A rare inherited homozygous missense variant in PLA2G6 influences susceptibility to infantile neuroaxonal dystrophy: a case report.

Background: Infantile neuroaxonal dystrophy (INAD) is an ultra-rare early-onset autosomal recessive neurodegenerative disorder due to PLA2G6 variants. The clinical symptoms of INAD patients display considerable diversity, and many PLA2G6 variants are still not thoroughly investigated in relation to their associated clinical presentations. Case Description: A 16-month-old boy was admitted to our hospital due to regression of acquired motor and speech abilities that had persisted for 4 months. The patient was born to a healthy consanguineous couple after 41 weeks of pregnancy and natural delivery. Before 12 months old, he had normal motor development milestones. On admission, he also showed astasia-abasia, weakness of distal muscles, and diminished patellar tendon reflex. Brain magnetic resonance imaging (MRI) revealed cerebellar atrophy. Auditory brainstem response (ABR) indicated moderately severe hearing loss. With chromosome microarray analysis (CMA), we identified several copy number-neutral regions of runs of homozygosity (ROH) in the patient. Whole-exome sequencing (WES) further revealed that the patient harbored a homozygous missense variant NM_003560.2: c.1778C>T, p.Pro593Leu (rs1451486649) in the PLA2G6 gene. In the patient's asymptomatic parents and brother, the PLA2G6 c.1778C>T variant stayed in heterozygous status as confirmed by Sanger sequencing. The patient was finally diagnosed with INAD. Conclusions: We report an INAD child with a rare PLA2G6 c.1778C>T homozygous missense variant and associated clinical symptoms. The family-based cosegregation analysis reveals that the PLA2G6 c.1778C>T homozygous variant contributes to the pathogenesis of INAD.

Loss of keratin 23 enhances growth inhibitory effect of melatonin in gastric cancer.

To investigate the effect of keratin 23 (KRT23) on the anticancer activity of melatonin (MLT) against gastric cancer (GC) cells, microarray analysis was applied to screen differentially expressed genes in AGS GC cells following MLT treatment. Western blotting was used to detect the expression of KRT23 in GC cells and normal gastric epithelial cell line GES­1. KRT23 knockout was achieved by CRISPR/Cas9. Assays of cell viability, colony formation, cell cycle, electric cell­substrate impedance sensing and western blotting were conducted to reveal the biological functions of KRT23­knockout cells without or with MLT treatment. Genes downregulated by MLT were enriched in purine metabolism, pyrimidine metabolism, genetic information processing and cell cycle pathway. Expression levels of KRT23 were downregulated by MLT treatment. Expression levels of KRT23 in AGS and SNU­216 GC cell lines were significantly higher compared with normal gastric epithelial cell line GES­1. KRT23 knockout led to reduced phosphorylation of ERK1/2 and p38, arrest of the cell cycle and inhibition of GC cell proliferation. Moreover, KRT23 knockout further enhanced the inhibitory activity of MLT on the tumor cell proliferation by inhibiting the phosphorylation of p38/ERK. KRT23 knockout contributes to the antitumor effects of MLT in GC via suppressing p38/ERK phosphorylation. In the future, KRT23 might be a potential prognostic biomarker and a novel molecular target for GC.

Deep learning system improved detection efficacy of fetal intracranial malformations in a randomized controlled trial.

