First-Trimester Echocardiographic Features and Perinatal Outcomes in Fetuses With Congenital Absence of the Aortic Valve.

OBJECTIVES: The purpose of this study was to describe the echocardiographic features and perinatal outcomes of congenital absence of the aortic valve diagnosed by first-trimester echocardiography. METHODS: This retrospective study assessed the feasibility of first-trimester echocardiography in detecting absence of the aortic valve. All cases of absence of the aortic valve diagnosed by first-trimester fetal echocardiography from January 2010 to December 2014 were identified at a single referral center using an established perinatal database. Demographic information, echocardiograms, perinatal outcomes, and autopsy reports were reviewed. Echocardiographic features were described. RESULTS: A total of 50,822 fetuses underwent first-trimester echocardiography during the study period. Ten cases of congenital absence of the aortic valve were diagnosed, for an overall incidence rate of 0.019%. The earliest gestational age at diagnosis was 11 weeks 6 days. The mean crown-lump length was 61.9 mm; mean gestational age was 12 weeks; and mean maternal body mass index ± SD was 21.2 ± 3.9 kg/m(2). Nine fetuses had increased nuchal translucency ranging from 2.4 to 12.4 mm (mean ± SD, 6.4 ± 3.6 mm). Color Doppler flow imaging revealed biphasic bidirectional flow in the ascending aorta and aortic arch and reversed flow in the ductus venosus during atrial systole in all cases. Reversed diastolic flow was present in the umbilical arteries and thoracic aorta. All cases had complex cardiac malformations as well as extracardiac abnormalities. CONCLUSIONS: Our study confirms that absence of the aortic valve is a rare cardiac defect that can be diagnosed by first-trimester fetal echocardiography. A "to-and-fro" flow pattern or biphasic bidirectional flow in the great arteries is a key echocardiographic feature in fetuses with absence of the aortic valve.

Routine screening for fetal limb abnormalities in the first trimester.

OBJECTIVE: We aim to determine the accuracy of first-trimester ultrasonography in detecting fetal limb abnormalities. METHODS: This is a retrospective study of all women undergoing fetal nuchal translucency (NT) assessment and detailed fetal anatomic survey in the first trimester at a single tertiary-care referral center in China. Fetal anatomy scans were repeated in the second trimester. Detection of fetal limb abnormalities was compared between first and second trimester anatomy scans and confirmed at delivery or at autopsy. RESULTS: Analyzed were 9438 fetuses from 9197 women (241 twin pairs). The incidence of fetal limb abnormalities was 0.38% (36/9438). Of these, 28 (77.8%) were diagnosed prenatally: 23 (63.9%) on first trimester scan and 5 (13.9%) on second trimester scan. Limb reduction defects (usually transverse limb deficiencies) were the most common limb defects identified in the first trimester (n = 12), followed by clubfoot (n = 4), skeletal dysplasia (n = 3), sirenomelia (n = 1), limb dysplasia (n = 1), malposition (n = 1), and syndactyly (n = 1). Nine fetuses with isolated limb abnormalities had normal NT, while 74.1% (20/27) of limb abnormalities that were associated with other abnormalities had increased NT. CONCLUSIONS: This study demonstrates that the majority of limb abnormalities detected prenatally [23/28 (82%)] can be identified in the first trimester, especially major limb defects; however, our numbers are small and still need larger cases for further investigation.

Tetraspanin CD9 is involved in pancreatic damage during caerulein-induced acute pancreatitis in mice.

OBJECTIVE: Pancreatic acinar cell necrosis and subsequent inflammatory response aggravate acute pancreatitis (AP). Tetraspanin CD9 has been reported to mediate inflammatory signaling by regulating molecular organization at the cell surface. This study aimed to investigate the role of CD9 in caerulein-induced AP (CIP) in mice. METHODS: The expression of CD9 was detected in CIP in mice in vivo and cholecystokinin (CCK)/recombinant mouse tumor necrosis factor (rmTNF)-α induced pancreatic acinar cell death in vitro by quantitative real-time polymerase chain reaction, Western blot and immunofluorescence. The roles of CD9 in pancreatic acinar cell death and inflammatory response were further studied through the deletion of CD9 expression using small interfering RNA (siRNA). RESULTS: CD9 was markedly upregulated in pancreatic tissues in mice during the early onset of CIP and was located mainly at the pancreatic acinar cell surface, which was associated with pancreatic damage. Additionally, incubation with CCK or rmTNF-α directly increased the expression of CD9 in isolated mice pancreatic acinar cells in vitro. The deletion of CD9 expression partially reversed both pancreatic acinar cell death induced by CCK and mRNA levels of proinflammatory cytokines produced by damaged acinar cells. CONCLUSION: These results indicate that increased CD9 expression may be involved in pancreatic injury, possibly via the promotion of cytokine expressions in CIP in mice.

