Prenatal chromosomal microarray analysis and karyotyping in fetuses with isolated choroid plexus cyst: A retrospective case-control study.

OBJECTIVES: To evaluate the the diagnostic yield of chromosomal microarray analysis (CMA) in fetuses with isolated CPC (iCPC). METHODS: A total of 315 fetuses with iCPC (iCPC group) and 364 fetuses without abnormal ultrasound findings (control group) were recruited between July 2014 to March 2018. RESULTS: The overall diagnostic yield of chromosomal abnormalities by CMA and karyotyping in iCPC group was up to 4.1 %, higher than 1.4 % in the control group, p < 0.05. The detection rate of pathogenic or likely pathogenic copy number variants (CNVs) with clinical significance by CMA in iCPC group (1.3 %) was higher than in control group (0 %), p < 0.05. According to the type of chromosome abnormalities, the missed diagnosis rate of non-invasive prenatal testing (NIPT) was 1.6 % in our study. CONCLUSIONS: The presence of iCPC on ultrasound examination suggests a potential indication for genetic counseling. Karyotyping and chromosomal microarray analysis may be considered for fetuses with iCPC. It is important to be aware of the limitations of non-invasive prenatal testing, as there is a possibility of residual risk.

Malformations of cortical development: Fetal imaging and genetics.

BACKGROUND: Malformations of cortical development (MCD) are a group of congenital disorders characterized by structural abnormalities in the brain cortex. The clinical manifestations include refractory epilepsy, mental retardation, and cognitive impairment. Genetic factors play a key role in the etiology of MCD. Currently, there is no curative treatment for MCD. Phenotypes such as epilepsy and cerebral palsy cannot be observed in the fetus. Therefore, the diagnosis of MCD is typically based on fetal brain magnetic resonance imaging (MRI), ultrasound, or genetic testing. The recent advances in neuroimaging have enabled the in-utero diagnosis of MCD using fetal ultrasound or MRI. METHODS: The present study retrospectively reviewed 32 cases of fetal MCD diagnosed by ultrasound or MRI. Then, the chromosome karyotype analysis, single nucleotide polymorphism array or copy number variation sequencing, and whole-exome sequencing (WES) findings were presented. RESULTS: Pathogenic copy number variants (CNVs) or single-nucleotide variants (SNVs) were detected in 22 fetuses (three pathogenic CNVs [9.4%, 3/32] and 19 SNVs [59.4%, 19/32]), corresponding to a total detection rate of 68.8% (22/32). CONCLUSION: The results suggest that genetic testing, especially WES, should be performed for fetal MCD, in order to evaluate the outcomes and prognosis, and predict the risk of recurrence in future pregnancies.

Inverse association between maternal serum concentrations of trace elements and risk of spontaneous preterm birth: a nested case-control study in China.

Few studies have evaluated the joint effect of trace elements on spontaneous preterm birth (SPTB). This study aimed to examine the relationships between the individual or mixed maternal serum concentrations of Fe, Cu, Zn, Se, Sr and Mo during pregnancy, and risk of SPTB. Inductively coupled plasma MS was employed to determine maternal serum concentrations of the six trace elements in 192 cases with SPTB and 282 controls with full-term delivery. Multivariate logistic regression, weighted quantile sum regression (WQSR) and Bayesian kernel machine regression (BKMR) were used to evaluate the individual and joint effects of trace elements on SPTB. The median concentrations of Sr and Mo were significantly higher in controls than in SPTB group (P < 0·05). In multivariate logistic regression analysis, compared with the lowest quartile levels of individual trace elements, the third- and fourth-quartile Sr or Mo concentrations were significantly associated with reduced risk of SPTB with adjusted OR (aOR) of 0·432 (95 CI < 0·05). In multivariate logistic regression analysis, compared with the lowest quartile levels of individual trace elements, the third- and fourth-quartile Sr or Mo concentrations were significantly associated with reduced risk of SPTB with adjusted aOR of 0·432 (95 % CI 0·247, 0·756), 0·386 (95 % CI 0·213, 0·701), 0·512 (95 % CI 0·297, 0·883) and 0·559 (95 % CI 0·321, 0·972), respectively. WQSR revealed the inverse combined effect of the trace elements mixture on SPTB (aOR = 0·368, 95 % CI 0·228, 0·593). BKMR analysis confirmed the overall mixture of the trace elements was inversely associated with the risk of SPTB, and the independent effect of Sr and Mo was significant. Our findings suggest that the risk of SPTB decreased with concentrations of the six trace elements, with Sr and Mo being the major contributors.

