Cryoablation combined with dual immune checkpoint blockade enhances antitumor efficacy in hepatocellular carcinoma model mice.

BACKGROUND: Cryoablation (Cryo) is a minimally invasive treatment for tumors. Cryo can activate the body's immune response, although it is typically weak. The immune response induced by Cryo in hepatocellular carcinoma (HCC) is poorly understood. PD-1 and CTLA-4 monoclonal antibodies are immune checkpoint inhibitors used in immunotherapy for tumors. The combined use of these antibodies with Cryo may enhance the immune effect. METHODS: A Balb/c mouse model of HCC was established and treated with Cryo, immune checkpoint blockade (ICB), or Cryo + ICB (combination therapy). The growth trend of right untreated tumors and survival time of mice were determined. The expression of apoptosis-related proteins was detected by Western blot (WB) assay. The percentages of immune cells and immunosuppressive cells were analyzed by flow cytometry. The numbers of infiltrating T lymphocytes were checked by immunohistochemistry, and the levels of T-cell-associated cytokines were detected by Quantitative real-time Polymerase Chain Reaction (qRT-PCR) assays and Enzyme-Linked Immunosorbent Assays (ELISA) assays. RESULTS: Cryo + ICB inhibited the growth of right untreated tumors, promoted tumor cell apoptosis, and prolonged the survival time of mice. Local T-cell infiltration in right tumor tissues increased after the combination therapy, while the number of immunosuppressive cells was significantly reduced. In addition, the combination therapy may induce the production of multiple Th1-type cytokines but reduce the production of Th2-type cytokines. CONCLUSIONS: Cryo can activate CD8+ and CD4+ T-cell immune responses. Cryo + ICB can relieve the immunosuppressive tumor microenvironment and shift the Th1/Th2 balance toward Th1 dominance, further enhancing the Cryo-induced T-cell immune response and resulting in a stronger antitumor immune response.

Intra- and Interimage Reliability of Inter-Rectus Distance Measurements Determined via Ultrasound Imaging by the Same or Different Testers in Women in the Early Postpartum Period.

OBJECTIVES: No consensus regarding the optimal position and location for the measurement of the inter-rectus distance (IRD) via ultrasound (US) has been reached. By investigating the intra- and interimage reliability of IRD measurements taken in different positions and at different locations within and between testers, this study provides a theoretical basis for the current situation. METHODS: The IRD was measured via US in 46 women at 42-60 days after delivery at the superior margin of the umbilicus and 3 cm above, 5 cm above and 3 cm below the umbilicus while the women were in the supine, crunch and standing positions. In the interimage test, every participant was tested 2 times by Physician X and 1 time by Physician Y; in the intraimage test, the images collected by Physician X during the first test were saved in the machines, and two measurements were performed by Physician X and one measurement was performed by Physician Y. Paired t tests and intraclass correlation coefficients (ICCs) were calculated. RESULTS: Only the first IRD measurements by tester X and tester Y at 3 cm below the umbilicus in the crunch position were significantly different (9.56 ± 6.00 versus 11.00 ± 5.55) (P < .05). All the ICCs were greater than .75, and the intratester ICCs were greater than or equal to the corresponding intertester ICCs. The ICCs at 3 cm below the umbilicus were the smallest in the supine and crunch positions and the largest in the standing position due to the increased frequency of IRD values of 0. The ICCs for the crunch position were greatest according to the intraimage test but smallest according to the interimage test. The interimage ICCs between the two testers in the supine position at the superior margin, 3 cm above, 5 cm above, and 3 cm below the umbilicus were .972, .974, .975, and .956, respectively. CONCLUSIONS: Ultrasound imaging (USI) is a reliable method for measuring the IRD in women in the early postpartum period. The dynamic measurement of the IRD at or above the umbilicus in the supine position by different testers in real time showed the highest reliability.

Initiation and duration of folic acid supplementation in preventing congenital malformations.

