Identification of a novel monocyte/macrophage-related gene signature for predicting survival and immune response in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous hematological tumor with poor immunotherapy effect. This study was to develop a monocyte/macrophage-related prognostic risk score (MMrisk) and identify new therapeutic biomarkers for AML. We utilized differentially expressed genes (DEGs) in combination with single-cell RNA sequencing to identify monocyte/macrophage-related genes (MMGs). Eight genes were selected for the construction of a MMrisk model using univariate Cox regression analysis and LASSO regression analysis. We then validated the MMrisk on two GEO datasets. Lastly, we investigated the immunologic characteristics and advantages of immunotherapy and potential targeted drugs for MMrisk groups. Our study identified that the MMrisk is composed of eight MMGs, including HOPX, CSTB, MAP3K1, LGALS1, CFD, MXD1, CASP1 and BCL2A1. The low MMrisk group survived longer than high MMrisk group (P < 0.001). The high MMrisk group was positively correlated with B cells, plasma cells, CD4 memory cells, Mast cells, CAFs, monocytes, M2 macrophages, Endothelial, tumor mutation, and most immune checkpoints (PD1, Tim-3, CTLA4, LAG3). Furthermore, drug sensitivity analysis showed that AZD.2281, Axitinib, AUY922, ABT.888, and ATRA were effective in high-risk MM patients. Our research shows that MMrisk is a potential biomarker which is helpful to identify the molecular characteristics of AML immunology.

Fabrication of cinnamon essential oil nanoemulsions with high antibacterial activities via microfluidization.

The high volatility and hydrophobicity of cinnamon essential oils (CiEO) limited their practical application. To enhance their stability and antibacterial activity, nanoemulsions encapsulating CiEO were prepared using hydroxypropyl-ß-cyclodextrin/lauroyl arginate (HPCD/LAE) inclusion complexes through high-pressure microfluidization (HPM). Effects of HPM parameters on the stability and antibacterial properties of nanoemulsion were investigated. Results revealed that increased processing pressure and cycle numbers were associated with reduced droplet size and greater homogeneity in CiEO distribution. Storage and thermal stability were optimized at 100 MPa and seven cycles. Moreover, the nanoemulsions showed strong synergistic antibacterial against E. coli (19.79 mm) and S. aureus (23.61 mm) compared with LAE (11.52 mm and 12.82 mm, respectively) and CiEO alone (13.26 mm and 17.68 mm, respectively). This study provided new information for constructing CiEO nanoemulsion, which is suitable for use in the food industry.

Effects of dietary fiber on maternal health in pregnant women with metabolic syndrome risk: a randomized controlled trial.

Metabolic Syndrome (MetS) during pregnancy can lead to complications such as gestational diabetes mellitus (GDM) and hypertensive disorders. In this study, we sought to examine the influence of dietary fiber, from both food sources and soluble fiber supplementation, on the metabolic health and overall pregnancy outcomes of women at high risk of MetS. We conducted a randomized controlled trial involving 376 women between 11 and 13 weeks of gestation. To evaluate dietary fiber intake, we performed an exhaustive dietary component analysis using a food frequency questionnaire. Additionally, the participants in the intervention group received daily soluble fiber supplements until delivery. All participants underwent nutritional consultations and metabolic health assessments at three distinct stages of pregnancy (GW 11-13, GW 24-26, and GW 32-34). Our findings revealed a significant correlation between insufficient dietary fiber intake and an increased risk of GDM, even after adjusting for variables such as maternal age and pre-pregnancy BMI. We also noted that a high total dietary fiber intake was associated with reduced changes in triglyceride levels. In addition, the intervention group showed lower need for constipation medication, and soluble fiber supplementation may offer potential benefits for GDM patients. Importantly, our study verified the safety of long-term soluble fiber supplementation during pregnancy. Our results underscore the importance of adequate fiber intake, particularly from dietary sources, for the metabolic health of pregnant women. Moreover, our findings suggest that early fiber supplementation may benefit pregnant women experiencing constipation or those diagnosed with GDM.

