[Prenatal diagnosis and clinical outcomes of 297 fetuses with conotruncal defects].

Objective: To analyze the prenatal diagnosis results and pregnancy outcomes of conotruncal defects (CTD) fetuses, and to explore the correlation between the CTD and chromosome diseases. Methods: A total of 297 cases of invasive prenatal diagnosis and chromosome analysis were collected at the Prenatal Diagnosis Center of Guangzhou Women and Children's Medical Center due to CTD from January 1st, 2011 to December 31th, 2019. According to ultrasonic diagnosis, CTD fetuses were divided into 6 subtypes: tetralogy of Fallot (109 cases), pulmonary atresia (30 cases), transposition of the great arteries (77 cases), double outlet right ventricle (53 cases), truncus arteriosus (14 cases) and interrupted aortic arch (14 cases). According to whether they were combined with intracardiac or extracardiac abnormalities, they were divided into simple group (134 cases), combined with other intracardiac abnormalities group (86 cases), combined with extracardiac abnormalities group (20 cases), combined with intracardiac and extracardiac abnormalities group (37 cases) and only combined with ultrasound soft marker group (20 cases), the last 4 groups were referred as non-simple types. The chromosome test results and pregnancy outcomes of each type and group were analyzed retrospectively. Results: Among the 297 CTD fetuses, the chromosome abnormality rate was 17.5% (52/297). There were 21 cases of abnormal chromosome number, 28 cases of pathogenetic copy number variantions and 3 cases of mosaics. All the 19 cases of micropathogenic fragments smaller than 5 Mb were detected by chromosomal microarray analysis (CMA). Among all the subtypes of CTD, the chromosomal abnormality rate of truncus arteriosus was the highest, at 7/14; while the rate of transposition of the great arteries was the lowest, at 5.2% (4/77). There were significant differences in the rate of chromosomal abnormalities between simple and non-simple types [10.4% (14/134) vs 23.3% (38/163); χ²=8.428, P=0.004]. In each group, the chromosomal abnormality rate was the highest in the combined with intracardiac and extracardiac abnormalities group, at 37.8% (14/37), and the lowest in the simple group, at 10.4% (14/134). There was no significant difference in the rate of chromosomal abnormalities in all subtypes of simple group (all P>0.05). Among 112 cases of live birth, 1 case was 22q11.2 microdeletion syndrome, 5 cases of postnatal clinical diagnosis and prenatal ultrasound diagnosis were not completely consistent, 5 cases died after birth. Conclusions: The incidence of chromosomal abnormalities is high in fetuses with CTD. CTD fetuses with concurrent extrapardiac malformations are more likely to incorporate chromosomal abnormalities. CMA technology could be used as a first-line genetic detection method for CTD. After excluding chromosomal abnormalities, most of the children with CTD have good prognosis.

[Prenatal genetic diagnosis of the fetuses with isolated corpus callosum abnormality].

Objective: To explore the application value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in prenatal diagnosis of isolated corpus callosum abnormality (CCA) fetus. Methods: Fetuses diagnosed with isolated CCA by ultrasound and MRI and receiving invasive prenatal diagnosis in Guangzhou Women and Children's Medical Center and Qingyuan People's Hospital from January 2010 to April 2021 were selected. Karyotype analysis and/or CMA [or copy number variation sequencing (CNV-seq)] were performed on all fetal samples, and WES was performed on fetal samples and their parents whose karyotype analysis and/or CMA (or CNV-seq) results were not abnormal. Results: Among 65 fetuses with isolated CCA, 38 cases underwent karyotype analysis, and 3 cases were detected with abnormal karyotypes, with a detection rate of 8% (3/38). A total of 49 fetuses with isolated CCA underwent CMA (or CNV-seq) detection, and 6 cases of pathogenic CNV were detected, the detection rate was 12% (6/49). Among them, the karyotype analysis results were abnormal, and the detection rate of further CMA detection was 1/1. The karyotype results were normal, and the detection rate of further CMA (or CNV-seq) detection was 14% (3/21). The detection rate of CMA as the first-line detection technique was 7% (2/27). A total of 25 fetuses with isolated CCA with negative results of karyotyping and/or CMA were tested by WES, and 9 cases (36%, 9/25) were detected with pathogenic genes. The gradient genetic diagnosis of chromosomal karyotyping, CMA and WES resulted in a definite genetic diagnosis of 26% (17/65) of isolated CCA fetuses. Conclusions: Prenatal genetic diagnosis of isolated CCA fetuses is of great clinical significance. The detection rate of CMA is higher than that of traditional karyotyping. CMA detection could be used as a first-line detection technique for fetuses with isolated CCA. WES could increase the pathogenicity detection rate of fetuses with isolated CCA when karyotype analysis and/or CMA test results are negative.

