Objective To determine the clinical indications and detection efficiency of non-invasive prenatal testing (NIPT) in Jiangsu Province, China. Methods A total of 13 041 pregnant women from nine hospitals in Jiangsu Province who voluntarily accepted NIPT for chromosome 13, 18, 21 and sex chromosome from January 1, 2012 to December 31, 2013 were analyzed retrospectively. All cases were singleton pregnancies and spontaneously conceived. Invasive prenatal diagnosis followed by fetal chromosome karyotype analysis was recommended in high-risk women following NIPT. The clinical indications and positive predictive value of NIPT were conducted. Results NIPT detected 88, 19, 9 and 64 cases at high risk for trisomy 21, trisomy 18, trisomy 13 and X chromosome aneuploidy, and the positive rate was 0.67%, 0.15%, 0.07% and 0.49%, respectively. Among the 74, 13, 8 and 44 high-risk cases who accepted chromosome karyotype analysis, respectively, 67 cases were diagnosed with trisomy 21, 12 cases with trisomy 18, one case with trisomy 13, and 18 cases with numerical X chromosome abnormality. The positive predictive value was 90.5% (67/74), 12/13, 1/8 and 40.9% (18/44), respectively. One pregnant woman who was reported as high-risk trisomy 21 following NIPT, but high-risk trisomy 18 at prior serum screening, was eventually diagnosed with fetal trisomy 18 by chromosome karyotype analysis, whose placenta was a mosaic of trisomy 21 and trisomy 18. High-risk following serum screening was the most common indication for NIPT accounting for 46.4% (6 056/13 041), followed by low-risk but asking for testing (28.9%, 3 773/13 041) and advanced age (20.5%, 2 673/13 041). Conclusions High-risk, low-risk but asking for testing and advanced maternal age are common indications for NIPT in Jiangsu Province. The positive predictive value of NIPT for trisomy 21 or trisomy 18 is relatively high, but is much lower for trisomy 13 or X chromosome aneuploidy.

Objective To observe the effects of intensive lower extremity motor control training on the motor function of lower extremity, balance and walking capability of stroke patients. Methods 40 stroke patients were randomized into the intervention group (n=20) and control group (n=20). Both groups received the routine rehabilitation, while the intervention group accepted the lower extremity motor control training in addition for 6 weeks. Before and after 6 weeks of treatments, they were assessed with Fugl-Meyer Assessment of lower extremity (FMA-L), Berg Balance Scale (BBS), Holden Functional Ambulation Category (FAC); their gaits were analysesd with footprint. Results Both groups improved significantly in scores of FMA-L, BBS, FAC and average step length, stride width, walking velocity (P<0.01) after treatment, and improved more in the intervention group than in the control group (P<0.05). Conclusion Intensive motor control training of lower extremity may promote the recovery of motor function of lower extremities, balance and walking ability of stroke patients.

Objective To discuss the detection rate of chromosomal abnormalities in women with different indications for invasive prenatal diagnosis(amniocentesis and eordocentesis), and the procedure-related complications. Metheds A retrospective analysis was conducted on 1264 women, who underwent invasive prenatal diagnosis (1082 amniocentesis and 182 eordocentesis), and the procedure-related complications were reviewed. Results The indications for invasive prenatal diagnosis in these 1264 women were: increased risk at prenatal screening (651, 51.5%), advanced maternal age (≥35) (318, 25.2%), abnormal foundings through uhrasonograph (136, 10.8%),history of adverse pregnancy (88, 6.9%), one or two abnormal serologic markers (52,4.1%), and chromosomal balance translocation carrier in either one of the couple(19, 1.5%). Thirty-seven cases were found to be chromosomal abnormalities with clinic significance and the indications for them were: ultrasonic abnormality (20/136, 14.7%); increased risk at prenatal screening (12/651, 1.8%); one or two abnormal serologic markers (1/52, 1.9%); history of adverse-pregnant (1/88, 1.1%)chromosomal balance translocation carrier in either one of the couple (3/19, 15.8%); advanced maternal age (0/318). Among the 1264 cases, 5 experienced spontaneous abortion and the procedure-related fetal loss rates were 0.28% for amniocentesis (3/1082) and 1.09% for cordocentesis (2/182), P=0. 154. The rate of complications after cordocentesis was significantly higher than amniocentesis (9.89 % vs 0.18 %, P= 0.0001). Conclusions Routine fetal karyotyping should be prompted after prenatal ultrasonographic abnormalities. However, invasive prenatal diagnosis due to advanced maternal age alone is controversial. Amniocentesis is the fist choice for invasive prenatal diagnosis.