Comprehensive application of multiple molecular diagnostic techniques in pre-implantation genetic testing for monogenic.

BACKGROUND: Pre-implantation genetic testing for monogenic disorders (PGT-M) is an effective approach to reducing the incidence of birth defects by preventing the transmission of inherited diseases to offspring. However, there are still controversies regarding the detection methods and transplantation of embryos. This paper aims to evaluate the effectiveness of different detection technologies applied to PGT-M through a retrospective analysis of clinical detection data. METHODS: The carrier status of pathogenic mutations and chromosomal copy number variants (CNVs) in 892 embryos was characterized using next-generation sequencing (NGS), single-nucleotide polymorphism (SNP) array, and PCR-based detection technologies. Clinical data from PGT-M cases were retrospectively analyzed to assess the effectiveness of these detection methods in identifying genetic abnormalities in embryos. RESULTS: A total of 829 embryos were analyzed, with 63 being unsuccessful. Our study revealed that the success rate of detecting deletional mutations using Gap-PCR 84.9%, which is lower than that of SNP array (98.7%) and NGS (92.5%). However, no significant difference was observed when detecting point mutations using any of the methods. These findings suggest that, when detecting deletional mutations, SNP array and NGS are more suitable choices compared to Gap-PCR. While SNP array may have a lower resolution and success rate (80.5%) in analyzing CNVs compared to NGS (95.5%), it may still be useful for revealing certain abnormal types. CONCLUSION: In conclusion, this study found that SNP analysis is advantageous for identifying polygenic and deletional mutations, whereas NGS is more cost-efficient for detecting common monogenic diseases. Additionally, SNP-based haplotyping and PCR-based direct detection of mutations can be used together to enhance the accuracy and success rates of PGT-M. Our findings offer valuable insights for PGT technicians in choosing suitable detection methods for patients.

A Semantic-Aware Attention and Visual Shielding Network for Cloth-Changing Person Re-Identification.

Cloth-changing person re-identification (ReID) is a newly emerging research topic that aims to retrieve pedestrians whose clothes are changed. Since the human appearance with different clothes exhibits large variations, it is very difficult for existing approaches to extract discriminative and robust feature representations. Current works mainly focus on body shape or contour sketches, but the human semantic information and the potential consistency of pedestrian features before and after changing clothes are not fully explored or are ignored. To solve these issues, in this work, a novel semantic-aware attention and visual shielding network for cloth-changing person ReID (abbreviated as SAVS) is proposed where the key idea is to shield clues related to the appearance of clothes and only focus on visual semantic information that is not sensitive to view/posture changes. Specifically, a visual semantic encoder is first employed to locate the human body and clothing regions based on human semantic segmentation information. Then, a human semantic attention (HSA) module is proposed to highlight the human semantic information and reweight the visual feature map. In addition, a visual clothes shielding (VCS) module is also designed to extract a more robust feature representation for the cloth-changing task by covering the clothing regions and focusing the model on the visual semantic information unrelated to the clothes. Most importantly, these two modules are jointly explored in an end-to-end unified framework. Extensive experiments demonstrate that the proposed method can significantly outperform state-of-the-art methods, and more robust features can be extracted for cloth-changing persons. Compared with multibiometric unified network (MBUNet) (published in TIP2023), this method can achieve improvements of 17.5% (30.9%) and 8.5% (10.4%) on the LTCC and Celeb-reID datasets in terms of mean average precision (mAP) (rank-1), respectively. When compared with the Swin Transformer (Swin-T), the improvements can reach 28.6% (17.3%), 22.5% (10.0%), 19.5% (10.2%), and 8.6% (10.1%) on the PRCC, LTCC, Celeb, and NKUP datasets in terms of rank-1 (mAP), respectively.

Epidemiology of birth defects based on a birth defects surveillance system in southwestern China and the associated risk factors.