BACKGROUND: Folic acid (FA) supplementation is associated with a lower risk of the neural tube and heart defects and is recommended for women of childbearing age. Although there are detailed recommendations, differences in the initiation time and duration of FA supplementation remain poorly studied. METHODS: A multicentre prospective study of 17,713 women was conducted. The incidence of congenital malformations in women taking a recommended dosage (e.g. 0.4 or 0.8 mg/day) of FA was compared with that in women without supplementation. The predicted probability of malformations by the initiation time and duration of FA use was estimated to determine optimal options. RESULTS: Periconceptional FA supplementation was associated with a lower and insignificant risk of congenital malformations (1.59% vs. 2.37%; odds ratio [OR] 0.69; 95% confidence interval [CI]: 0.44-1.08), heart defects (3.8 vs. 8.0 per 1000 infants; OR, 0.47; 0.21-1.02), and neural tube defects (7.0 vs. 11.5 per 10,000 infants; OR, 0.64; 0.08-5.15). FA use after pregnancy provided greater protection against total malformations. Statistically significant associations were found in women who initiated FA supplementation in the first month of gestation (OR, 0.55; 95% CI: 0.33-0.91) and in those who supplemented for 1 to 2 months (OR, 0.59; 95% CI: 0.36-0.98). Similar results were found for heart defects. The optimal initiation time was 1.5 (optimal range: 1.1 to 1.9) months before pregnancy and a duration of 4.0 (3.7 to 4.4) months was reasonable to achieve the lowest risk of congenital malformations. Heart defect prevention required an earlier initiation (2.2 vs. 1.1 months before pregnancy) and a longer duration (4.7 vs. 3.7 months) than the prevention of other malformations. CONCLUSIONS: The timely initiation of FA supplementation for gestation was associated with a decreased risk of congenital malformations, which was mainly attributed to its protection against heart defects. The initiation of FA supplementation 1.5 months before conception with a duration of 4 months is the preferred option for congenital malformation prevention. TRIAL REGISTRATION: Chictr.org.cn identifier: ChiCTR-SOC-17010976.

A novel artificial intelligence model for fetal facial profile marker measurement during the first trimester.

BACKGROUND: To study the validity of an artificial intelligence (AI) model for measuring fetal facial profile markers, and to evaluate the clinical value of the AI model for identifying fetal abnormalities during the first trimester. METHODS: This retrospective study used two-dimensional mid-sagittal fetal profile images taken during singleton pregnancies at 11-13+ 6 weeks of gestation. We measured the facial profile markers, including inferior facial angle (IFA), maxilla-nasion-mandible (MNM) angle, facial-maxillary angle (FMA), frontal space (FS) distance, and profile line (PL) distance using AI and manual measurements. Semantic segmentation and landmark localization were used to develop an AI model to measure the selected markers and evaluate the diagnostic value for fetal abnormalities. The consistency between AI and manual measurements was compared using intraclass correlation coefficients (ICC). The diagnostic value of facial markers measured using the AI model during fetal abnormality screening was evaluated using receiver operating characteristic (ROC) curves. RESULTS: A total of 2372 normal fetuses and 37 with abnormalities were observed, including 18 with trisomy 21, 7 with trisomy 18, and 12 with CLP. Among them, 1872 normal fetuses were used for AI model training and validation, and the remaining 500 normal fetuses and all fetuses with abnormalities were used for clinical testing. The ICCs (95%CI) of the IFA, MNM angle, FMA, FS distance, and PL distance between the AI and manual measurement for the 500 normal fetuses were 0.812 (0.780-0.840), 0.760 (0.720-0.795), 0.766 (0.727-0.800), 0.807 (0.775-0.836), and 0.798 (0.764-0.828), respectively. IFA clinically significantly identified trisomy 21 and trisomy 18, with areas under the ROC curve (AUC) of 0.686 (95%CI, 0.585-0.788) and 0.729 (95%CI, 0.621-0.837), respectively. FMA effectively predicted trisomy 18, with an AUC of 0.904 (95%CI, 0.842-0.966). MNM angle and FS distance exhibited good predictive value in CLP, with AUCs of 0.738 (95%CI, 0.573-0.902) and 0.677 (95%CI, 0.494-0.859), respectively. CONCLUSIONS: The consistency of fetal facial profile marker measurements between the AI and manual measurement was good during the first trimester. The AI model is a convenient and effective tool for the early screen for fetal trisomy 21, trisomy 18, and CLP, which can be generalized to first-trimester scanning (FTS).

Maternal traditional Chinese medicine exposure and risk of congenital malformations: a multicenter prospective cohort study.