Exploring the relationship between starch structure and physicochemical properties: The impact of extrusion on highland barley flour.

Highland barley (HB) is an intriguing plateau cereal crop with high nutrition and health benefits. However, abundant dietary fiber and deficient gluten pose challenges to the processing and taste of whole HB products. Extrusion technology has been proved to be effective in overcoming these hurdles, but the association between the structure and physicochemical properties during extrusion remains inadequately unexplored. Therefore, this study aims to comprehensively understand the impact of extrusion conditions on the physicochemical properties of HB flour (HBF) and the multi-scale structure of starch. Results indicated that the nutritional value of HBF were significantly increased (soluble dietary fiber and ß-glucan increased by 24.05%, 19.85% respectively) after extrusion. Typical underlying mechanisms based on starch structure were established. High temperature facilitated starch gelatinization, resulting in double helices unwinding, amylose leaching, and starch-lipid complexes forming. These alterations enhanced the water absorption capacity, cold thickening ability, and peak viscosity of HBF. More V-type complexes impeded amylose rearrangement, thus enhancing resistance to retrogradation and thermal stability. Extrusion at high temperature and moisture exhibited similarities to hydrothermal treatment, partly promoting amylose rearrangement and enhancing HBF peak viscosity. Conversely, under low temperature and high moisture, well-swelled starch granules were easily broken into shorter branch-chains by higher shear force, which enhanced the instant solubility and retrogradation resistance of HBF as well as reduced its pasting viscosity and the capacity to form gel networks. Importantly, starch degradation products during this condition were experimentally confirmed from various aspects. This study provided some reference for profiting from extrusion for further development of HB functional food and "clean label" food additives.

The prognostic role of 18F-FDG PET/CT-based response evaluation in children with stage 4 neuroblastoma.

OBJECTIVES: To evaluate the association between metabolic response on 18F-FDG PET/CT and long-term survival in children with neuroblastoma (NB). METHODS: A total of 39 consecutive children with newly diagnosed stage 4 NB undergoing both 18F-FDG PET/CT imaging at baseline and after chemotherapy were retrospectively analyzed. The associations between metabolic parameters, including SUVmax of the lesion with the most intense 18F-FDG uptake at baseline (SUVb), after chemotherapy (SUVe), and the percentage change between SUVb and SUVe, and long-term survival were evaluated. RESULTS: With a median follow-up of 56 months, 22 patients who had achieved complete resolution on PET (no residual 18F-FDG uptake higher than the surrounding backgrounds) after chemotherapy had superior 5-year overall survival (OS) (73.6% vs. 39.0%, p = 0.044). SUVb > 6.9 indicated significantly poorer 5-year event-free survival (EFS) (12.5% vs. 59.3%, p = 0.005), as did SUVe > 1.2 (18.8% vs. 41.7%, p = 0.041). Children with SUVe > 1.2 had shorter 5-year OS (33.9% vs. 75.0%, p = 0.018). Multivariate analysis identified SUVe > 1.2 as an independent predictor for both EFS [hazard ratio (HR), 3.479, 95% CI, 1.381-8.761, p = 0.008] and OS (HR, 6.948, 95% CI, 1.663-29.025, p = 0.008), while SUVb > 6.9 was a predictor for EFS (HR, 2.889, 95% CI, 1.064-7.842, p = 0.037). Among 11 children with both SUVb > 6.9 and SUVe > 1.2, all experienced disease progression or relapse within 2 years since diagnosis. CONCLUSION: 18F-FDG PET/CT could be of useful to evaluate treatment response in children with stage 4 NB. CLINICAL RELEVANCE STATEMENT: 18F-FDG PET/CT after chemotherapy exhibits prognostic significance in neuroblastoma and holds potential as an alternative imaging modality for response evaluation, especially in cases with metaiodobenzylguanidine-nonavid or persistent avid disease. KEY POINTS: The prognostic value of chemotherapy response on 18F-FDG PET/CT in advanced neuroblastoma is unknown. Higher 18F-FDG uptake after chemotherapy was associated with worse long-term event-free survival and overall survival. 18F-FDG PET/CT after chemotherapy holds prognostic significance in children with stage 4 neuroblastoma.