Background: Birth defects (BDs) are associated with many potential risk factors, and its causes are complex. Objectives: This study aimed to explore the epidemiological characteristics of BDs in Guangxi of China and the associated risk factors of BDs. Methods: BDs data of perinatal infants (PIs) were obtained from the Guangxi birth defects monitoring network between 2016 and 2020. Univariate Poisson regression was used to calculate the prevalence-rate ratios (PRR) to explore the changing trends of BDs prevalence by year and the correlation between the regarding of characteristics of BDs (including infant gender, maternal age, and quarter) and BDs. Clinical characteristics of PIs with BDs and general characteristics of their mothers were documented, and Spearman correlation analysis was used to explore the potential associated risk factors of BDs. Results: Between 2016 and 2020, 44,146 PIs with BDs were monitored, with an overall BDs prevalence of 121.71 (95% CI: 120.58-122.84) per 10,000 PIs, showing a significant increase trend (PRR = 1.116, 95% CI: 1.108-1.123), especially the prevalence of congenital heart defects (CHDs) that most significantly increased (PRR = 1.300, 95% CI: 1.283-1.318). The 10 most common BDs were CHDs, polydactyly, congenital talipes equinovarus, other malformation of external ear, syndactyly, hypospadias, cleft lip with cleft palate, cleft lip, hemoglobin Bart's hydrops fetalis syndrome (BHFS), and congenital atresia of the rectum and anus. BDs were positively correlated with pregnant women's age (R = 0.732, P < 0.01) and education level (R = 0.586, P < 0.05) and having pre-gestational diabetes mellitus (PGDM)/gestational diabetes mellitus (GDM) (R = 0.711, P < 0.01), while when the pregnant women had a family history of a dead fetus (R = -0.536, P < 0.05) and a birth of a fetus with BDs (R = -0.528, P < 0.05) were negatively correlated with BDs. Conclusion: A significant increase in the prevalence of BDs was detected between 2016 and 2020 in Guangxi, especially the prevalence of CHDs that most significantly increased. Older maternal age, higher maternal education level, and having PGDM before pregnancy or GDM in early pregnancy were the risk factors for BDs.

Crosstalk between miR-144/451 and Nrf2 during Recovery from Acute Hemolytic Anemia.

miR-144/451 and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulate two antioxidative systems that have been identified to maintain redox homeostasis in erythroid cells by removing excess reactive oxygen species (ROS). Whether these two genes coordinate to affect ROS scavenging and the anemic phenotype, or which gene is more important for recovery from acute anemia, has not been explored. To address these questions, we crossed miR-144/451 knockout (KO) and Nrf2 KO mice and examined the phenotype change in the animals as well as the ROS levels in erythroid cells either at baseline or under stress condition. Several discoveries were made in this study. First, Nrf2/miR-144/451 double-KO mice unexpectedly exhibit similar anemic phenotypes as miR-144/451 single-KO mice during stable erythropoiesis, although compound mutations of miR-144/451 and Nrf2 lead to higher ROS levels in erythrocytes than single gene mutations. Second, Nrf2/miR-144/451 double-mutant mice exhibit more dramatic reticulocytosis than miR-144/451 or Nrf2 single-KO mice during days 3 to 7 after inducing acute hemolytic anemia using phenylhydrazine (PHZ), indicating a synergistic effect of miR-144/451 and Nrf2 on PHZ-induced stress erythropoiesis. However, the coordination does not persist during the whole recovery stage of PHZ-induced anemia; instead, Nrf2/miR-144/451 double-KO mice follow a recovery pattern similar to miR-144/451 single-KO mice during the remaining period of erythropoiesis. Third, the complete recovery from PHZ-induced acute anemia in miR-144/451 KO mice takes longer than in Nrf2 KO mice. Our findings demonstrate that complicated crosstalk between miR-144/451 and Nrf2 does exist and the crosstalk of these two antioxidant systems is development-stage-dependent. Our findings also demonstrate that miRNA deficiency could result in a more profound defect of erythropoiesis than dysfunctional transcription factors.

Comparison of the 2009 Institute of Medicine and 2021 Chinese guidelines for gestational weight gain: A retrospective population-based cohort study.