INTRODUCTION: The potential teratogenic risk of traditional Chinese medicine (TCM) is of widespread concern; however, related evidence is largely absent in humans. This study aimed to compare the prevalence of congenital malformations between pregnant women with and without TCM exposure. MATERIAL AND METHODS: This was a multicenter prospective cohort study of 17 713 women who participated in a survey on periconceptional TCM exposure. Primary outcome was congenital malformations diagnosed from a survey conducted on the day 42 after delivery. RESULTS: A total of 16 751 pregnant women with 273 congenital malformations were included in the analysis. Fetuses exposed to TCM had an increased risk of congenital malformations compared to those without exposure (odds ratio [OR] 2.10; 95% confidence interval [CI] 1.09-4.02) after controlling for potential confounders. There were significant associations with congenital malformations in women with early pregnant exposure (OR 2.04, 95% CI 1.00-4.20) and for those who received ≥2 TCM formulas (OR 5.84, 95% CI 1.44-23.65). Pre-pregnancy TCM exposure was significantly associated with an increased risk of congenital heart defects (OR 12.69; 95% CI 3.01-53.51). CONCLUSIONS: Periconceptional TCM exposure is associated with an increased risk of congenital malformation. This effect was cumulative and sensitive to periconceptional age. Therefore, TCM deserves more attention and should be used cautiously for pregnant women and those trying to become pregnant.

Clinical value of fetal facial profile markers during the first trimester.

OBJECTIVES: To study the correlations between facial profile markers and crown-lump length (CRL) in a Chinese population, and to evaluate the clinical value of these markers for abnormal fetuses during the first trimester (11 to 13+6 gestational weeks).  METHODS: The facial profile markers were as followings: inferior facial angle (IFA), maxilla-nasion-mandible (MNM) angle, facial maxillary angle (FMA), frontal space (FS) distance and profile line (PL) distance. These markers were measured in facial mid-sagittal section through ViewPoint 6 software. The diagnostic value of these markers for abnormal fetuses was assessed by receiver operating characteristic (ROC) curves. RESULTS: According to the first-trimester scanning (FTS) and follow-up, 31 fetuses were enrolled in the abnormal group, including 14 cases of trisomy 21, 7 cases of trisomy 18, 10 cases with cleft lip and palate (CLP), and 1000 normal fetuses were selected. Among the normal fetuses, the IFA, FS distance and PL distance had negative correlations with CRL. The MNM angle and FMA had positive correlations with CRL. The mean IFA values for fetuses with trisomy 21 and trisomy 18 were 74.11° (standard deviation (SD) 7.48) and 69.88° (SD 7.08), respectively, which were significantly smaller than the normal fetuses (p = 0.013; p = 0.003). The mean MNM angle of fetuses with trisomy 18 and CLP were 6.98° (SD 2.61) and 9.41° (SD 2.57), respectively, which were significantly greater than the normal fetuses (p = 0.005; p < 0.001). The mean FMA values of trisomy 18 fetuses were 63.95° (SD 4.77), which was significantly smaller than the normal fetuses (p < 0.001). The mean FS distance of CLP fetuses was -0.22 mm (SD 1.38), which was significantly smaller than the normal fetuses (p < 0.001). The mean PL distance of trisomy 21, trisomy 18 and CLP fetuses were 2.89 mm (SD 0.41), 2.91 mm (SD 0.56) and 2.71 mm (SD 0.37), respectively. The difference with the normal fetuses had no statistical significance (p = 0.56; p = 0.607; p = 0.54). CONCLUSIONS: Fetal facial profile markers had excellent correlations with CRL during the first trimester. IFA had certain clinical significance in detecting trisomy 21. FMA, IFA and MNM angle were reliable indicators for screening trisomy 18. The abnormal MNM angle and FS distance could be used as sensitive indicators for CLP. However, PL distance was not the best markers for trisomy 21, trisomy 18 and CLP.

Ultrasonographic study of fetal facial profile markers during the first trimester.