Insight into the structural characteristics of self-assembled liposome with epigallocatechin gallate/alcohol dehydrogenase.

In this study, the encapsulation and structural characteristics of the self-assembled liposome formed by epigallocatechin gallate (EGCG) and alcohol dehydrogenase (ADH) were studied. According to the results, EGCG significantly increased the catalytic activity of ADH with a 33.33 % activation rate and the liposomes were able to entrap EGCG-ADH with an effectiveness of 88.94 %. The self-assembled monolayers had nanometer-sized particles, and the excellent self-assembled system was demonstrated by the low PDI value and high surface absolute potential. The scanning electron microscope showed that the self-assembled liposome was honeycomb, groove-shaped, and rough. The spectroscopic results showed that EGCG-ADH complex was formed through hydrogen bond, which changed the secondary structure of the liposome, and verified EGCG-ADH liposome system was successfully prepared. In vitro digestion experiments showed that the gastrointestinal tolerance and antioxidant activity of EGCG-ADH liposomes were significantly higher than those of free EGCG-ADH.

Identification of shared gene signatures and biological mechanisms between preeclampsia and polycystic ovary syndrome.

Preeclampsia (PE) is one of the most common complications of pregnancy and polycystic ovary syndrome (PCOS) is a prevalent metabolic and endocrinopathy disorder in women of reproductive age. Identifying the shared genetic signatures and molecular mechanisms between PCOS and PE was the objective of this study. The intersections of WGCNA module genes, PPI module genes, and PPI hub genes revealed that 8 immunity-related genes might be shared causative genes of PE and PCOS. Further, qRT-PCR results showed that TSIX/miR-223-3p/DDX58 might play a crucial role in immune dysregulation in PE and PCOS and Spearman rank correlation analysis results illustrated the potential of DDX58 as a novel diagnostic and therapeutic target for PE and PCOS. Our study demonstrated a common disease pathway model TSIX/miR-223-3p/DDX58, illustrating that immune dysregulation may be a possible mechanism of PE and PCOS, and revealed that DDX58 might be a novel predictive target for PE and PCOS.

[Effects of Continuous Annual Crop Rotation and Fallow on Soil Aggregate Stability and Organic Carbon].

In order to explore the effects of continuous annual crop rotation and fallow on aggregate stability and organic carbon content in red soil, the red soil in sloping farmland was taken as the research object, and the water-stable aggregates and organic carbon content were determined using the wet sieve method and potassium dichromate-concentrated sulfuric acid external heating method, respectively. The changes in soil aggregate stability and organic carbon content under the four treatments of maize-vetch-maize rotation (M-V-M), maize-pea-maize rotation (M-P-M), maize-fallow-maize (M-F-M), and annual fallow (F-F-F) from 2020 to 2022 and the relationships between them were analyzed. The results showed that in 2021 and 2022, the contents of > 2 mm aggregates treated with F-F-F, M-V-M, and M-P-M were significantly increased by 67.01%-100.92%, 29.71%-33.67%, and 29.68%-38.07%, respectively, compared with that treated with M-F-M. In 2021 and 2022, the stability parameters of F-F-F and M-V-M were significantly higher than those of M-F-M (P < 0.05). The content of > 2 mm aggregates, geometric mean diameter (GMD), and mean weight diameter (MWD) under the M-V-M treatment and R0.25 (> 0.25 mm aggregate contents), MWD and > 2 mm aggregate contents under the F-F-F treatment increased with the increase in fallow years, whereas the content of 1-2 mm and < 0.25 mm under the F-F-F treatment decreased with the increase in fallow years. Both green manure rotation and fallow treatment could increase the SOC content, and the SOC content of F-F-F and M-V-M treatment increased with the extension in age. Correlation analysis showed that SOC content was significantly positively correlated with R0.25 and GMD under all treatments. R0.25 and GMD under the F-F-F treatment and GMD and MWD under M-V-M were significantly positively correlated with SOC content. The results showed that continuous annual crop rotation and fallow was beneficial to improve the content of soil macro-aggregates, aggregate stability, and SOC content, which could provide theoretical basis for the implementation of reasonable continuous annual crop rotation and fallow patterns and soil erosion control in red soil areas of sloping farmland in southern China.