OBJECTIVE: To analyze the associations between gestational weight gain (GWG) and perinatal outcomes based on the GWG guidelines of the Chinese Nutrition Society (CNS) and the Institute of Medicine (IOM). METHODS: This was a retrospective study with 9075 low-risk singleton pregnant women. Logistic regression model was used to analyze associations between GWG categories and perinatal outcomes. Sensitivity analyses were performed based on pre-pregnancy body mass index (calculated as weight in kilograms divided by the square of height in meters). RESULTS: Excessive GWG as defined by the two guidelines was associated with a higher risk of adverse perinatal outcomes. Inadequate GWG was associated with higher risks of small for gestational age (adjusted odds ratio [aOR] 1.34, 95% confidence interval [CI] 1.10-1.64) and preterm birth (aOR 1.70, 95% CI 1.22-2.36), but a lower risk of large for gestational age (LGA) (aOR 0.77, 95% CI 0.63-0.95) according to the IOM guidelines. When using the CNS guidelines, inadequate GWG was associated with only a lower risk of preterm birth (aOR 1.80, 95% CI 1.19-2.70). Sensitivity analyses suggested that excessive GWG was associated with a higher risk of LGA in underweight women. CONCLUSIONS: Both guidelines could demonstrate the relationship between GWG and adverse perinatal outcomes. The CNS guidelines were more suitable for the Chinese population with underweight or normal weight before pregnancy, whereas IOM was more suitable for pregnant women with inadequate GWG.

[Clinical analysis of monochorionic-diamniotic twins with genetic discordance].

OBJECTIVE: To explore the genetic etiology of 5 cases of monochorionic-diamniotic (MCDA) with genetic discordance. METHODS: 148 cases of MCDA twins who were diagnosed by amniocentesis at the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region from January 2016 to June 2020 were selected as the study subjects. Relevant clinical data of the pregnant women were collected, and amniotic fluid samples of the twins were collected separately. Chromosomal karyotyping analysis and single nucleotide polymorphism array (SNP array) assay were carried out. RESULTS: The results of chromosomal karyotyping analysis showed that 5 of the MCDA twins had inconsistent chromosome karyotypes, with an incidence of 3.4% (5/148). SNP array assay showed that 3 fetuses were mosaics. CONCLUSION: Genetic discordance occurs among MCDA twins, and prenatal counseling for such cases should be given by doctors with experience in medical genetics and fetal medicine, and personalized clinical management should be recommended.

A new stock market analysis method based on evidential reasoning and hierarchical belief rule base to support investment decision making.

Stock market analysis is helpful for investors to make reasonable decisions and maintain market stability, and it usually involves not only quantitative data but also qualitative information, so the analysis method needs to have the ability to deal with both types of information comprehensively. In addition, due to the inherent risk of stock investment, it is necessary to ensure that the analysis results can be traced and interpreted. To solve the above problems, a stock market analysis method based on evidential reasoning (ER) and hierarchical belief rule base (HBRB) is proposed in this paper. First, an evaluation model is constructed based on expert knowledge and ER to evaluate stock market sentiment. Then, a stock market decision model based on HBRB is constructed to support investment decision making, such as buying and selling stocks and holding positions. Finally, the Shanghai Stock Index from 2010 to 2019 is used as an example to verify the applicability and effectiveness of the proposed stock market analysis method for investment decision support. Experimental research demonstrates that the proposed method can help analyze the stock market comprehensively and support investors to make investment decisions effectively.

Molecular characterisation of Hb Akron [ß52 (D3) Asp→Val] combined with thalassaemia in a Chinese family.

AIMS: Hb Akron (HBB:c.158A>T) is a rare ß-chain variant and many characteristics about its clinical features still remain unclear. In this study, we aimed to explore the molecular and haematological characterisations of previously undescribed states for Hb Akron associated with different forms of thalassaemia. METHODS: Haematology and genetic analysis were performed in 9 members from a Chinese Zhuang ethnic family. RESULTS: Hb Akron in various combinations with ß0-thalassaemia and α0-thalassaemia were identified and characterised. Simple heterozygote for Hb Akron is asymptomatic, while the compound heterozygotes of Hb Akron associated with the ß0-thalassaemia mutation generates a more severe haematological phenotype than Hb Akron or ß0-thalassaemia mutation seen in isolation. The specific peak of Hb Akron appears at Zone D (195-225 s) in the state of heterozygote and compound heterozygote on haemoglobin capillary electrophoresis device, and the reduction of Hb Akron level in heterozygotes is proportional to the degree of α-globin gene deficiency. CONCLUSIONS: We have for the first time described the genetic and haematological characteristics of Hb Akron combined with different thalassaemia mutations, which will provide useful information for genetic counselling and prenatal diagnostic service of this mutation in a population with high prevalence of thalassaemia.