BACKGROUND: To establish reference ranges of fetal facial profile markers and study their correlations with crown-rump length (CRL) during the first trimester (11 ~ 13+ 6 weeks' gestation) in a Chinese population. METHODS: Ultrasonographic images of measuring fetal nuchal translucency (NT) were retrospectively selected randomly in normal fetuses whose parents were both Chinese. The facial markers included inferior facial angle (IFA), maxilla-nasion-mandible (MNM) angle, facial maxillary angle (FMA) and profile line (PL) distance. These markers were measured through ViewPoint 6 software by two experienced sonographers. RESULTS: Three hundred and eighty fetuses were selected. The ICCs (95 % CI) of intra-operator 1 reproducibility of IFA, MNM angle, FMA, PL distance were 0.944 (0.886 ~ 0.973), 0.804 (0.629 ~ 0.902), 0.834 (0.68 ~ 0.918) and 0.935 (0.868 ~ 0.969), respectively. The ICCs (95 % CI) of intra-operator 2 reproducibility of IFA, MNM angle, FMA, PL distance were 0.931 (0.857 ~ 0.967), 0.809 (0.637 ~ 0.904), 0.786 (0.600 ~ 0.892) and 0.906 (0.813 ~ 0.954), respectively. The ICCs (95 % CI) of inter-operator reproducibility of IFA, MNM angle, FMA, PL distance were 0.885 (0.663 ~ 0.953), 0.829 (0.672 ~ 0.915), 0.77 (0.511 ~ 0.891) and 0.844 (0.68 ~ 0.925), respectively. The average ± SD of IFA, MNM angle, FMA and PL distance were 80.2°±7.25°, 4.17°±1.19°, 75.36°±5.31°, 2.78 ± 0.54 mm, respectively. IFA and PL distance significantly decreased with CRL, while MNM angle and FMA significantly increased with CRL. CONCLUSIONS: It was feasible to measure fetal facial markers during the first trimester. In Chinese population, the reference ranges of IFA, MNM angle, FMA and PL distance were 80.2°±7.25°, 4.17°±1.19°, 75.36°±5.31°, 2.78 ± 0.54 mm, respectively, and the measurements were found to correlate with CRL.

Simultaneous Segmentation of Fetal Hearts and Lungs for Medical Ultrasound Images via an Efficient Multi-scale Model Integrated With Attention Mechanism.

Large scale early scanning of fetuses via ultrasound imaging is widely used to alleviate the morbidity or mortality caused by congenital anomalies in fetal hearts and lungs. To reduce the intensive cost during manual recognition of organ regions, many automatic segmentation methods have been proposed. However, the existing methods still encounter multi-scale problem at a larger range of receptive fields of organs in images, resolution problem of segmentation mask, and interference problem of task-irrelevant features, obscuring the attainment of accurate segmentations. To achieve semantic segmentation with functions of (1) extracting multi-scale features from images, (2) compensating information of high resolution, and (3) eliminating the task-irrelevant features, we propose a multi-scale model with skip connection framework and attention mechanism integrated. The multi-scale feature extraction modules are incorporated with additive attention gate units for irrelevant feature elimination, through a U-Net framework with skip connections for information compensation. The performance of fetal heart and lung segmentation indicates the superiority of our method over the existing deep learning based approaches. Our method also shows competitive performance stability during the task of semantic segmentations, showing a promising contribution on ultrasound based prognosis of congenital anomaly in the early intervention, and alleviating the negative effects caused by congenital anomaly.

The application of three-dimensional ultrasound with reformatting technique in the diagnosis of fetal cleft lip/palate.

OBJECTIVE: To evaluate the clinical value of three-dimensional ultrasound (3D-US) with reformatting technique in the diagnosis of fetal cleft lip/palate (CL/P), especially those involving the secondary palate. METHODS: A total of 113 fetuses suspected with cleft lip (CL) on two-dimensional ultrasound (2D-US) were further evaluated by 2D-US and 3D-US with reformatting technique, in order to clarify the type of oral cleft. Lesions were classified as cleft lip (CL), cleft lip and alveolus (CLA), and cleft lip and palate (CLP) (including primary and secondary palate). All fetuses were followed until birth or termination of pregnancy. The diagnostic accuracies of 2D-US and 3D-US with reformatting technology were compared. RESULTS: Both 2D-US and 3D-US with reformatting successfully detected CLs in the final 103 participants. Among these, 29, 25, and 49 cases were confirmed to have CL, CLA, and CLP, respectively. CL, CLA, and CLP were diagnosed by 2D-US in 34, 66, and 3 cases, respectively, and by 3D-US with reformatting technology in 31, 27, and 45 cases, respectively. The sensitivities of 2D-US and 3D-US with reformatting technology in the diagnosis of CLA were 80% (20/25) and 92.0% (23/25), respectively, and the difference was not statistically significant. For CLP, however, the sensitivities were 6.1% (3/49) and 91.8% (45/49), respectively (P < .001). CONCLUSIONS: Both 2D-US and 3D-US with reformatting technique have high diagnostic accuracy for CL and CLA. However, 3D-US has a much higher diagnostic accuracy for CLP.