Prognostic significance of annexin A1 expression in pancreatic ductal adenocarcinoma.

Annexin A1 is a 37-kDa calcium- and phospholipid-binding protein of the annexin superfamily considered to play an important role in tumorigenesis. However, associations with clinicopathological features in pancreatic ductal adenocarcinoma (PDAC) cases have yet to be fully defined. We therefore investigated the prognostic value of annexin A1 protein as a PDAC biomarker in 83 tumor and matched non-cancerous tissues or normal pancreas tissues. Expression was analyzed using real-time RT-PCR, Western blotting and immunohistochemistry. In non-tumor tissue, myoepithelial cells showed no or weak expression of annexin A1 while expression was strong and sometimes even located in the nuclei of endothelial cells in tumor tissue. High expression was significantly associated with advanced stage (P <0.05) and a worse overall survival (P <0.05). These results provide new insights to better understand the role of annexin A1 in PDAC survival, and might be relevant to prediction of prognosis and development of more effective therapeutic strategies aimed at improving survival.

[Perinatal management and outcome of different types of fetal arrhythmia].

OBJECTIVE: To evaluate the perinatal management and outcome of different types of fetal arrhythmia. METHODS: A retrospective analysis was conducted among the fetuses with arrhythmia identified by M-mode and pulsed Doppler echocardiography in a single institution between October 2003 and December 2010. RESULTS: A total of 130 fetuses were found to have fetal arrhythmia. The most common arrhythmia during pregnancy was extrasystole (n=59), followed by bradycardia (n=23), tachycardia (n=16), atrial flutter (AF, n=3), atrioventricular block (AVB, n=12) and other arrhythmia (n=17). The overall incidence of cardiac anomalies (commonly fetal bradycardia) was 9.2% in these cases. The prognosis of arrhythmia differed significantly between cases of different classifications. The type of fetal arrhythmia (P=0.024), presence of congenital heart defect (CHD, P=0.000) and fetal hydrops (P=0.008) were significant risk factors associated with termination of pregnancy. CONCLUSION: Fetal arrhythmias without CHD or hydrops under close monitoring often have good clinical outcome, while fetal bradycardia is associated with a high mortality rate. CHD and the presence of fetal hydrops are significant risk factors for pregnancy termination.

Prenatal diagnosis of unilateral pulmonary dysplasia.

Pulmonary hypoplasia is a rare congenital disorder; most cases occur in association with other congenital abnormalities, including congenital diaphragmatic hernia, oligohydramnios, and/or skeletal deformities. The authors report a case of unilateral pulmonary hypoplasia diagnosed prenatally and confirmed at autopsy.

[Genetic variation and association of prostaglandin F2alpha receptor (PTGFR) gene with sow maternal behaviors in a White Duroc x Erhualian resource population].

Maternal behaviors of sows around parturition are important for survival of newborn offspring. Failure to establish normal maternal bonds such as maternal infanticide and crushing often occurs in some individuals. It causes both significant economic losses to the pig industry and severe problems of piglet welfare. Prostaglandin F2-alpha not only can stimulate the nest-building behavior of sows before parturition but also plays an important role in reproductive process and maternal behavior through protein FP encoded by the prostaglandin F receptor gene (PTGFR) as its receptor. In this study, genetic variation and association study of PTGFR gene with nest-building behavior, maternal infanticide, and crushing behavior was carried out in a White Duroc x Erhualian resource population. As a result, five synonymous mutations were identified on exon 1 and exon 2. Exon 1 g .250 A>G, Exon 1 g.619 G>A and Exon 2 g.483 T>C were chosen for genotyping in individuals of F0, F1 and 289 F2 sows. Family-based transmission disequilibrium test (TDT) demonstrated that there were no significant associations of 3 SNPs and haplotypes of PTGFR gene with sow nest-building, maternal infanticide and crushing behavior (P > 0.05). Therefore, it can be concluded that PTGFR gene is not the causative candidate gene for sow maternal behaviors.

[Analysis of 993 cases of fetal malformations from 1999 to 2006].