Appropriate whole genome amplification and pathogenic loci detection can improve the accuracy of preimplantation genetic diagnosis for deletional α-thalassemia.

Objective: To improve the accuracy of preimplantation genetic testing (PGT) in deletional α-thalassemia patients. Design: Article. Patients: fifty-two deletional α-thalassemia couples. Interventions: Whole genome amplification (WGA), Next-generation sequencing (NGS) and PCR mutation loci detection. Main outcome measures: WGA, Single nucleotide polymorphism (SNP) and PCR mutation loci detection results; Analysis of embryo chromosome copy number variation (CNV). Results: Multiple Displacement Amplification (MDA) and Multiple Annealing and Looping-Based Amplification Cycles (MALBAC) methods for PGT for deletional α-thalassemia. Blastocyst biopsy samples (n = 253) were obtained from 52 deletional α-thalassemia couples. The results of the comparison of experimental data between groups MALBAC and MDA are as follows: (i) The average allele drop-out (ADO) rate, MALBAC vs. MDA = 2.27% ± 3.57% vs. 0.97% ± 1.4%, P=0.451); (ii) WGA success rate, MALBAC vs. MDA = 98.61% vs. 98.89%, P=0.851; (iii) SNP haplotype success rate, MALBAC vs. MDA = 94.44% vs. 96.68%, P=0.409; (iv) The result of SNP haplotype analysis is consistent with that of Gap-PCR/Sanger sequencing results, MALBAC vs. MDA = 36(36/72, 50%) vs. 151(151/181, 83.43%), P=0; (v) Valid SNP loci, MALBAC vs. MDA = 30 ± 9 vs. 34 ± 10, P=0.02; (vi) The mean CV values, MALBAC vs. MDA = 0.12 ± 0.263 vs. 0.09 ± 0.40, P=0.916; (vii) The average number of raw reads, MALBAC vs. MDA =3244259 ± 999124 vs. 3713146 ± 1028721, P=0; (viii) The coverage of genome (%), MALBAC vs. MDA = 5.02 ± 1.09 vs. 5.55 ± 1.49, P=0.008. Conclusions: Our findings indicate that MDA is superior to MALBAC for PGT of deletional α-thalassemia. Furthermore, SNP haplotype analysis combined with PCR loci detection can improve the accuracy and detection rate of deletional α-thalassemia.

The oocyte cumulus complex regulates mouse sperm migration in the oviduct.

As the time of ovulation draws near, mouse spermatozoa move out of the isthmic reservoir, which is a prerequisite for fertilization. However, the molecular mechanism remains unclear. The present study revealed that mouse cumulus cells of oocytes-cumulus complexes (OCCs) expressed transforming growth factor-ß ligand 1 (TGFB1), whereas ampullary epithelial cells expressed the TGF-ß receptors, TGFBR1 and TGFBR2, and all were upregulated by luteinizing hormone (LH)/human chorionic gonadotropin (hCG). OCCs and TGFB1 increased natriuretic peptide type C (NPPC) expression in cultured ampullae via TGF-ß signaling, and NPPC treatment promoted spermatozoa moving out of the isthmic reservoir of the preovulatory oviducts. Deletion of Tgfb1 in cumulus cells and Tgfbr2 in ampullary epithelial cells blocked OCC-induced NPPC expression and spermatozoa moving out of the isthmic reservoir, resulting in compromised fertilization and fertility. Oocyte-derived paracrine factors were required for promoting cumulus cell expression of TGFB1. Therefore, oocyte-dependent and cumulus cell-derived TGFB1 promotes the expression of NPPC in oviductal ampulla, which is critical for sperm migration in the oviduct and subsequent fertilization.

Construction of a novel electrochemical sensing platform to investigate the effect of temperature on superoxide anions from cells and superoxide dismutase enzyme activity.