Congenital malformations of the central nervous system are among the most common major congenital malformations. Deep learning systems have come to the fore in prenatal diagnosis of congenital malformation, but the impact of deep learning-assisted detection of congenital intracranial malformations from fetal neurosonographic images has not been evaluated. Here we report a three-way crossover, randomized control trial (Trial Registration: ChiCTR2100048233) that assesses the efficacy of a deep learning system, the Prenatal Ultrasound Diagnosis Artificial Intelligence Conduct System (PAICS), in assisting fetal intracranial malformation detection. A total of 709 fetal neurosonographic images/videos are read interactively by 36 sonologists of different expertise levels in three reading modes: unassisted mode (without PAICS assistance), concurrent mode (using PAICS at the beginning of the assessment) and second mode (using PAICS after a fully unaided interpretation). Aided by PAICS, the average accuracy of the unassisted mode (73%) is increased by the concurrent mode (80%; P < 0.001) and the second mode (82%; P < 0.001). Correspondingly, the AUC is increased from 0.85 to 0.89 and to 0.90, respectively (P < 0.001 for all). The median read time per data is slightly increased in concurrent mode but substantially prolonged in the second mode, from 6 s to 7 s and to 11 s (P < 0.001 for all). In conclusion, PAICS in both concurrent and second modes has the potential to improve sonologists' performance in detecting fetal intracranial malformations from neurosonographic data. PAICS is more efficient when used concurrently for all readers.

One case of congenital myopathy caused by new mutation of RYR1 gene and literature review.

OBJECTIVE: To report a case of congenital myopathy caused by RYR1 gene complex heterozygous mutation and analyze the pathogenicity of the mutation. Method The clinical manifestation, laboratory examination, imaging findings, muscle pathology and gene test results of a child with congenital myopathy were analyzed retrospectively. Combined with literature review, it is analyzed and discussed. Result The child, female, was admitted to hospital because of "dyspnea for 22 min after asphyxia resuscitation". The main manifestations are low muscle tension, the original reflex cannot be drawn out, the trunk and proximal muscles are weak, and the tendon reflex is not drawn out. The pathological signs were negative. The electrolyte of blood liver and kidney function, blood thyroid and blood ammonia were not abnormal, and creatine kinase increased temporarily. Electromyography suggests myogenic damage. Whole exome sequencing showed that there was a new compound heterozygous variation in RYR1 gene c.14427_ 14429del/c.14138C＞T.Western blot showed that the expression of RYR1 protein in patients was significantly lower than that in normal controls. Conclusion The compound heterozygous variation of RYR1 gene c.14427 was reported for the first time in China_ 14429del/c.14138c > t is the pathogenic gene of the child. The new discovery of RYR1 gene spectrum was revealed, which expanded the RYR1 gene spectrum.

Comparison of performance between O-RADS, IOTA simple rules risk assessment and ADNEX model in the discrimination of ovarian Brenner tumors.

PURPOSE: To describe the clinical and sonographic features of ovarian benign Brenner tumor (BBT) and malignant Brenner tumor (MBT), and to compare performance of four diagnostic models in differentiating them. METHODS: Fifteen patients with BBTs and nine patients with MBTs were retrospectively identified in our institution from January 2003 and December 2021. One ultrasound examiner categorized each mass according to ovarian-adnexal reporting and data system (O-RADS), international ovarian tumor analysis (IOTA) Simple Rules Risk (SR-Risk) assessment and assessment of different neoplasias in the adnexa (ADNEX) models with/without CA125. Receiver operating characteristic curves were generated to compare diagnostic performance. RESULTS: Patients with MBT had higher CA125 serum level (62.5% vs. 6.7%, P = 0.009) and larger maximum diameter of lesion (89 mm vs. 43 mm, P = 0.009) than did those with BBT. BBT tended to have higher prevalence of calcifications (100% vs. 55.6%, P = 0.012) and acoustic shadowing (93.3% vs. 33.3%, P = 0.004), and lower color scores manifesting none or minimal flow (100.0% vs. 22.2%, P < 0.001). Areas under curves of O-RADS, IOTA SR-Risk and ADNEX models with/without CA125 were 0.896, 0.913, 0.892 and 0.896, respectively. There were no significant differences between them. CONCLUSION: BBTs are often small solid tumors with sparse color Doppler signals, which contain calcifications with posterior acoustic shadowing. The most common pattern of MBT is a large multilocular-solid or solid mass with irregular tumor borders, and most were moderately or richly vascularized at color Doppler. These four models have excellent performance in distinguishing them.

[Clinical and genetic analysis of a fetus with 17q12 microdeletion syndrome].