OBJECTIVE: To study the value of prenatal ultrasound in the diagnosis of fetal malformations. METHODS: We retrospectively analyzed the clinical data of 993 cases of neonates and induced babies with malformations who were labored in our hospital from January 1999 to October 2006. RESULTS: The incidence rate of fetal malformation was 22.5 per thousand in our study group. The detection rate of prenatal ultrasound was 79.02% (1 062/1 344), among which the detection rate of the severe malformations (87.58%, 860/982) were significantly higher than that of the minor malformations (55.80%, 202/362) (P < 0.005). The false negative rate was high for the extremity malformations (39.46%) and facial malformations (31.91%), especially the acrosclerodermas, simple cleft palates, and ear deformities. CONCLUSION: Prenatal ultrasound is sensitive for fetal severe malformations, while the detection rate is low for fetal minor malformations.

Quantitative structure-selectivity relationship for M2 selectivity between M1 and M2 of piperidinyl piperidine derivatives as muscarinic antagonists.

Muscarinic M2 receptor antagonists with high subtype selectivity (M2/M1) will decrease the toxicity in central nervous system in treatment of AD. The exploration of quantitative structure-selectivity relationship (QSSR) to muscarinic M2 receptor antagonists will provide design information for drug with fewer side effects. In this paper, CoMFA models of pK(i)(M1), pK(i)(M2) and p[K(i)(M2)/K(i)(M1)] (pK(i)(M2)-pK(i)(M1)) were used to study the subtype selectivity (M2/M1) of piperidinyl piperidine derivatives as muscarinic M2 subtype receptor antagonists. The parameters of the three models are: 0.633, 0.636 and 0.726 for cross-validated r(2) (r(cv)(2)), 0.109, 0.204 and 0.09 for the Standard error of estimate (SD), respectively. The results show the model of p[K(i)(M2)/K(i)(M1)] is the best one for design of piperidinyl piperidine derivatives as muscarinic antagonists with high subtype selectivity (M2/M1).

Genetic variations of the porcine PRKAG3 gene in Chinese indigenous pig breeds.

Four missense substitutions (T30N, G52S, V199I and R200Q) in the porcine PRKAG3 gene were considered as the likely candidate loci affecting meat quality. In this study, the R200Q substitution was investigated in a sample of 62 individuals from Hampshire, Chinese Min and Erhualian pigs, and the genetic variations of T30N, G52S and V199I substitutions were detected in 1505 individuals from 21 Chinese indigenous breeds, 5 Western commercial pig breeds, and the wild pig. Allele 200R was fixed in Chinese Min and Erhualian pigs. Haplotypes II-QQ and IV-QQ were not observed in the Hampshire population, supporting the hypothesis that allele 200Q is tightly linked with allele 199V. Significant differences in allele frequencies of the three substitutions (T30N, G52S and V199I) between Chinese indigenous pigs and Western commercial pigs were observed. Obvious high frequencies of the "favorable" alleles 30T and 52G in terms of meat quality were detected in Chinese indigenous pigs, which are well known for high meat quality. However, the frequency of the "favorable" allele 199I, which was reported to have a greater effect on meat quality in comparison with 30T and 52G, was very low in all of the Chinese indigenous pigs except for the Min pig. The reasons accounting for this discrepancy remain to be addressed. The presence of the three substitutions in purebred Chinese Tibetan pigs indicates that the three substitutions were ancestral mutations. A novel A/G substitution at position 51 in exon 1 was identified. The results suggest that further studies are required to investigate the associations of these substitutions in the PRKAG3 gene with meat quality of Chinese indigenous pigs, and to uncover other polymorphisms in the PRKAG3 gene with potential effects on meat quality in Chinese indigenous pigs.

Ultrasonographic evaluation of fetal facial anatomy (I): ultrasonographic features of normal fetal face in vitro study.

BACKGROUND: Because of lacking skills in scanning the normal fetal facial structures and their corresponding ultrasonic features, misdiagnoses frequently occur. Therefore, we studied the appearance features and improved displaying skills of fetal facial anatomy in order to provide basis for prenatal diagnosis. METHODS: Twenty fetuses with normal facial anatomy from induced labor because of other malformations except facial anomalies were immersed in a water bath and then scanned ultrasonographically on coronal, sagittal and transverse planes to define the ultrasonic image features of normal anatomy. The coronal and sagittal planes obtained from the submandibular triangle were used for displaying the soft and hard palate in particular. RESULTS: Facial anatomic structures of the fetus can be clearly displayed through the three routine orthogonal planes. However, the soft and hard palate can be displayed on the planes obtained from the submandibular triangle only. CONCLUSIONS: The superficial soft tissues and deep bony structures of the fetal face can be recognized and evaluated by routine ultrasonographic images, which is a reliable prenatal diagnostic technique to evaluate the fetal facial anatomy. The soft and hard palate can be well demonstrated by the submandibular triangle approach.