It is of great significance to realize the detection of trace amounts of superoxide anions (O2•-) in biological systems due to the connection between the concentration of O2•- and some diseases. Here, we present a novel method to fabricate a non-enzymatic electrochemical sensor for measuring O2•- from biological systems. The sensor was fabricated by nanocomposites (PAMAM-Au) synthesized by using (PAMAM-G4.0) dendrimers as template/stabilizers for gold nanoparticles (AuNPs) growth. Transmission electron microscopy (TEM) investigations indicate that AuNPs were encapsulated in PAMAM with average diameter about 8 nm. The electrochemical technique confirmed that PAMAM-Au possessed extraordinary electrochemical response to superoxide anions. As an analytical and sensing platform, apart from excellent sensitivity, wide liner range (from 3.69 × 10-5 - 37.2 µM), ultra-low detection limit (0.0123 nM), our sensor also presented satisfying performance for monitoring changes of O2•- levels upon different stimuli. Furthermore, we investigated the effect of temperature on superoxide anions released from living cells and enzyme activity through an electrochemical method for the first time. Most importantly, the simulated electrochemical study in vitro further confirmed that temperature has a crucial influence on both the ability of living cells to resist external stimulation and the antioxidant capacity of superoxide dismutase. As expected, the study may provide researchers with potential value for understanding the temperature effects on organisms and the treatment of diseases caused by oxidative stress.

Prenatal diagnosis of type A fetal interrupted aortic arch by four-dimensional echocardiography with HD-flow STIC: A case report.

Interrupted aortic arch (IAA) is a rare complex congenital heart disease characterized by interrupted continuity between ascending aorta and descending aorta. Prenatal diagnosis of IAA by echocardiography is not uncommonly reported despite its rarity. However, employing four-dimensional ultrasound HD-flow imaging and spatiotemporal image correlation (STIC) in diagnosis of this condition has seldom been reported. We report a case of fetal IAA prenatally diagnosed by two-dimensional echocardiography and HD-flow STIC.

Fetal growth velocity references from a Chinese population-based fetal growth study.

BACKGROUND: Fetal growth velocity standards have yet to be established for the Chinese population. This study aimed to establish such standards suitable for the Chinese population. METHODS: We performed a multicenter, population-based longitudinal cohort study including 9075 low-risk singleton pregnant women. Data were collected from the clinical records of 24 hospitals in 18 provinces of China. Demographic characteristics, reproductive history, fetal ultrasound measurements, and perinatal outcome data were collected. The fetal ultrasound measurements included biparietal diameter (BPD), abdominal circumference (AC), head circumference (HC), and femur diaphysis length (FDL). We used linear mixed models with cubic splines to model the trajectory of four ultrasound parameters and estimate fetal weight. Fetal growth velocity was determined by calculating the first derivative of fetal size curves. We also used logistic regression to estimate the association between fetal growth velocities in the bottom 10th percentile and adverse perinatal outcomes. RESULTS: Fetal growth velocity was not consistent over time or among individuals. The estimated fetal weight (EFW) steadily increased beginning at 12 gestational weeks and peaked at 35 gestational weeks. The maximum velocity was 211.71 g/week, and there was a steady decrease in velocity from 35 to 40 gestational weeks. The four ultrasound measurements increased in the early second trimester; BPD and HC peaked at 13 gestational weeks, AC at 14 gestational weeks, and FDL at 15 gestational weeks. BPD and HC also increased from 19 to 24 and 19 to 21 gestational weeks, respectively. EFW velocity in the bottom 10th percentile indicated higher risks of neonatal complications (odds ratio [OR] = 2.23, 95% confidence interval [CI]: 1.79-2.78) and preterm birth < 37 weeks (OR = 3.68, 95% CI: 2.64-5.14). Sensitivity analyses showed that EFW velocity in the bottom 10th percentile was significantly associated with more adverse pregnancy outcomes for appropriate-for-gestational age neonates. CONCLUSIONS: We established fetal growth velocity curves for the Chinese population based on real-world clinical data. Our findings demonstrated that Chinese fetal growth patterns are somewhat different from those of other populations. Fetal growth velocity could provide more information to understand the risk of adverse perinatal outcomes, especially for appropriate-for-gestational age neonates.

Molecular Characterization of α- and ß-Thalassaemia Among Children From 1 to 10 Years of Age in Guangxi, A Multi-Ethnic Region in Southern China.

