OBJECTIVE: To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes. METHODS: Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed. RESULTS: The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c.603T>G (p.1201M) and TGFB3 c.536delA (p.H179FS35) had not been reported previously. CONCLUSION Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.
Humans ; Loeys-Dietz Syndrome/genetics* ; Receptor, Transforming Growth Factor-beta Type I/genetics* ; Receptor, Transforming Growth Factor-beta Type II/genetics* ; Transforming Growth Factor beta3 ; Face

Objective:To investigate the genetic etiology of fetal conotruncal heart defects (CTDs) and to evaluate the performance of copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) in identifying the genetic etiology.Methods:This retrospective study involved 196 fetuses diagnosed with CTDs by fetal echocardiography in Beijing Anzhen Hospital, Capital Medical University from June 2017 to December 2021. CNV-seq was performed to screen for chromosomal abnormalities [aneuploidy and copy number variations (CNVs)] in the fetuses and their parents, and then WES was performed if CNV-seq was negative. The diagnostic yields of genetic abnormalities [aneuploidy+CNVs+single nucleotide variations (SNVs)] for different types of CTDs were compared using Chi-square test. Results:CNV-seq revealed 54 cases (27.6%, 54/196) with chromosomal abnormalities, including 14 (7.1%, 14/196) aneuploidies, 39 (19.9%, 39/196) CNVs and one aneuploidy complicated by CNVs. Together with another 13 fetuses with pathogenic or likely pathogenic SNVs detected by WES among the rest 142 cases whose CNV-seq results were negative, the total detection rate of genetic abnormalities was 34.2% (67/196). WES increased the diagnostic yield for CTDs by 9.2% (13/142). There was significant difference in the diagnostic yields for different types of CTDs ( χ2=20.31, P=0.002). The diagnostic yield was relatively high for interrupted aortic arch of type B, absent of the pulmonary valve -type of tetralogy of Fallot (9/10 and 8/12), but low for transposition of the great arteries (12.5%, 5/40). Conclusions:CNVs are the common genetic abnormalities in fetal CTDs, and SNVs are also detected in some cases. It is recommended that all fetuses with CTDs should undergo genetic testing. CNV-seq should be used in combination with WES if possible to improve the identification of genetic etiology and provide reference for genetic counseling.

Methcathinone (MCAT) belongs to the designer drugs called synthetic cathinones, which are abused worldwide for recreational purposes. It has strong stimulant effects, including enhanced euphoria, sensation, alertness, and empathy. However, little is known about how MCAT modulates neuronal activity in vivo. Here, we evaluated the effect of MCAT on neuronal activity with a series of functional approaches. C-Fos immunostaining showed that MCAT increased the number of activated neurons by 6-fold, especially in sensory and motor cortices, striatum, and midbrain motor nuclei. In vivo single-unit recording and two-photon Ca²⁺ imaging revealed that a large proportion of neurons increased spiking activity upon MCAT administration. Notably, MCAT induced a strong de-correlation of population activity and increased trial-to-trial reliability, specifically during a natural movie stimulus. It improved the information-processing efficiency by enhancing the single-neuron coding capacity, suggesting a cortical network mechanism of the enhanced perception produced by psychoactive stimulants.
Mice ; Animals ; Reproducibility of Results ; Neurons ; Sensation ; Perception

Objective:To summarize the etiological mechanism, echocardiographic and clinical features of fetal cardiomyopathies (FCMs).Methods:According to the data of echocardiography in Maternal-Fetal Medicine Center in Fetal Heart Disease of Beijing Anzhen Hospital during 2015 January to 2020 December, 70 cases with FCMs were retrospectively reviewed, and the clinical, ultrasonic, pathological and clinical outcome data were collected. Whole exome sequencing and whole genome sequencing were used to identify the genetic changes.Results:Primary FCMs were diagnosed in 55 cases (78.6%, 55/70), including 39 fetuses with non-compaction of the ventricular myocardium (NVM), 10 with dilated cardiomyopathy (DCM), 5 with hypertrophic cardiomyopathy (HCM), and 1 with restricted cardiomyopathy (RCM). Secondary FCMs were diagnosed in 15 cases (21.4%, 15/70), including 7 fetuses with maternal anti-Ro/La antibodies (presenting with DCM), 4 with twin-twin transfusion syndrome (2 with DCM and 2 with HCM), 2 with fetal anemia (presenting with DCM), 1 with maternal diabetes (presenting with HCM) and 1 with chorioangioma of the placenta (presenting with DCM). In all cases, 9 cases were born, 3 cases died in perinatal period, and 58 pregnancies were terminated due to ineffective treatment or the decisions of pregnant women. Thirty cases with primary FCMs were performed with genetic tests, and 13 of them were identified with positive genetic changes related to FCMs, including 12 cases with NVM and 1 with HCM.Conclusions:Primary FCMs are more common than secondary FCMs in fetal period. The genetic disorders have a high proportion in fetal NVM. Fetal DCM and HCM have a large spectrum of intrinsic and extrinsic causes.