[Molecular studies on parental origin and cell stage of nondisjunction in sex chromosome aneuploidies].

To study the parental origin and cell stage of nondisjunction in sex chromosome aneuploidies. Retrospectiving and analyzing the results of 385 cases of SCA confirmed by QF-PCR and karyotype analysis in the prenatal diagnosis center of Guangzhou Women and Children Medical Center from January 2015 to December 2020. The types of samples and prenatal diagnosis indications were analyzed. The parental origin and cell stage of nondisjunction in sex chromosome aneuploidies analyzed by comparing the short tandem repeat (STR) peak patterns of samples from fetuses and maternal peripheral blood. The results show that (1) There were 324 cases of nonmosaic SCA, 113 cases (113/324, 34.9%) were 45, XO, 118 cases (118/324, 36.4%) were 47, XXY, 48 cases (48/324, 14.8%) were 47, XXX and 45 cases (45/324, 13.9%) were 47, XYY. 68 (45/324, 60.2%) cases of 45, X were detected in villus samples. The other SCA cases were mainly detected in amniotic fluid samples. There were 61 mosaic SCA samples, 58(58/61, 95.1%) of mosaic SCA samples were mosaic 45, X. (2) The top two indications of 45, X cases are increased nuchal translucency(53/113, 46.9%) and fetal cystic hygroma (41/113, 36.3%), while the most common indication of other types of SCA was high risk of NIPT(170/272, 62.5%). (3) Among 45, X cases, there were 88 cases (88/113, 77.9%) inherit their single X chromosome from their mother and 25 cases (25/119, 22.1%) from their father. In 47, XXY samples, 47 cases (47/118, 39.8%) of chromosome nondisjunction occurred in meiosis stage Ⅰ of oocytes, 51 cases (51/118, 43.2%) occurred in meiosis stage Ⅰ of spermatocytes, and 20 cases (20/118, 16.9%) occurred in meiosis stage Ⅱ of oocytes. Among 47, XXX samples, 29 cases (29/48, 60.4%) of X chromosome nondisjunction occurred in meiosis stage Ⅰof oocytes, 15 cases (15/48, 31.3%) occurred in meiosis stage Ⅱ of oocytes, and 4 cases (4/48, 8.3%) occurred in meiosis stage Ⅱ of spermatocytes. In summary, the cases of 45, X were mainly diagnosed by villous samples for abnormal ultrasound findings. The other cases of SCA were mainly diagnosed by amniocentesis samples for abnormal NIPT results. Different types of SCA, the origin and occurrence period of sex chromosome nondisjunction were different.

[Chorionic villus cell culture and karyotype analysis in 1 983 cases of spontaneous miscarriage].

Objective: To investigate the relationship between spontaneous miscarriage and embryonic chromosome abnormalities, and to evaluate the clinical application of karyotype analysis by chorionic villus cell culture. Methods: The chorionic villus karyotype of 1 983 cases of miscarriage from January 2010 to July 2016 in Guangzhou Women and Children's Mecical Center were analyzed retrospectively. The miscarried chorionic villi were obtained by curettage under sterilized condition. The chromosome specimens were prepared after chorionic villus cell culture. Karyotype analysis was performed by G-banding technique. Results: In the 1 983 samples, successful karyotype analysis was performed in 1 770 cases, with the successful rate of 89.98%. Chromosomal abnormalities were found in 1 038 cases (58.64%, 1 038/1 770). Chromosomal structural abnormalities were found in 37 cases. The numeral abnormalities were more common than structural abnormalities, and most of the numeral abnormalities were aneupoidies. In turn, they were trisomy 16, 45,X, trisomy 22, trisomy 2, trisomy 21, trisomy 15. The most common structural abnormality was balanced translocation, including Robersonian translocation. Female embryoes accounted for 61.02% (1 080/1 770) miscarriages and for 57.4%(596/1 770) of chromosomal abnormalities, while male embroyes acoounted for 61.02% (1 080/1 770) , 57.4% (596/1 770) respectively. The proportion of female embryoes was higher than male embryoes. The median age of the patients was 30 years old (16-46 years old) . As the maternal age increased, the proportion chromosomal abnormalities increased. The incidence of chromosomal abnormalities in the advanced age group (≥35 years) was 68.38% (240/351) , which was significantly higher than that in the younger group (56.24%, 798/1 419; χ(2)=17.10, P<0.01). Conclusions: Embryonic chromosomal abnormalities are the most common cause of early spontaneous miscarriage. The abnormalities centralize in some karyotypes. There is certain relationship between maternal age and the incidence of miscarriage, as well as the embryonic gender. Chorionic villus cell culture and karyotype analysis are helpful in finding the cause of miscarriage and counsel the patients.