Background: Thalassemia is one of the most common genetic diseases in southern China. Howerver, population in different regions or different population has their own spectrums of thalassemia. To investigate the prevalence and spectrum features of thalassemia among children in Guangxi. Hematology and genetic analysis were performed on 71,459 children aged 1-10 years in various regions of Guangxi. Results: A total of 11,821 children were diagnoses with thalassemia including 7,615 (10.66%) subjects of α-thalassemia, 3,507 (4.90%) subjects of ß-thalassemia, and 699 (0.98%) cases with both α- and ß-thalassemia. Nine α-thalassemia mutations and 30 genotypes were identified among the α-thalassemia children. The - -SEA and - -SEA/αα were the most frequent mutation and genotype, respectively. One α-thalassemia fusion gene and a rare 2.4 kb deletion both causing α+-thalassemia were identified, respectively. Thirteen ß-thalassemia mutations and 31 genotypes were characterized among the ß-thalassemia children, with the most common mutation CD41-42 (-CTTT) accounting for 46.05% of the ß-mutations. Two rare mutations IVS-II-5 (G>C), and IVS-I-2 (T>C) were firstly identified. Furthermore, 92 genotypes were identified among 699 children with both α- and ß-thalassemia. Conclusions: Our findings highlight the great heterogeneity and the extensive spectrum of thalassemia among children in Guangxi, which provide an available reference for prevention of thalassemia in this area.

BRD4 Inhibition Protects Against Myocardial Ischemia/Reperfusion Injury by Suppressing Inflammation and Oxidative Stress Through the PI3K/AKT Signaling Pathway.

ABSTRACT: This study aims to investigate the effect and the related mechanisms of bromodomain-containing protein 4 (BRD4) inhibition on myocardial ischemia/reperfusion (I/R) injury. In vivo and in vitro myocardial I/R models were constructed. Expression of BRD4 was examined by RT-qPCR and Western blot. I/R injury was evaluated by analyzing cardiac function and the activity of biochemical markers of myocardial injury. Inflammation and oxidative stress were determined by measuring the levels of myeloperoxidase, TNF-α, IL-6, malondialdehyde, and superoxide dismutase. The activation of the PI3K/AKT signaling pathway was tested by the phosphorylation of p85 and AKT. We found BRD4 was significantly increased in the myocardial tissues after myocardial I/R injury. BRD4 inhibition suppressed the indices of cardiac function and the biochemical markers of myocardial injury. I/R-induced inflammation and oxidative stress were suppressed by shBRD4 in vivo and in vitro. In addition, BRD4 inhibition significantly increased the relative protein expression levels of p-p85, p-AKT T308, and p-AKT S473. In conclusion, this study for the first time demonstrated the protective effect of BRD4 inhibition on myocardial I/R injury in vivo and in vitro, and this effect was related to the suppression of inflammation and oxidative stress through the activation of the PI3K/AKT signaling pathway.

Study on the correlation between the ultrasound phenotype and copy number variation of abnormal embryo in spontaneous abortion.

OBJECTIVE: This study aimed to explore the correlation between the ultrasound phenotype and copy number variation (CNV) of abnormal embryos in spontaneous abortion by investigating the abnormal chromosome copy number of embryos at different developmental stages in early spontaneous abortion. METHODS: A total of 539 patients who had early spontaneous abortion in our hospital between 2015 and 2019 were divided into seven groups according to the phenotype of abnormal embryonic development during pregnancy, and the embryonic tissues of the patients were subjected by single nucleotide polymorphism (SNP) microarray. RESULTS: Among 377 cases with abnormal CNV, 295 (78.25%) cases had chromosome trisomy, and 28 (7.43%) cases had a combination of more than two chromosomes. Triploidy, tetraploidy, chromosome microdeletion/duplication, uniparental disomy, and monosomy 45,X were found in 32 (8.48%), five (1.32%), 31 (8.22%), four (1.02%), and eight (2.12%) cases, respectively. Two (0.53%) cases had autosomal chromosome 21 monosomy. Normal karyotype had the highest proportion in the empty sac group; trisomy 16 accounted for the bulk of chromosomes in the normal yolk sac group, complex triploidy occupied the most part in the abnormal yolk sac group, and no remarkable difference in chromosomal abnormality proportion was found between the normal and abnormal yolk sac groups; the most frequent chromosomal anomaly in a group of germ without cardiac activity and germ<5 mm was trisomy 16; triploidy was the most common in the group with 5 mm ≤ germ ≤ 15 mm, whereas the main distribution of chromosome karyotype was normal, followed by trisomy 13 in a group with germ>15 mm. CONCLUSION: Abnormal embryos with different ultrasound phenotypes in early spontaneous abortion have various CNV types and characteristic distribution. Thus, ultrasound combined with SNP array can provide a basis for the etiological analysis of embryos in spontaneous abortion.