lncRNA RPL34-AS1 inhibits cell proliferation and invasion while promoting apoptosis by competitively binding miR-3663-3p/RGS4 in papillary thyroid cancer.

Papillary thyroid cancer (PTC) accounts for 80% of all thyroid cancers and seriously impacts the quality of people's lives. Long noncoding RNAs (lncRNAs) play an important role in PTC. In previous studies, thousands of lncRNAs were screened to study their potential relationships with PTC. The aim of this study was to investigate the effect of RPL34-AS1 in PTC and to explore its potential mechanisms. Bioinformatic analyses were performed to characterize the possible function and biological features of RPL34-AS1. Apoptosis, proliferation, and invasion were detected to assess the effect of RPL34-AS1. Cell proliferation was measured using a Cell Counting Kit-8 assay. Western blot analysis was used to assess the apoptosis proteins Bax and Bcl-2. Cell invasion was measured using a Transwell assay. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to examine RPL34-AS1, miR-3663-3P, and RGS4 expression. Dual-luciferase assay was performed to assess the binding of miR-3663-3P by RPL34-AS1. RIP experiment was used to verify the combination between miR-3663-3p and RGS4. We found that overexpression of RPL34-AS1 could inhibit proliferation and invasion while promoting apoptosis in PTC cell lines. Moreover, RPL34-AS1 could also competitively bind miR-3663-3p and exert its function by regulating the miR-3663-3p/RGS4 in PTC cell lines. We found a previously uncharacterized lncRNA, RPL34-AS1, and studied its function and mechanism in PTC. Our research will provide new insights into PTC and new clues for its clinical treatment.

Sonographic diagnosis and prognosis of fetal arachnoid cysts.

PURPOSE: To explore the clinical significance of sonographic (US) diagnosis of fetal arachnoid cysts and to evaluate their prognosis. METHODS: Sixty fetuses deemed to have arachnoid cysts by prenatal US were included in this study. Data from serial US, prenatal and/or postnatal MRI, or post-mortem examinations were retrospectively analyzed. For live births, the developmental quotient scores were determined using the Gesell Developmental Scale. RESULTS: Thirty fetuses were diagnosed during the second trimester and another 30 fetuses were diagnosed in the third trimester. Fifty-one lesions were located in the supratentorial compartment, and 9 were located in the posterior fossa. Twenty-four lesions were isolated, and the remaining lesions were associated with intracranial and/or extra central nervous system malformations. The evolution of the cysts included progression, stability, or spontaneous resolution. The outcomes included induced abortion, intrauterine death, live birth with either normal neurodevelopment or mental retardation, and infant mortality. Two cases were lost to follow-up. The accuracy of prenatal US diagnosis was 86.2% (50/58). CONCLUSION: Prenatal US is the modality of choice for the diagnosis of fetal arachnoid cysts. Serial US examinations are critical to monitor the lesions. Moreover, prenatal MRI is a valuable complementary tool. For live births, the prognosis appears to be good.

Effect of assisted reproductive technology on fetal brain development assessed by prenatal ultrasonography.

AIMS: The aim was to evaluate whether assisted reproductive technology (ART) affects the development of the fetal central nervous system (CNS). METHODS: This study was carried out on women with singleton pregnancies, including 427 women who became pregnant by ART and 32,859 women with natural conceptions (NCs). The cavum septum pellucidum (CSP) width, transverse cerebellar diameter (TCD), cisterna magna (CM) depth, and lateral ventricle width were measured by ultrasound for 72 normal ART fetuses and 201 normal NC fetuses. The malformation rate of CNS was determined for both groups. RESULTS: In both groups, significant positive correlations with gestational age were found for CSP width (ART: r=0.7841, NC: r=0.7864; P<0.0001) and for TCD (ART: r=0.7698, NC: r=0.6926; P<0.0001). However, neither CM depth nor lateral ventricle width showed a significant correlation with gestational age. None of the measured parameters showed a statistically significant difference between the two groups. The CNS malformation detection rate was 1.2% (5/427) in ART fetuses and 0.9% (296/32,859) in NC fetuses. It did not reach statistical significance (P>0.05). CONCLUSIONS: The development and malformation rate of the fetal CNS is not significantly different between ART and NC fetuses, thus, ART does not affect the development of the fetal brain.