Research on the genetic variations of a1-fucosytransferase (FUT1) gene in 26 pig breeds.

Enterotoxigenic Escherichia coli F18(ECF18) is a main pathogen that causes edema disease and post-weaning diarrhoea in piglets, and al-fucosytransferase (FUT1) gene has been identified as a candidate gene for controlling the expression of the receptor for ECF18 bacteria. The genetic variations at position 307 nucleotide in open reading frame of FUT1 gene in 26 pig breeds (total 1458 individuals) from 5 western commercial pig breeds and 21 Chinese native pig breeds were investigated by PCR-RFLP. The results showed that the genetic polymorphisms of the FUT1 locus were only detected in 5 western pig breeds and the Chinese Lingao pig breed, 5 western pig breeds possessed 3 different genotypes, and Lingao pig breed had two susceptible genotypes GG and AG, while all the other 20 Chinese native pig breeds only presented the susceptible genotype GG. The results indicated that if M307G-A point mutation in the coding region of FUT1 gene was the key factor determining the expression of the ECF18 receptor, most of Chinese native pig breeds were absent of the genetic background on the resistance to ECF18 bacteria. In this case, it was inferred that the resistance gene to ECF18 might be originated from western pig breeds. In addition, it is of great importance for the conservation of Lingao pig breed as it is the only found Chinese native pig breed possessing resistance M307A allele in FUT1 gene. Generally, compared with exotic pig breeds, Chinese native pig breeds have stronger resistance to edema disease and post-weaning diarrhoea in piglets. The results suggested that further study should be done to identify and characterize putative QTL (quantitative trait locus) or/and the functional gene responsible for the resistance to ECF18 in Chinese native pig breeds.

[Prenatal ultrasonographic evaluation of fetal limbs anatomy and fetal limbs malformations using a systematic continuous sequence approach].

OBJECTIVE: To review the value of ultrasonographic evaluation on fetal limbs anatomy and malformations in prenatal diagnosis using a systematic continuous sequence approach (SCSA). METHODS: Successive 4,932 prenatal ultrasonographic evaluation during gestation aging 14 - 40 weeks from August 2000 to September 2002 entered the present review. SCSA was applied to scan each limb of the fetus respectively. RESULTS: The anatomic structures of the four limbs of the fetus were clearly displayed and correctly recognized on ultrasonic images using the SCSA in 4 750 cases (96.3%). Ninety eight limb malformations of 34 fetuses were correctly diagnosed (87.2%). Whereas 16 malformations of 5 fetuses were missed to recognize (12.8%). The diagnoses were confirmed after subsequent labor or induced labor. The sensitivity, specificity, accuracy, positive and negative predictive values were 87.2%, 99.8%, 99.2%, 81.0% and 99.9%, respectively. CONCLUSION: The majority of fetal limb structures and malformations can be clearly demonstrated on prenatal ultrasonic imaging using SCSA. SCSA for prenatal ultrasonographic evaluation of the fetal limbs is a reliable and accurate diagnostic modality so far as the skills become more sophisticated.

[Research on genetic variation of heart fatty acid-binding protein gene in ten pig breeds].

The genetic variation of heart fatty acid-binding protein (H-FABP) gene in 561 pigs including Duroc, Landrace, Large Yorkshire, Nanchang white pig, Erhualian, Meishan, Yushan black pig, Leping spotted pig, Jinhua black head-hind pig and Shanggao black head-hind pig were detected by PCR-RFLP with Hinf I, Hae III and Msp I. The results showed as follows: (1) Nanchang white pig presented only HH genotype while other breeds varied at the Hinf I-RFLP site; (2) The exotic breeds including Duroc, Landrace, Large Yorkshire and the native breed Nanchang white pig were proved to be polymorphic while the five Chinese local breeds presented no variation at the Hae III-RFLP site; (3) Among the tested breeds only Duroc presented variation at the Msp I-RFLP site. It is noted that all the Chinese local breeds present as AADD--genotypes.