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a fetus with 17q12 microdeletion syndrome. METHODS: A fetus with 17q12 microdeletion syndrome who was diagnosed at Huzhou Maternal & Child Health Care Hospital in June 2020 was selected as the study subject. Clinical data of the fetus was collected. The fetus was subjected to chromosomal karyotyping and chromosomal microarray analysis (CMA). To determine the origin of fetal chromosomal abnormality, its parents were also subjected to CMA assay. The postnatal phenotype of the fetus was also investigated. RESULTS: Prenatal ultrasound revealed polyhydramnios and fetal renal dysplasia. The fetus was found to have a normal chromosomal karyotype. CMA has detected a 1.9 Mb deletion in the 17q12 region, which has encompassed five OMIM genes including HNF1B, ACACA, ZNHIT3, CCL3L1 and PIGW. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the 17q12 microdeletion was predicted as pathogenic copy number variation (CNV). CMA analysis has detected no pathogenic CNV in both parents. After birth, the child was found to have renal cysts and abnormal brain structure. Combined with the prenatal findings, the child was diagnosed with 17q12 microdeletion syndrome. CONCLUSION: The fetus has 17q12 microdeletion syndrome presenting as abnormalities of the kidney and central nervous system, which are strongly correlated with functional defects of the deletion region involving the HNF1B and other pathogenic genes.

Ad5-nCoV booster and Omicron variant breakthrough infection following two doses of inactivated vaccine elicit comparable antibody levels against Omicron variants.

Little information is available for antibody levels against SARS-CoV-2 variants of concern induced by Omicron breakthrough infection and a third booster with an inactivated vaccine (InV) or Ad5-nCoV in people with completion of two InV doses. Plasma was collected from InV pre-vaccinated Omicron-infected patients (OIPs), unvaccinated OIPs between 0 and 22 days, and healthy donors (HDs) 14 days or 6 months after the second doses of an InV and 14 days after a homogenous booster or heterologous booster of Ad5-nCoV. Anti-Wuhan-, Anti-Delta-, and Anti-Omicron-receptor binding domain (RBD)-IgG titers were detected using enzyme-linked immunosorbent assay. InV pre-vaccinated OIPs had higher anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers compared to unvaccinated OIPs. Anti-Wuhan-RBD-IgG titers sharply increased in InV pre-vaccinated OIPs 0-5 days postinfection (DPI), while the geometric mean titers (GMTs) of anti-Delta- and anti-Omicron-RBD-IgG were 3.3-fold and 12.0-fold lower. Then, the GMT of anti-Delta- and anti-Omicron-RBD-IgG increased to 35 112 and 28 186 during 11-22 DPI, about 2.6-fold and 3.2-fold lower, respectively, than the anti-Wuhan-RBD-IgG titer. The anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers declined over time in HDs after two doses of an InV, with 25.2-fold, 5.6-fold, and 4.5-fold declination, respectively, at 6 months relative to the titers at 14 days after the second vaccination. Anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers elicited by a heterologous Ad5-nCoV booster were significantly higher than those elicited by an InV booster, comparable to those in InV pre-vaccinated OIPs. InV and Ad5-nCoV boosters could improve humoral immunity against Omicron variants. Of these, the Ad5-nCoV booster is a better alternative.

Lonicerae Japonicae Flos Attenuates Neutrophilic Inflammation by Inhibiting Oxidative Stress.