A novel artificial intelligence model for measuring fetal intracranial markers during the first trimester based on two-dimensional ultrasound image.

OBJECTIVE: To establish reference ranges of fetal intracranial markers during the first trimester and develop the first novel artificial intelligence (AI) model to measure key markers automatically. METHODS: This retrospective study used two-dimensional (2D) ultrasound images from 4233 singleton normal fetuses scanned at 11+0-13+6 weeks of gestation at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2018 to July 2022. We analyzed 10 key markers in three important planes of the fetal head. Based on these, reference ranges of 10 fetal intracranial markers were established and an AI model was developed for automated marker measurement. AI and manual measurements were compared to evaluate differences, correlations, consistency, and time consumption based on mean error, Pearson correlation analysis, intraclass correlation coefficients (ICCs), and average measurement time. RESULTS: The results of AI and manual methods had strong consistency and correlation (all ICC values >0.75, all r values >0.75, and all P values <0.001). The average absolute error of both only ranged from 0.124 to 0.178 mm. AI achieved a 100% detection rate for abnormal cases. Additionally, the average measurement time of AI was only 0.49 s, which was more than 65 times faster than the manual measurement method. CONCLUSION: The present study first established the normal standard reference ranges of fetal intracranial markers based on a large Chinese population data set. Furthermore, the proposed AI model demonstrated its capability to measure multiple fetal intracranial markers automatically, serving as a highly effective tool to streamline sonographer tasks and mitigate manual measurement errors, which can be generalized to first-trimester scanning.

Hierarchical online contrastive anomaly detection for fetal arrhythmia diagnosis in ultrasound.

Arrhythmia is a major cardiac abnormality in fetuses. Therefore, early diagnosis of arrhythmia is clinically crucial. Pulsed-wave Doppler ultrasound is a commonly used diagnostic tool for fetal arrhythmia. Its key step for diagnosis involves identifying adjacent measurable cardiac cycles (MCCs). As cardiac activity is complex and the experience of sonographers is often varied, automation can improve user-independence and diagnostic-validity. However, arrhythmias pose several challenges for automation because of complex waveform variations, which can cause major localization bias and missed or false detection of MCCs. Filtering out non-MCC anomalies is difficult because of large intra-class and small inter-class variations between MCCs and non-MCCs caused by agnostic morphological waveform variations. Moreover, rare arrhythmia cases are insufficient for classification algorithms to adequately learn discriminative features. Using only normal cases for training, we propose a novel hierarchical online contrastive anomaly detection (HOCAD) framework for arrhythmia diagnosis during test time. The contribution of this study is three-fold. First, we develop a coarse-to-fine framework inspired by hierarchical diagnostic logic, which can refine localization and avoid missed detection of MCCs. Second, we propose an online learning-based contrastive anomaly detection with two new anomaly scores, which can adaptively filter out non-MCC anomalies on a single image during testing. With these complementary efforts, we precisely determine MCCs for correct measurements and diagnosis. Third, to the best of our knowledge, this is the first reported study investigating intelligent diagnosis of fetal arrhythmia on a large-scale and multi-center ultrasound dataset. Extensive experiments on 3850 cases, including 266 cases covering three typical types of arrhythmias, demonstrate the effectiveness of the proposed framework.

An intelligent quantification system for fetal heart rhythm assessment: A multicenter prospective study.