Objective:To investigate the differences of umbilical vein diameter(D), time average peak velocity(TAmax) and blood flow between congenital heart disease and normal fetus.Methods:The umbilical vein diameter and time average peak velocity of 69 fetuses with congenital heart disease (disease group) from 22 to 27 weeks were prospectively studied in Maternal-Fetal Medical Center in Fetal Heart Disease of Beijing Anzhen Hospital from May 2021 to September 2021. Q 1 (umbilical venous blood flow) was calculated according to the formular [Q=0.5TAmax·π·(D/2) 2)], and Q 2 (Q 2=Q 1/weight) was calculated according to the fetal weight. At the same time, 111 normal fetuses with matched gestational age were selected as control group. The differences of fetal umbilical vein D, TAmax, Q 1 and Q 2 between the two groups were analyzed. Results:The inner diameter of umbilical vein D, TAmax, Q 1 and Q 2 in the congenital heart disease group were lower than those in the control group(all P<0.05). In the control group, the inner diameter of umbilical vein D, TAmax and Q 1 increased with the increase of gestational age and showed a positive linear correlation( r=0.608, 0.320, 0.626; all P≤0.001), while there was no obvious linear correlation between Q 2 and gestational age( r=0.189, P=0.047). Conclusions:The decrease of umbilical vein D, TAmax, Q 1 and Q 2 in the fetus with congenital heart disease indicates the decrease of effective blood flow in placenta-fetus circulation, which indirectly reflects the decrease of placental function in the fetus with congenital heart disease.

Objective:Through the establishment and application of the biosafety autopsy pathology platform in Huoshenshan Hospital, the feasibility and application effect of the biosafety autopsy pathology platform were analyzed.Methods:The feasibility and application effect of the biosafety autopsy pathology platform were analyzed by layout design, instruments and equipment preparation, testing methods examination, and effect evaluation.Results:A total number of 26 cases of systematic autopsy and 8 cases of minimally invasive autopsy (puncture) were performed on the biosafety autopsy pathology platform, and no one was infected. Some pathology original findings were identified, including COVID-19 and pathological characteristics of identification, SARS respiratory failure mechanism and treatment significance, systemic distribution and spreading mechanism of the new coronavirus, the " storm" of inflammation pathological basis, some tumor markers rise in pulmonary pathological cell source and the overcast with fibrosis characteristics, such findings play important roles in the clinical diagnosis and treatment of COVID-19.Conclusions:The study of autopsy pathology is of great significance for the prevention and control of emerging infectious disease, which calls for early intervention. To promote the standard construction of biosafety autopsy platform is the key to the pathological study of emerging infectious diseases. Pathological research and clinical diagnosis and treatment should be combined to inform each other.

Objective:To evaluate the heart hemodynamics in fetuses with premature ductus arteriosus constriction or closure using fetal heart quantification (FHQ).Methods:The clinical data of 50 singleton fetuses with ductus arteriosus constriction ( n=35) or ductus arteriosus closure ( n=15) who underwent echocardiography in Department of Ultrasound, Beijing Anzhen Hospital were retrospectively analyzed, from May 2013 to January 2020. Fifty healthy singleton fetuses were randomly selected as the control group. The ductus arteriosus diameter (DA), pulsatility index (PI), diameter of the left atrium(LA) and right atrium(RA), diameter of the left ventricle (LV) and right ventricle (RV), tricuspid regurgitation/right atrium area ratio (TR/RA Ratio), pressure gradient of tricuspid regurgitation (PG of TR), and heart/chest ratio were measured using conventional fetal echocardiography; the correlations among the parameters were analyzed. Speckle-tracking analysis was used to analysis and compute the LV and RV global spherical index (GSI), fractional area change (FAC) and global strain (GS), the LV ejection fraction(EF) and stroke volume (SV). These variables and their correlations were compared and analyzed. Results:Compared with the control group, the GS and FAC of the LV and RV in the ductus arteriosus constriction or closure groups were lower ( P<0.05) while the LV-SV was higher ( P<0.05). The FAC, GS, and EF values of the LV were higher in the premature ductus arteriosus closure group than in the ductus arteriosus constriction group ( P<0.05), while the RV-FAC was lower ( P<0.05), the RV-GS and LV-SV showed no significant changes ( P>0.05). Correlation analyse showed that the PI was positively correlated with DA( r=0.364, P<0.05); the PG of TR was negatively correlated with DA( r=-0.414, P<0.05); the TR/RA Ratio was negatively linearly correlated with PI( r=-0.388, P<0.05), and positively correlated with RV/LV Ratio ( r=0.369, P<0.05); the other parameters were not significantly correlated with the DA or PI ( P>0.05). Conclusions:Fetal heart hemodynamics in the premature ductus arteriosus constriction or closure groups change significantly, FHQ can provide valuable information for the evaluation of the fetal heart with ductus arteriosus constriction or closure.