Prenatal diagnosis of sex chromosome aneuploidies: experience at a mainland Chinese hospital.

The aim of this study is to assess the initial indications, frequency and termination rates of pregnancies with sex chromosome aneuploidies (SCAs), at a mainland Chinese hospital. A total of 56 cases (0.9%) with SCAs were identified in 6,515 pregnancies referred for fetal karyotyping. Turner syndrome was the most commonly diagnosed SCA in prenatal diagnosis (48.2%). The most common referral reason for pregnancies with Turner syndrome was cystic hygroma on ultrasonography. The main reasons for fetal karyotyping in other types of SCAs were a positive prenatal screening test and advanced maternal age. A total of 47 (84%) of the pregnancies with SCAs were terminated and nine (16%) continued. This study first reported the rate of SCAs detected at prenatal diagnosis and the outcomes of these pregnancies in mainland China, and showed a very high termination rate for pregnancies with SCAs.

Hypothalamic control of energy metabolism via the autonomic nervous system.

The hypothalamic control of hepatic glucose production is an evident aspect of energy homeostasis. In addition to the control of glucose metabolism by the circadian timing system, the hypothalamus also serves as a key relay center for (humoral) feedback information from the periphery, with the important role for hypothalamic leptin receptors as a striking example. The hypothalamic biological clock uses its projections to the preautonomic hypothalamic neurons to control the daily rhythms in plasma glucose concentration, glucose uptake, and insulin sensitivity. Euglycemic, hyperinsulinemic clamp experiments combined with either sympathetic-, parasympathetic-, or sham-denervations of the autonomic input to the liver have further delineated the hypothalamic pathways that mediate the control of the circadian timing system over glucose metabolism. In addition, these experiments clearly showed both that next to the biological clock peripheral hormones may "use" the preautonomic neurons in the hypothalamus to affect hepatic glucose metabolism, and that similar pathways may be involved in the control of lipid metabolism in liver and white adipose tissue.

[Reconstruction of the hand with thin skin flap with preserved subdermal vascular rete].

Since Dec. 1991, we have used thin skin flaps to reconstruct hand with scar contractures of hand as a result of burn or trauma in 10 patients, including one with osteomyelitis of the proximal phalanx. The size of the skin flaps ranged from 8-18 x 4 x 7 cm. The shortest time of division of the pedicle was 7 days and the longest was 12 days, with a mean of 8. 7 days. The thin skin flap with preserved subdermal vascular rete was compared with free skin graft, also with preserved subdermal vascular rete, and conventional skin flap, and its advantages and shortcomings were discussed. The mechanism of survival after an early division of the pedicle was also discussed.

[The evaluation of complications following augmentation rhinoplasty with silicon gel].

Since 1985, 15 patients who suffered from complications after augmentation rhinoplasty by injection of silicone gel have been reoperated on in our department. These complications included: (1) unsatisfactory aesthetic result in nine cases; (2) ulceration in three cases; (3) ophthalmic complications, including blindness of one-eye (2 cases) and two-eyes with severe vision disorders (1 case). The reasons for unsatisfactory aesthetic result and other complications were analysed and evaluated.

Iron carrier proteins facilitate engraftment of allogeneic bone marrow and enduring hemopoietic chimerism in the lethally irradiated host.

Cell-free supernatants of rabbit bone marrow were fractionated, separated, and purified by Ultrogel and Superose chromatography. A single fraction promoted engraftment of allogeneic bone marrow and enduring hemopoietic chimerism across the H-2 barrier in lethally irradiated mice. This "bio-active" fraction, analyzed by reducing SDS-PAGE electrophoresis, and transblotted on PVDF membrane, and purified by reverse-phase HPLC and SDS-PAGE electrophoresis yielded a main prealbumin band that when examined for primary structure by Edman degradation, proved to be rabbit transferrin. This was also attested by highly specific precipitation of the prealbumin band with polyclonal antibodies to rabbit transferrin. Iron-saturated human transferrin, lactotransferrin, and egg transferrin (conalbumin) were assayed in irradiated C57BL/6 mice infused with bone marrow from histoincompatible BALB/c donors. Mice treated with iron-loaded transferrins survive and develop enduring allogeneic chimerism with no discernible signs of graft-versus-host disease. Iron carrier proteins thus provide an unique means of achieving successful engraftment of allogeneic bone marrow in immunologically hostile murine H-2 combinations.