Discovery of HC-7366: An Orally Bioavailable and Efficacious GCN2 Kinase Activator.

A series of activators of GCN2 (general control nonderepressible 2) kinase have been developed, leading to HC-7366, which has entered the clinic as an antitumor therapy. Optimization resulted in improved permeability compared to that of the original indazole hinge binding scaffold, while maintaining potency at GCN2 and selectivity over PERK (protein kinase RNA-like endoplasmic reticulum kinase). The improved ADME properties of this series led to robust in vivo compound exposure in both rats and mice, allowing HC-7366 to be dosed in xenograft models, demonstrating that activation of the GCN2 pathway by this compound leads to tumor growth inhibition.

Probing Coordination Number of Single-Atom Catalysts by d-Band Center-Regulated Luminescence.

It is essential to probe the coordination number (CN) because it is a crucial factor to ensure the catalytic capability of single-atom catalysts (SACs). Currently, synchrotron X-ray absorption spectroscopy (XAS) is widely used to measure the CN. However, the scarcity of synchrotron X-ray source and complicated data analysis restrict its wide applications in determining the CN of SACs. In this contribution, we have developed a d-band center-regulated acetone cataluminescence (CTL) probe for a rapid screening of the CN of Pt-SACs. It is disclosed that the CN-triggered CTL is attributed to the fact that the increased CN could induce the downward shift of d-band center position, which assists the acetone adsorption and promotes the subsequent catalytic reaction. In addition, the universality of the proposed acetone-CTL probe is verified by determining the CN of Fe-SACs. This work has opened a new avenue for exploring an alternative to synchrotron XAS for the determination of CN of SACs and even conventional metal catalysts through d-band center-regulated CTL.

18 F-FDG PET/CT in a Case of Clear Cell Sarcoma of the Kidney.

ABSTRACT: 18 F-FDG PET/CT was performed in a 1-year-old girl who had a heterogeneous mass in the right abdominal cavity revealed by abdominal ultrasound. A heterogeneous mass with internal necrosis, cystic changes, and hemorrhage in the right kidney, accompanied by a slight increase of FDG uptake, was observed in FDG PET/CT. Malignant renal tumor was considered, and Wilms tumor was preferentially suspected. However, the mass was demonstrated as clear cell sarcoma of the kidney by histopathological examination.

Association of maternal serum uric acid levels with LBW/SGA: a large retrospective cohort study.

BACKGROUND: Elevated maternal serum uric acid (UA) levels were associated with adverse perinatal outcomes. This study aimed to examine the association between UA and the risk of low birth weight (LBW) / small for gestational age (SGA). METHODS: A cohort study of women delivered in Shanghai maternity hospital was included between 2017 and 2021. Electronic medical records were utilized to extract information and antenatal care records. The cut-off value of UA was 360 µmol/L. The outcome was LBW/SGA, with LBW defined as birth weight below 2500 g and SGA indicating birth weight below the 10th percentile of average weight for gestational age. The assessment of SGA was based on the Chinese standard curve for birth weight at various gestational ages. Univariate, multivariate logistic regression models, restricted cubic spline were used in this study, with adjustments made for confounding factors. RESULTS: Sixty-nine thousand six hundred seventy-four live births and singleton pregnancies were included. The ratio of LBW/SGA was 3.3%/9%. Maternal UA levels were significantly negatively correlated with birth weight. High UA levels were associated with high risk of LBW/SGA, especially in third trimester. In BMI < 25 group, the risk of LBW increased to 2.35-fold (95%CI, 1.66-3.31) in hyperuricemic group (UA > 360 µmol/L). The SGA risk was 1.66-fold (95%CI, 1.37-2.00). Gestational hypertension (GH) with hyperuricemica increased the risk of LBW (aOR = 4.00, 95%CI, 2.01-7.93) and SGA (aOR = 2.63, 95%CI, 1.83-3.78). Preeclampsia (PE) with hyperuricemia increased the risk of LBW (aOR = 1.38, 95%CI, 0.63-3.03) and SGA (aOR = 1.81, 95%CI, 1.18-2.78). In delivery gestational week (DGW) ≥ 37 group, if UA > 360 µmol/L, the incidence of LBW increased to 2.46-fold (95%CI, 1.62, 3.73) and the incidence of SGA increased to 1.52-fold (95%CI, 1.24, 1.87). In DGW < 37 group, if UA > 360 µmol/L, the incidence of LBW increased to 2.70-fold (95%CI, 1.92, 3.80) and the incidence of SGA increased to 2.13-fold(95%CI, 1.50, 3.02). CONCLUSIONS: The study found an inverse correlation between UA levels and birth weight. High UA levels were associated with increased risk of LBW/SGA, particularly in third trimester. GH or PE complicated by hyperuricemia were found to have significantly higher risk of developing LBW/SGA. This relationship also existed in pregnant women with BMI < 25.