Lonicerae japonicae flos (LJ) is an Asian traditional herb that is used as a dietary supplement, tea, and beverage to clear heat and quench thirst. However, no studies investigated its effect on activated human neutrophils, which played a crucial role in the bad prognosis of coronavirus disease of 2019 (COVID-19) patients by aggravating lung inflammation and respiratory failure. Herein, we evaluated the anti-inflammatory effect of LJ ethanol extract (LJEE) on human neutrophils activated by N-formyl-methionyl-leucyl-phenylalanine (fMLF). Our experimental results indicated that LJEE suppressed fMLF-activated superoxide anion (O2•-) generation, the expression of CD11b, and cell adhesion and migration, as well as the formation of neutrophil extracellular traps in human neutrophils. Further in-depth mechanical investigation revealed that pretreatment with LJEE accelerated the Ca2+ clearance, but did not affect the phosphorylation of mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt) in activated human neutrophils. In addition, LJEE displayed a dose-dependent reactive oxygen species (ROS) scavenger activity, which assisted its anti-inflammatory activity. From the bioassay-coupled chromatographic profile, chlorogenic acids were found to dominate the anti-inflammatory effects of LJEE. Moreover, LJ water extract (LJWE) demonstrated an interrupting effect on the severe acute respiratory syndrome coronavirus-2 spike protein (SARS-CoV-2-Spike)/angiotensin-converting enzyme 2 (ACE2) binding. In conclusion, the obtained results not only supported the traditional use of LJ for heat-clearance, but also suggested its potential application in daily health care during the COVID-19 pandemic.

Mass spectrometry of short peptides reveals common features of metazoan peptidergic neurons.

The evolutionary origins of neurons remain unknown. Although recent genome data of extant early-branching animals have shown that neural genes existed in the common ancestor of animals, the physiological and genetic properties of neurons in the early evolutionary phase are still unclear. Here, we performed a mass spectrometry-based comprehensive survey of short peptides from early-branching lineages Cnidaria, Porifera and Ctenophora. We identified a number of mature ctenophore neuropeptides that are expressed in neurons associated with sensory, muscular and digestive systems. The ctenophore peptides are stored in vesicles in cell bodies and neurites, suggesting volume transmission similar to that of cnidarian and bilaterian peptidergic systems. A comparison of genetic characteristics revealed that the peptide-expressing cells of Cnidaria and Ctenophora express the vast majority of genes that have pivotal roles in maturation, secretion and degradation of neuropeptides in Bilateria. Functional analysis of neuropeptides and prediction of receptors with machine learning demonstrated peptide regulation of a wide range of target effector cells, including cells of muscular systems. The striking parallels between the peptidergic neuronal properties of Cnidaria and Bilateria and those of Ctenophora, the most basal neuron-bearing animals, suggest a common evolutionary origin of metazoan peptidergic nervous systems.

Death anxiety as mediator of relationship between renunciation of desire and mental health as predicted by Nonself Theory.

In the present paper, we report two studies examining the relationships among renunciation of desires, death anxiety, and mental health. In the first study, we constructed the Desire Questionnaire (DQ), which measures success in renouncing certain desire. The DQ has satisfactory psychometric properties. In the second study, 501 adults from a Chinese society ranging in age from 17 to 84 years (M = 35.58, SD = 14.76) completed the DQ, the Death Anxiety Scale (DAS), and the Chinese Health Questionnaire (CHQ), which measures mental health and the presence of psychiatric symptoms. As predicted, DQ had significant negative correlations with both DAS (p < 0.05) and CHQ (p < 0.01). DAS had a significant positive correlation with CHQ (p < 0.01). In the linear mediation model, DAS was found to partially mediate the relationship between DQ and CHQ (ß = - 0.18, p < 0.001). These results suggest that the negative effect of poor control of desires on mental health can be partially accounted for by death anxiety. These findings imply that training in eliminating desires can be a successful strategy to improve mental health. These results also support the Nonself Theory as a theory of death anxiety and show its relevance to the relationship between nonself and mental health.

Enlarged cavum septi pellucidi Z-scores in fetuses with trisomy 18.

OBJECTIVE: We aim to establish a formula calculating the fetal cavum septi pellucidi (CSP) width Z-scores and compare CSP width between the normal fetus and 18-trisomy fetus. METHODS: In this retrospective study, 608 normal fetuses and 71 fetuses with the 18-trisomy syndrome were included. Z-scores were calculated after the acquisition of CSP images. Normal CSP width Z-scores formulae were constructed based on gestational age (GA) by performing a standard regression analysis followed by weighted regression of absolute residual values. Subsequently, the Mann-Whitney U test was used to compare the CSP width Z-scores between normal and 18-trisomy groups. RESULTS: Formulae calculating CSP width Z-scores were constructed. Normal fetal CSP width was significantly correlated with GA (R2 = 0.50, p < .01). In 18-trisomy group, 69% (34/49) fetuses displayed enlarged fetal CSP width and CSP width Z-scores (p < .01). CONCLUSIONS: The CSP width Z-scores formulae established in the current study can provide a quantitative basis for the prenatal diagnosis of 18-trisomy syndrome. Enlarged CSP width Z-score may serve as a novel prenatal diagnostic marker for the 18-trisomy syndrome.

