may have anticancer effects on human ovarian cancer by inhibiting the STAT3 signaling pathway.
Purpose: The aim of this study was to understand and investigate the reproductive outcomes of patients with rudimentary horn pregnancies after surgical removal of the rudimentary horn. Materials and Methods: The clinical records, including age, obstetric history, gestational age (weeks), presenting feature, preoperative diagnosis, intraoperative diagnosis, blood loss, and surgical management of women who were diagnosed with pregnancy in the rudimentary horn from 2006 to 2010 were reviewed in this retrospective study. The reproductive outcomes of these women that underwent surgical removal of the rudimentary horn were also recorded during the two-year follow-up period. Results: Fifteen women diagnosed with rudimentary horn pregnancies were included in this study and non-communicating horn was accounted for 87.3% of these cases. The gestation periods of them varied from six to 26 weeks. Rupture of the uterine wall occurred in three cases (20%) and no maternal deaths were observed. Eleven patients underwent laparotomy for rudimentary horn removal and four underwent laparoscopic removal. During the two-year follow-up period, ten out of 15 patients (66.7%) became pregnant and seven of them delivered babies, whereas two asked for medical abortion, and only one had spontaneous abortion during the first trimester. Among the seven women giving live births, three of them were vaginally delivered and four were by cesarean section, five women were term pregnancy, and the other two women gave birth prematurely. Conclusion: This study indicates