Deleting IP6K1 stabilizes neuronal sodium-potassium pumps and suppresses excitability.

Inositol pyrophosphates are key signaling molecules that regulate diverse neurobiological processes. We previously reported that the inositol pyrophosphate 5-InsP7, generated by inositol hexakisphosphate kinase 1 (IP6K1), governs the degradation of Na+/K+-ATPase (NKA) via an autoinhibitory domain of PI3K p85α. NKA is required for maintaining electrochemical gradients for proper neuronal firing. Here we characterized the electrophysiology of IP6K1 knockout (KO) neurons to further expand upon the functions of IP6K1-regulated control of NKA stability. We found that IP6K1 KO neurons have a lower frequency of action potentials and a specific deepening of the afterhyperpolarization phase. Our results demonstrate that deleting IP6K1 suppresses neuronal excitability, which is consistent with hyperpolarization due to an enrichment of NKA. Given that impaired NKA function contributes to the pathophysiology of various neurological diseases, including hyperexcitability in epilepsy, our findings may have therapeutic implications.

Metformin ameliorates mitochondrial damage induced by C9orf72 poly(GR) via upregulating AKT phosphorylation.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative diseases with no effective cure. GGGGCC repeat expansion in C9orf72 is the most common genetic cause of both ALS and FTD. A key pathological feature of C9orf72 related ALS/FTD is the presence of abnormal dipeptide repeat proteins translated from GGGGCC repeat expansion, including poly Glycine-Arginine (GR). In this study, we observed that (GR)50 conferred significant mitochondria damage and cytotoxicity. Metformin, the most widely used clinical drug, successfully relieved (GR)50 induced mitochondrial damage and inhibited (GR)50 related cytotoxicity. Further research revealed metformin effectively restored mitochondrial function by upregulating AKT phosphorylation in (GR)50 expressed cells. Taken together, our results indicated restoring mitochondrial function with metformin may be a rational therapeutic strategy to reduce poly(GR) toxicity in C9orf72 ALS/FTD patients.

Insight into the binding characteristics of epigallocatechin-3-O-gallate and alcohol dehydrogenase: Based on the spectroscopic and molecular docking analysis.

Alcohol dehydrogenase (ADH) is one of the pivotal enzymes for alcohol metabolism, which plays an important role in many physiological processes. In this study, the activation effects of epigallocatechin-3-O-gallate (EGCG) on ADH and the characteristics of the interaction were investigated via biochemical method, spectroscopy methods, and molecular docking. The results demonstrated that EGCG significantly increased the catalytic activity of ADH with a 33.33% activation rate and that EGCG blending slightly altered the microenvironment surrounding ADH aromatic amino acids, with an increase in the quantity of ß-sheet and a decrease in the α-helix. Through the thermal stability analysis, it is further shown that the interaction of the two affects the intra-molecular hydrogen bond formation of the protein, and the conformation is partially extended. Besides, a total of 8 residues in ADH participated in the docking with EGCG, among which Asp-227, Lys-231, Glu-234, Gly-365 and Glu-366 participated in the formation of hydrogen bonds. At the same time, EGCG and amino group of Lys-231 form a noncovalent bond through cation-π interaction. In particular, hydrogen bonding was beneficial to keep the stability of EGCG-ADH, which was the primary driver of ADH activity activation. The results supply a new way for EGCG to activate ADH and a theoretical basis for the development of anti-alcoholism products.