Ultrasound in the prediction of birthweight discordance in dichorionic twins.

INTRODUCTION: Large birthweight discrepancy has been identified as a risk factor for perinatal morbidity and mortality in twin pregnancies. However, it remains unclear whether such discordance can be predicted by various biological indices with specific cut-off values, and how these depend on the gestational age. We aimed to determine the most effective way to predict large birthweight discordance at various gestational ages. MATERIAL AND METHODS: A retrospective cohort study of dichorionic twins, live-born between 2008 and 2018, was conducted. Discordances in biparietal diameter, head circumference, humerus and femur length, abdominal circumference, and estimated fetal weight were calculated-([larger twin - smaller twin] / larger twin) × 100%-and compared between those with and without a large birthweight discordance (≥20%). Receiver operating characteristic curves were constructed to analyze the predictive characteristics of each parameter. RESULTS: Of 598 dichorionic twin pregnancies included, 83 (13.9%) had a birthweight discordance ≥20%. Group differences in biparietal diameter and head circumference discordance were the earliest to emerge (before 20 weeks of gestation), but became insignificant after 36 weeks, followed by humerus and femur length, estimated fetal weight discordance (after 20 weeks), and abdominal circumference discordance (after 28 weeks). The best predictors (with cut-off values) were discordance in biparietal diameter ≥7.8% at <20 weeks, head circumference ≥4.5% at 20-23+6  weeks, humerus length ≥4.5% at 24-27+6  weeks, and estimated fetal weight discordance (≥11.6% at 28-31+6  weeks, ≥10.5% at 32-35+6  weeks, and ≥15.0% ≥36 weeks), with sensitivity and specificity of 52%-77% and 69%-82%, respectively. CONCLUSIONS: Different predictors and cut-off values may be useful for predicting large inter-twin birthweight discordance in dichorionic twins at different gestational ages. It is more accurate to use biparietal diameter and head circumference discordance in the early second trimester, humerus length discordance in the late second trimester, and estimated fetal weight discordance in the third trimester.

Automatic Measurements of Fetal Lateral Ventricles in 2D Ultrasound Images Using Deep Learning.

Measurement of the width of fetal lateral ventricles (LVs) in prenatal ultrasound (US) images is essential for antenatal neuronographic assessment. However, the manual measurement of LV width is highly subjective and relies on the clinical experience of scanners. To deal with this challenge, we propose a computer-aided detection framework for automatic measurement of fetal LVs in two-dimensional US images. First, we train a deep convolutional network on 2,400 images of LVs to perform pixel-wise segmentation. Then, the number of pixels per centimeter (PPC), a vital parameter for quantifying the caliper in US images, is obtained via morphological operations guided by prior knowledge. The estimated PPC, upon conversion to a physical length, is used to determine the diameter of the LV by employing the minimum enclosing rectangle method. Extensive experiments on a self-collected dataset demonstrate that the proposed method achieves superior performance over manual measurement, with a mean absolute measurement error of 1.8 mm. The proposed method is fully automatic and is shown to be capable of reducing measurement bias caused by improper US scanning.

Evaluation of the clinical diagnostic value of traditional inflammatory markers and novel biomarkers in intracellular bacterial bloodstream infections.