BACKGROUND: The motion relationship and time intervals of the pulsed-wave Doppler (PWD) spectrum are essential for diagnosing fetal arrhythmia. However, few technologies currently are available to automatically calculate fetal cardiac time intervals (CTIs). OBJECTIVE: The purpose of this study was to develop a fetal heart rhythm intelligent quantification system (HR-IQS) for the automatic extraction of CTIs and establish the normal reference range for fetal CTIs. METHODS: A total of 6498 PWD spectrums of 2630 fetuses over the junction between the left ventricular inflow and outflow tracts were recorded across 14 centers. E, A, and V waves were manually labeled by 3 experienced fetal cardiologists, with 17 CTIs extracted. Five-fold cross-validation was performed for training and testing of the deep learning model. Agreement between the manual and HR-IQS-based values was evaluated using the intraclass correlation coefficient and Spearman's rank correlation coefficient. The Jarque-Bera test was applied to evaluate the normality of CTIs' distributions, and the normal reference range of 17 CTIs was established with quantile regression. Arrhythmia subset was compared with the non-arrhythmia subset using the Mann-Whitney U test. RESULTS: Significant positive correlation (P <.001) and moderate-to-excellent consistency (P <.001) between the manual and HR-IQS automated measurements of CTIs was found. The distribution of CTIs was non-normal (P <.001). The normal range (2.5th to 97.5th percentiles) was successfully established for the 17 CTIs. CONCLUSIONS: Using our HR-IQS is feasible for the automated calculation of CTIs in practice and thus could provide a promising tool for the assessment of fetal rhythm and function.

Fetal umbilical artery thrombosis: prenatal diagnosis, treatment and follow-up.

BACKGROUND: To analyze the ultrasound imaging and clinical characteristics of fetuses with umbilical artery thrombosis (UAT), explore the potential causes of UAT and construct a prognostic prediction model to guide clinical practice. METHODS: This was a retrospective cohort study of fetal UAT cases examined at two academic tertiary referral care centers from 2014 to 2020. The basic information of the participants was obtained by interview during follow-up, and data on clinical treatment, delivery conditions, diagnosis and confirmation were obtained through medical records. Probable causes of thrombosis were explored by comparative analysis of the UAT group to the control group and by further regression analysis. Multivariable logistic regression models were used to evaluate risk factors for adverse pregnancy outcomes. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic value of the prognostic prediction model. RESULTS: Thirty fetuses with UAT were included in this study. UAT occurred mostly in the third trimester of pregnancy, and there was an obvious predominance of right UAT. An abnormal pregnancy history (53.3%) was the most common comorbidity, followed by gestational diabetes mellitus (GDM) (20.0%). GDM and umbilical cord (UC) abnormalities were found to be independent risk factors for the development of UAT. After comprehensive decision-making, over two-thirds of the patients with UAT received urgent treatment, and less than one-third received expectant management. Surprisingly, there were no significant differences in fetal outcomes between the urgent treatment and expectant management groups. Multivariate logistic regression analysis showed that gestational age (GA) at clinical diagnosis and UC abnormalities were independent risk factors for adverse pregnancy outcomes (OR 0.781, p = 0.042; OR 16.779, p = 0.023, respectively). Based on this, we constructed a comprehensive prognostic prediction model. The area under the ROC curve (AUC) was 0.877 (95% CI 0.698-0.970; p < 0.001), which suggested that the combination of GA and UC abnormalities was a better predictor for fetal outcomes in our setting. CONCLUSION: In summary, maternal GDM and fetal UC abnormalities are independent risk factors for UAT. UAT is more frequently observed on the right side. Moreover, poor clinical outcomes for fetuses with UAT are ascribed mainly to GA and UC abnormalities, which should be comprehensively evaluated to choose the appropriate treatment.

Case Report: Candidate Genes Associated With Prenatal Ultrasound Anomalies in a Fetus With Prenatally Detected 1q23.3q31.2 Deletion.

Background: Patients with deletions involving the long arm of chromosome 1 are rare, and the main aim of this study was to refine the genotype-phenotype correlation. Case Report: In this report, a 28-year-old pregnant woman, gravida 2 para 1, at 25+4 weeks of gestation underwent ultrasound examination in our institute. The ultrasonographic findings of the fetus were as follows: (1) fetal growth restriction; (2) cleft lip and palate; (3) bilateral renal hypoplasia; (4) lateral ventriculomegaly; (5) single umbilical artery; (6) absent stomach; (7) coronary sinus dilatation with persistent left superior vena cava, ventricular septal defect and unroofed coronary sinus syndrome. Chromosomal microarray analysis of amniotic fluid from the fetus revealed a 28.025 Mb deletion in 1q23.3q31.2, spanning from position 164,559,675 to 192,584,768 (hg19). Conclusion: Genotype-phenotype correlation might improve prenatal diagnosis of fetuses with chromosome 1q deletion. PBX1 could be a candidate gene for fetal growth restriction, renal hypoplasia and congenital heart disease. Fetal growth restriction was accompanied by decreased renal volume in the fetus. Combined with ultrasonic examination, the application of chromosomal microarray analysis will provide accurate prenatal diagnosis.