Functions, Mechanisms, and therapeutic applications of the inositol pyrophosphates 5PP-InsP5 and InsP8 in mammalian cells.

Water-soluble myo-inositol phosphates have long been characterized as second messengers. The signaling properties of these compounds are determined by the number and arrangement of phosphate groups on the myo-inositol backbone. Recently, higher inositol phosphates with pyrophosphate groups were recognized as signaling molecules. 5-Diphosphoinositol 1,2,3,4,6-pentakisphosphate (5PP-InsP5) is the most abundant isoform, constituting more than 90% of intracellular inositol pyrophosphates. 5PP-InsP5 can be further phosphorylated to 1,5-bisdiphosphoinositol 2,3,4,6-tetrakisphosphate (InsP8). These two molecules, 5PP-InsP5 and InsP8, are present in various subcellular compartments, where they participate in regulating diverse cellular processes such as cell death, energy homeostasis, and cytoskeletal dynamics. The synthesis and metabolism of inositol pyrophosphates are subjected to tight regulation, allowing for their highly specific functions. Blocking the 5PP-InsP5/InsP8 signaling pathway by inhibiting the biosynthesis of 5PP-InsP5 demonstrates therapeutic benefits in preclinical studies, and thus holds promise as a therapeutic approach for certain diseases treatment, such as metabolic disorders.

Outcome of monochorionic diamniotic twin pregnancy with selective intrauterine growth restriction, a single center study in China.

INTRODUCTION: This retrospective study aimed to evaluate clinical outcomes of monochorionic diamniotic (MCDA) twins with selective intrauterine growth restriction (sIUGR). MATERIALS AND METHODS: MCDA twins, either sIUGR and non-sIUGR, underwent expectant management from 2016 to 2019 in our hospital were included. sIUGR fetuses were classified into three types according to umbilical artery Doppler assessment. Non-sIUGR were considered as the control group. Outcomes were pregnancy outcomes and maternal complications. RESULTS: Forty-three sIUGR (type I: 23; type II: 14, and type III: 6) and 282 non-sIUGR fetuses were included. The sIUGR group had a significantly earlier birth, lower birth weight of the twins, larger inter-twin weight difference, lower Apgar score of the twins, and higher intrauterine fetal death (IUFD) than the non-sIUGR group (all p < 0.001). The same trend was found in the sIUGR type II group compared to type I and III groups. A significantly lower gestational diabetes rate (p = 0.01) and placenta weight (p < 0.001), and higher proportions of abnormal placental umbilical cord insertion (p < 0.001), and ultrasound Doppler monitoring indicators (p = 0.006) were found in the sIUGR group than the non-sIUGR group. CONCLUSIONS: The MCDA twins with sIUGR showed poorer outcomes than the non-sIUGR group. Doppler interrogation was a useful clinical marker for fetal outcome.

Gestational weight gain of multiparas and risk of primary preeclampsia: a retrospective cohort study in Shanghai.

BACKGROUND: In all studies conducted so far, there was no report about the correlation between excessive gestational weight gain (GWG) and the risk of preeclampsia (PE) in multiparas, especially considering that multiparity is a protective factor for both excessive GWG and PE. Thus, the aim of this retrospective cohort study was to determine whether GWG of multiparas is associated with the increased risk of PE. METHODS: This was a study with 15,541 multiparous women who delivered in a maternity hospital in Shanghai from 2017 to 2021, stratified by early-pregnancy body mass index (BMI) category. Early-pregnancy body weight, height, week-specific and total gestational weight gain as well as records of antenatal care were extracted using electronic medical records, and antenatal weight gain measurements were standardized into gestational age-specific z scores. RESULTS: Among these 15,541 multiparous women, 534 (3.44%) developed preeclampsia. The odds of preeclampsia increased by 26% with every 1 z score increase in pregnancy weight gain among normal weight women and by 41% among overweight or obese women. For normal weight women, pregnant women with preeclampsia gained more weight than pregnant women without preeclampsia beginning at 25 weeks of gestation, while accelerated weight gain was more obvious in overweight or obese women after 25 weeks of gestation. CONCLUSIONS: In conclusion, excessive GWG in normal weight and overweight or obese multiparas was strongly associated with the increased risk of preeclampsia. In parallel, the appropriate management and control of weight gain, especially in the second and third trimesters, may lower the risk of developing preeclampsia.