Objective:To explore the changes of biparietal diameter, head circumference and cerebrovascular hemodynamics in fetuses with hypoplastic left heart syndrome (HLHS) during middle pregnancy.Methods:The biparietal diameter, head circumference, middle cerebral artery pulsatility index (MCA-PI), umbilical artery pulsatility index (UA-PI) and MCA-PI/UA-PI (CPR) of 41 fetuses with HLHS(HLHS group) were retrospectively analyzed from January 2015 to December 2019 in Beijing Anzhen Hospital, and were compared with those of 82 normal fetuses matched for gestational age at the same period (control group).Results:The Z-scores of head circumference, MCA-PI and CPR in with HLHS group were lower than in control group(all P<0.05); Head circumference in HLHS group were weakly and positively correlated with the MCA-PI and CPR ( r=0.385, 0.416; all P<0.05). Conclusions:There are some changes in the head circumference and cerebral hemodynamics in fetuses with HLHS during mid-gestational age, and the head circumference is weakly and positively correlated with MCA-PI and CPR, which has clinical significance.

Objective:To investigate the value of artificial intelligence in screening normal or abnormal four-chamber view of the fetal heart.Methods:Selecting 3 996 pictures of normal and abnormal end systolic four chamber views and 450 video clips from the database of Beijing Key Laboratory of Fetal Heart Disease Maternal and Fetal Medicine Research in Beijing Anzhen Hospital as training set, test set and verification set to train, test and verify DGACNN model. ①Comparing DGACNN, DGACNN-ALOCC and other classification models(Densenet, Resnet50, InceptionV3, InceptionResnetV2) to detect the model with the most advanced level by recognizing 200 normal pictures and 200 abnormal pictures. ②Fetal echocardiographers were divided into three groups according to their experiences: primary, intermediate and advanced, 3 doctors in each group, and comparing the average score between each group or three groups and DGACNN by recognizing 100 normal pictures and 100 abnormal pictures.Results:①When the the false positive rate(FPR) was in the range of 20%, the recognition accuracy of DGACNN was the highest with 0.850, the recognition accuracy of other models were DGACNN-ALOCC 0.835, Densenet 0.780, Resnet50 0.700, InceptionV3 0.670, InceptionResnetV2 0.650, respectively. ②When FPR was in the range of 20%, the area under ROC curve of DGACNN was the largest with 0.881, the area under ROC curve of other models were DGACNN-ALOCC 0.864, Densenet 0.850, Resnet50 0.822, Inceptionv3 0.779, InceptionResnetV2 0.703, respectively. ③When the FPR was in the range of 20%, the average recognition accuracy of the senior fetal echocardiographer group was the highest with 0.863, followed by DGACNN 0.840, which was higher than the average recognition accuracy of the primary and intermediate groups with 0.760, 0.807; the average recognition accuracy of DGACNN was higher than the total average recognition accuracy of the primary, intermediate and advanced groups with 0.810.Conclusions:Artificial intelligence is accessible in screening four chamber view of fetal echocardiography, with high recognition accuracy.

Objective:To investigate the value of post left atrium space index (PLASI) in the diagnosis of fetal isolated total anomalous pulmonary venous connection (TAPVC).Methods:Twenty-six cases of fetal isolated TAPVC were retrospectively analyzed as the TAPVC group and 243 normal fetuses were selected as the control group from October 2012 to April 2019 in the Consultation Center of Maternal-Fetus Medicine in Fetal Heart Disease in Beijing An Zhen Hospital. The width of the PLAS and the diameter of the descending aorta were measured in the four chamber view, and then the PLAS index (PLASI) (the width of the PLAS/the diameter of the descending aorta) was calculated. The relationships between the width of PLAS, the diameter of descending aorta and the PLASI and gestational age were analyzed. The difference of the PLASI between isolated TAPVC group and control group was analyzed, and ROC curve was used to analyze the sensitivity and specificity in identifying the isolated TAPVC fetuses and normal fetuses.Results:In the 243 normal fetuses in control group, both the width of the PLAS and the diameter of the descending aorta increased with gestational age ( r s=0.362, 0.648, P<0.05). There was no statistically significant correlation between the PLASI and gestational age ( r s=-0.065, P>0.05). The PLAS and the PLASI in isolated TAPVC group were all significantly higher than those in control group ( t=26.31, 34.90, P<0.01). Based on the ROC curve analysis, when the cutoff value was set to 3.6 mm, the sensitivity and specificity of PLAS in identifying isolated TAPVC and normal fetuses were 97.5% and 100%, respectively. When the cutoff value was set to 1.1, the sensitivity and specificity of PLASI in identifying isolated TAPVC and normal fetuses were 100% and 100%, respectively. Conclusions:The PLASI is a sensitive parameter in identifying the isolated TAPVC, which is helpful for the rapid screening of the isolated TAPVC.