OBJECTIVES: The clinical symptoms of the patients with intracellular bacterial bloodstream infections (Intra-bac BSIs) are atypical, and no early and accurate diagnostic biomarkers exist, which can easily lead to misdiagnosis, inappropriate and delayed treatment. Therefore, it is imperative to find novel biomarkers to help clinical diagnosis of Intra-bac BSIs. The present study was initiated to evaluate the diagnostic values of traditional inflammatory biomarkers (PCT, WBC and NEU% in identifying the patients with Intra-bac BSIs, and to further explore into the possibility of using suPAR and sCD14-ST as novel biomarkers for Intra-bac BSIs. METHODS: A multi-center retrospective study was conducted in three teaching hospitals in Chongqing. A total of 146 cases with BSIs, including 73 cases with Intra-bac BSIs and 73 cases with extracellular bacterial BSIs (Extra-bac BSIs) were enrolled in the retrospective study. We then prospectively enrolled 34 patients with Intra-bac BSIs, 34 patients with Extra-bac BSIs, 34 patients with viral infection and with normal medical examination results as a control group for further detection of sCD14-ST and suPAR by ELISA. RESULTS: PCT levels, WBC counts and NEU% in patients with Intra-bac BSIs were not increased or minimally increased, they were significantly lower than that with Extra-bac BSIs (P < 0.05), especially those with the Brucella bacterial BSIs, demonstrated a respective negative rate of 84% and 92% for PCT and WBC counts. In the prospective study, the levels of suPAR and sCD14-ST in both the Intra-bac BSIs and the Extra-bac BSIs groups were significantly higher than those in the viral infection group and normal control group (P < 0.05). The areas under the curve (AUC) of Intra-bac BSIs were 0.830 for suPAR, and 0.855 for sCD14-ST. The sensitivity, specificity, Youden's index for suPAR and sCD14-ST were respectively 76.5%, 88.2%, 0.647 and 94.1%, 64.7%, 0.588. CONCLUSIONS: Our multi-center study demonstrated that while the traditional inflammatory markers such as PCT, WBC counts, NEU% could not be served as promising diagnostic markers for Intra-bac BSIs; CRP can help guide the diagnosis of Intra-bac BSIs; Both suPAR and sCD14-ST could be considered as novel diagnostic biomarkers for Intra-bac BSIs as they showed good diagnostic accuracies in Intra-bac BSIs, especially suPAR.

Prediction of cesarean hysterectomy in placenta previa complicated with prior cesarean: a retrospective study.

BACKGROUND: The prevalence of both placenta previa and cesarean are on the rise. Multiple adverse outcomes are critically increased when placenta previa is subsequent to prior cesarean. The purpose of the present study is to develop a pre-surgical method for predicting adverse outcomes in pregnancy complicated with both placenta previa and prior cesarean. METHODS: Clinical data was obtained from the medical history system at the First Affiliated Hospital of Sun Yat-sen University from February 2003 to December 2016. All cases with a final diagnosis of "placenta previa/low lying placenta (ICD:O44.001-105)" and "scarred uterus complicated with pregnancy (ICD: O34.200-202)" were collected and reviewed. Hysterectomy was taken as the primary outcome; and blood loss was taken as the secondary outcome. RESULTS: Of 219 pregnant women in the final analysis, 25 received a hysterectomy following delivery, and 48 had blood loss exceeding 1000 ml. Pre-surgical risk factors for hysterectomy are ultrasonic signs of vascular lacunae, central placenta previa, and loss of normal hypoechoic retroplacental zone. A pre-surgical predictive equation referred to as "Hysterectomy Index in Placenta Previa with Prior cesarean (HIPs)" was generated and each risk factor was weighted to create an 8-point scale. This index yielded an area under the curve of 0.972 for the prediction of hysterectomy. CONCLUSIONS: Application of the HIPs score may provide an effective pre-surgical prediction of cesarean hysterectomy in pregnant women complicated with both placenta previa and prior cesarean.

What can be inferred if the fetal increased nuchal translucency thickness changes?