Clinical Outcome of Monochorionic Diamniotic Twins with Intrauterine Growth Restriction.

OBJECTIVE: This study investigated the clinical outcome of monochorionic diamniotic (MCDA) twins with selective intrauterine growth restriction (sIUGR). STUDY DESIGN: International Peace Maternal and Child Health Hospital of Shanghai ultrasound database was investigated to identify all MCDA delivered from January 2013 to December 2017. After identifying 43 pairs of MCDA twins with sIUGR and 282 pairs of normal MCDA twins, we compared clinical outcomes between the two groups. RESULTS: Compared with normal twins, sIUGR fetuses had significantly shorter gestational age at delivery, smaller average birth weight of both twins, more significant intertwin difference in birth weight, lower Apgar scores, and higher intrauterine fetal demise (IUFD) rate, and smaller placental weight. The rate of abnormal umbilical cord insertions and abnormal blood flow in the ductus venosus (DV) and middle cerebral artery (MCA) is significantly higher in the sIUGR group. In addition, the subtype analysis of sIUGR groups indicated the poorest outcomes in type II with no significant difference between type I and III. CONCLUSION: MCDA twins with sIUGR generally exhibited limited clinical outcomes than normal MCDA twins. These limitations are mainly associated with abnormal umbilical cord insertions and blood flow in the DV and MCA. Clinical outcomes differed among the three types of sIUGR, with type II having the worst prognosis and the highest IUFD rate. KEY POINTS: · sIUGR generally exhibited limited clinical outcomes than normal MCDA twins.. · These limitations are mainly associated with blood flow of the DV and MCA.. · sIUGR with type II has the worst prognosis and the highest IUFD rate..

Analysis of genetic testing in fetuses with congenital heart disease of single atria and/or single ventricle in a Chinese prenatal cohort.

OBJECTIVE: This study aimed to investigate the genetic etiologies of fetuses with single atria and/or ventricle (SA or/and SV) using different genetic detection methods in a Chinese prenatal cohort. METHODS: In this retrospective study, the various genetic results of 44 fetuses with SA and/or SV were analyzed. All 44 cases were tested by chromosomal microarray analysis (CMA) and karyotyping simultaneously, and 8 underwent whole exome sequencing (WES). Data on the pregnancy outcomes and neonatal prognoses were collected from medical records and postnatal follow-up. RESULTS: The whole cohort of 44 fetuses included 14 SA cases (31.8%), 12 SV cases (27.3%), and 18 SA and SV cases (40.9%). A total of 9 pathogenic genetic results were detected by conventional karyotyping, CMA and trio-WES, indicating an overall detection rate of 20.5% (9/44). Six pathogenic chromosomal abnormalities were identified by CMA among the 44 cases, showing a detection rate of 13.6% (6/44). Two microdeletions being missed by karyotyping were diagnosed by CMA, showing an additional diagnostic yield of 4.5% for CMA in present cohort(2/44). Three pathogenic variants in two fetuses were identified by WES, indicating an incremental diagnostic yield of 4.5%(2/44) for WES in fetuses with SA or/and SV. CONCLUSION: In this study, WES achieved an additional diagnostic yield of 4.5% in fetuses with SA or/and SV. WES is valuable for fetal prognosis assessment and could add diagnostic value for fetuses with SA and/or SV when CMA is negative. It would be a valuable technique for the identification of underlying pathogenic variants in prenatal cohorts.