Modulation of SERCA2a expression and function by ultrasound-guided myocardial gene transfection.

Sarco/endoplasmic reticulum Ca²+-ATPase (SERCA2a) is important for cardiac physiological function and pathological progression. However, intravenous injection, a commonly applied approach for gene delivery in most studies investigating the expression of SERCA2a in cardiomyocytes, has not been particularly satisfactory. Therefore, in the present study, a modified method was used to transfect this gene into the heart. Specifically, a SERCA2a-knockdown lentivirus was directly injected into the myocardium of adult rats under ultrasound guidance, following which the effectiveness and feasibility of this proposed approach were evaluated. The results demonstrated that compared with traditional intravenous injection, the modified gene delivery method resulted in markedly higher transfection efficiency. In addition, the SERCA2a-knockdown rats exhibited higher rates of arrhythmia and weaker ventricular wall motions compared with those in the control rats, with these symptoms more evident in the rats that received a direct injection into the myocardium compared with those that were intravenously injected. These results suggest that ultrasound-guided injection into the myocardium is an efficient and safe method for gene delivery and for inducing the knockdown of SERCA2a protein expression in cardiomyocytes in their native environment.

Overexpression of lincRNA02471 promote cancer development though miR-758/HIPK3 signaling pathway in papillary thyroid cancer.

AIMS: In previous studies, numerous differential lncRNAs were identified via RNA-sequencing. In this dysregulated lncRNAs, lincRNA02471 attracted our attention due to its highest fold change. The aims of our study mainly focused on the function and mechanism of lincRNA02471 in papillary thyroid cancer. MATERIALS AND METHODS: Overexpression and knockdown vectors were constructed to investigate the function of lincRNA02471. Proliferation, apoptosis, invasion and EMT were performed to assess the function of lincRNA02471. Dual-luciferase reporter assay was performed to explore the relationship between lincRNA02471 and miR-758. RESULTS: We found that lincRNA02471 was manifestly upregulated in papillary cancer tissues. Overexpression of lincRNA02471 significantly promoted the cell proliferation, invasion and inhibited cell apoptosis. Knockdown of lincRNA02471 inhibited the cancer development. We also found that lincRNA02471 negatively regulate miR-758 in papillary thyroid cancer. miR-758 can restore the effect of lincRNA02471. Besides, we identified that HIPK3 was the direct target of miR-758. CONCLUSION: we performed comprehensive study of lincRNA02471 and explore its function and mechanism in papillary thyroid cancer. lincRNA02471 can sponge miR-758 and positively regulate HIPK3 to promote papillary thyroid cancer development. Our study provides new target for clinical treatment and new clues for understanding the molecular mechanism of cancer development.

Ultrasound-guided percutaneous laser ablation for papillary thyroid microcarcinoma: a retrospective analysis of 37 patients.

BACKGROUND: Over the past ten years, more papillary thyroid microcarcinoma (PTMC) has been diagnosed more frequently due to the development of imaging technology, and the incidence of PTMC has increased significantly. Ultrasound-guided percutaneous laser ablation (PLA) is mainly used for benign thyroid nodules, and few studies have been published on the use of PLA for PTMC. In the present study, a retrospective analysis was performed to explore the efficacy of PLA for PTMC. METHODS: A total of 37 patients with PTMC who underwent PLA were included in this study. Measurement of the lesion volume and serum thyroid hormone levels and clinical evaluation were performed at 1, 3, 6, and 12 months and every 6 months thereafter. RESULTS: We found that all patients were successfully treated with PLA without serious complications. At the last follow-up visit, 12/37 (32.4%) primary lesions had disappeared, and 24/37 (64.9%) remained as cicatricial hyperplasia. One patient (2.7%) had cervical lymph node metastasis at 24 months post-operatively and underwent open surgery. CONCLUSION: Our initial studies suggest that ultrasound-guided PLA is a safe and effective treatment for PTMC.