Objectives: To study the perinatal outcomes in the women who's the different changes of an increased fetal nuchal translucency thickness.Methods: Since 2013-2016, the pregnant women whose initial measurement of fetal nuchal translucency (NT) ≥ 3.5 mm would be invited to scan the NT again after a week. Between the two measurements over 1 mm, defined as "change". According to different results between two measurements, they were divided into three groups: unchanged group, thinned group and thicken group. To follow-up and compare the perinatal outcomes among the three groups.Results: One hundred seventy-five cases met our criteria and were retrieved in the study. There are 90 cases of the unchanged group, 60 cases of the thinned group and 25 cases of thicken group. Among three groups, the chromosomal abnormalities rate is 11.11, 21.67, and 60.0% respectively, the structure abnormalities rate is 10.0, 8.51, and 20.0%, the normal delivery rate is 76.67, 70.0, and 28.0%. There all have the significantly differences in statistics except the structure abnormalities rate.Conclusion: The chromosomal abnormalities rate and adverse perinatal outcome rate were worse if NT continues to thicken. However, the perinatal outcome of the NT thinned group is no better than the NT unchanged case.

Prenatal diagnosis of chromosomal aberrations in fetuses with conotruncal heart defects by genome-wide high-resolution SNP array.

Objectives: To explore chromosomal variations, including copy number variations (CNVs), in fetuses with conotruncal heart defect (CTD).Methods: During a 5-year period, a total of 129 fetuses with ascertained CTDs were investigated for chromosomal abnormalities using quantitative fluorescence PCR (QF-PCR) and chromosomal microarray analysis (CMA). Fetuses were divided into two subgroups: benign group (with normal QF-PCR results and benign CNVs) and nonbenign group [with aneuploidies, nonbenign CNVs [pathogenic CNVs and CNVs of unknown significance (VOUS)]. Data on fetal structural malformations, chromosomal variations, and pregnancy outcomes were collected and compared.Results: Of the 129 cases, 17 were found to have common aneuploidies. In the remaining 112 cases with normal a QF-PCR result, pathogenic CNVs, CNVs of VOUS, and benign CNVs were identified in 5.3, 5.3, and 4.5%, respectively. Compared with benign group, fetuses in nonbenign group had a significantly higher rate of neurologic defects (13.8 versus 3.0%, p < .05), overall extracardiac anomalies (86.2 versus 45.0%, p < .05), and perinatal death (57.1 versus 18.4%, p < .05), whereas, no significant difference in that of associated cardiovascular anomalies was noted (48.2 versus 46.0%, p = .29). Among the extracardiac anomalies, thymus abnormalities were strongly associated with nonbenign CNVs (33.3 versus 1% of fetuses in benign group, p < .05).Conclusions: Pathogenic CNVs, in addition to chromosomal aneuploidies, contributed to the pathogenesis of CTD. The presence of associated extracardiac anomalies including thymus abnormalities correlated with a higher probability of nonbenign chromosomal variations, which was associated with an unfavorable outcome.

Evaluation of Cervical Elastography for Prediction of Spontaneous Preterm Birth in Low-Risk Women: A Prospective Study.

OBJECTIVES: The aim of this study was to determine whether cervical elastographic parameters in addition to cervical length (CL) during the 3 trimesters of pregnancy would be predictive of spontaneous preterm birth (sPTB) among low-risk women. METHODS: This work was a prospective nested case-control study evaluating cervical elastographic parameters and CL in low-risk women during the 3 trimesters of pregnancy. A binary logistic regression analysis was used to calculate significant covariates for prediction of sPTB. The area under the curve of the prediction model was calculated by using a receiver operating characteristic curve. RESULTS: There were 286 women (26 cases and 260 controls) included in the analysis. The parameters of cervical elasticity became softened and heterogeneous during the 3 trimesters of pregnancy in both women with and without sPTB. The differences in the mean strain value at the internal os of the cervix (IOS), ratio (strain ratio of the internal os to the external os) during the second trimester and the IOS during the third trimester between the groups had statistical significance (P < .01; P = .01; P < .01, respectively). The CL had no association with sPTB during the 3 trimesters. The IOS during the second trimester was a better predictor of sPTB, with an area under the curve of 0.730, and sensitivity was 72.73%. CONCLUSIONS: We observed multiple elastographic parameters and demonstrated the physiologic changes in the cervix during the 3 trimesters of pregnancy. Furthermore, we found that the IOS during the second trimester can be helpful in predicting sPTB. However, the CL had no association with sPTB during the 3 trimesters of pregnancy.

Quantitative elastography of cervical stiffness during the three trimesters of pregnancy with a semiautomatic measurement program: A longitudinal prospective pilot study.

AIM: To assess the reproducibility of a semiautomatic quantification tool for cervical stiffness and evaluate the normal changes in cervical elasticity during the three trimesters of pregnancy. METHODS: This longitudinal prospective pilot study evaluated cervical elasticity during the three trimesters of pregnancy (11-14, 20-24 and 28-32 weeks) in women with singleton pregnancies. Women with a history of conization, cerclage, cervical Naboth cysts (diameter > 10 mm), cervical tumors, or uterine malformation were excluded. A semiautomatic tool was used to evaluate the stiffness of the whole cervix and the internal and external cervical os with multiple quantitative elasticity parameters and the cervical length (CL) on the sagittal view via transvaginal elastography. Intraclass correlation coefficients (ICC) and Bland-Altman analysis were used to assess intra- and interobserver variability. E-Cervix parameters during the three trimesters were compared using the Friedman test. RESULTS: In total, 217 women with 651 strain examinations during the three trimesters were included. The intra- and interobserver ICC for the E-Cervix parameters ranged from 0.947 to 0.991 and 0.855 to 0.989, respectively. There were significant differences in all parameters among the three trimesters. Cervical elasticity showed significant softening and became heterogeneous during the three trimesters. The median CL was significantly shorter in the first trimester than in the second and third trimesters (P = 0.004, P < 0.001). CONCLUSION: E-Cervix provides a graphical tool for operators to easily define regions of interest and obtain multiple repeatable measures of elasticity. The normal references for E-Cervix parameters during the three trimesters reflect the physiological cervical changes during pregnancy.

Quantitative cervical elastography: a new approach of cervical insufficiency prediction.

OBJECTIVES: To establish methodological criteria for the clinical application of E-cervix technology in non-pregnant women, evaluate cervical differences between non-pregnant CI patients and normal women, and explore the predictive value of E-cervix for CI in non-pregnant women. METHODS: In all, 46 non-pregnant women with CI and 46 non-pregnant women with full-term pregnancy experience were included. Elastic parameters (HR, IOS, EOS, IOS/EOS, CL) of the cervix were measured by transvaginal examination with a mid-sagittal section as the ROI, followed by examination of the whole cervix. The pressure of the probe on the cervix was divided into three levels. The elastic data of three consecutive images were separately obtained by two doctors for three pressure levels. Image stability and the effects of pressure were evaluated and the repeatability of the measurements was tested. In the case and control groups, cervical elasticity images were selected by standardized operation methods. Differences in the parameters between the two groups were determined and the diagnostic efficiency of each parameter was analyzed. RESULTS: The HR, IOS, and EOS showed significant differences when measured on different sequential images obtained by continuous mapping (p < 0.05). The elastic parameters obtained from the first and last two images were significantly different (p < 0.05) and there were no significant differences between the elastic parameters obtained from the last two images (p > 0.05). The HR, IOS, EOS, and IOS/EOS showed significant differences among the pressure levels (p < 0.05), while the IOS showed a significant difference only between grades 0 and 2 (p < 0.05). E-cervix showed good repeatability within and among operators. The elastic parameters obtained by E-cervix in the CI group and control group were significantly different. ROC curve analysis showed that the HR was the most sensitive index for diagnosing CI. CONCLUSION: In E-cervix data acquisition, the first image should be excluded and the probe should not put pressure on the cervix. E-cervix has good retest and inter-observer reliability. Compared with normal women, CI patients showed a relatively softer and shorter cervix. E-cervix can be used as an important diagnostic tool for assessing cervical strain.