Objective To evaluate the outcome of ST-segment elevation myocardial infarction (STEMI) patients received different reperfusion therapies. Methods The 238 consecutive STEMI patients were enrolled from February 2012 to December 2012. According to the current guideline of PCI and the choice of patients, the patients were divided into the groups of percutaneous coronary intervention (PCI), ifbrinolysis, and conservative medication. The major adverse cardiac events (MACE) was analyzed in a follow up of 6 months. Results (1) The enrolled patients included the 210 patients received PCI (88.2%), 14 patients received fibrinolysis (5.9%) and 14 patients received conservative medication (5.9%).The Median time of D2B was 110minutes.(2) The rate of late stent thrombosis was signiifcant higher in BMS than DES (n=2, 2.8%vs 0, P < 0.05) . (3) The PCI group had a signiifcantly higher incidence of stroke than the ifbrinolysis group and the conservative medication group (1.0%vs 0, P < 0.05;1.0%vs 0, P<0.05). (4) The PCI group had a signiifcantly higher incidence of bleeding compared to the thrombolysis group and the medication group (1.0% vs 0, P < 0.05; 1.0% vs 0%, P < 0.05). Conclusions The majority of STEMI patients received PCI;The D2B time, which was required<90 minutes in guideline of PCI, was found delayed in our study;Compared to ifbrinolysis and conservative medication, PCI showed better clinical outcomes of STEMI patients.

RhD-negative pregnant women with an RhD-positive fetus are at risk of hemolytic disease of the fetus and newborn (HDFN), which may lead to fetal/neonatal death. While these would not affect those RhD-negative fetuses. With the advancement of technology in genetics, the administration of anti-D immunoglobulin to women with an RhD-positive fetus could reduce the risk of HDFN. Therefore, non-invasive prenatal testing on fetal RHD genotype plays an important role in the management of RhD-negative pregnant women. Selective usage of anti-D immunoglobulin is important in perinatal management in these women. The non-invasive prenatal screening for fetal RHD gene which has been carried out in Caucasian is not applicable to Asians because of the difference in RHD genotype. In addition to complete or partial RHD gene deletion, point mutations are also common RHD genotypes among Asians. This enlightens us to establish a non-invasive prenatal screening method for Asians. This article reviews the progress of fetal RHD screening in Asian RhD-negative pregnant women.

OBJECTIVE: To analyze the cause and pregnancy outcome for non-reportable cell-free DNA (cfDNA) results during non-invasive prenatal testing (NIPT). METHODS: cfDNA was extracted from maternal plasma from 5898 singleton pregnancies at 12 to 22 gestational weeks and underwent NIPT with strict quality control standards. For those with sub-standard results, redraw or invasive prenatal procedures were recommended. RESULTS: Among the 5898 cases, 32 have failed for the initial NIPT, including 17 cases with substandard cffDNA%, 10 cases with data fluctuation after twice library constructing and sequencing, and 5 cases with unidentifiable sex chromosome abnormalities. For these 32 cases, 2 directly underwent amniocentesis, and karyotyping analysis showed both were normal. Six of the 30 redrawn cases finally turned out to be nonreportable. The final nonreportable rate was therefore 0.1% (8/5898). Of the redrawn cases, 1 trisomy 21, 1 trisomy 18 and 1 trisomy 13 high risk-cases were identified, which were all confirmed to be false positive. Among the 6 nonreportable cases, 2 women underwent invasive prenatal testing, and 1 was found to have a normal fetal karyotype, while another was found to have an abnormal karyotype of mos45,X[32]/46,XY[18]. The other 4 nonreportable cases who did not accept invasive prenatal testing have all reported normal child development at follow-up. CONCLUSION The main reason for nonreportable NIPT results was low cffDNA%. The high success rate of the redrawn cases has effectively increased the overall NIPT success rate and reduced the number of the cases necessitating invasive prenatal diagnosis. The initially nonreportable women may consider retesting after careful counseling with informed consent.
Aneuploidy ; Child ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Noninvasive Prenatal Testing ; Pregnancy ; Prenatal Diagnosis ; Trisomy ; Trisomy 18 Syndrome/genetics*

Objective:To evaluate the value of 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT/CT imaging for the identification of dystonic muscles in patients with primary cervical dystonia (PCD). Methods:A total of 10 patients with PCD (3 males, 7 females, age (47.3±9.9) years) and 10 healthy subjects (4 males, 6 females, age (43.5±9.4) years; control group) between August 2019 and October 2021 in China-Japan Friendship Hospital were enrolled prospectively. All subjects underwent 99Tc m-MIBI SPECT/CT scan. The SUV max of 8 bilateral representative muscles, including rectus capitis posterior major, obliquus capitis inferior, splenius capitis, semispinalis, sternocleidomastoid, trapezius, musculus scalenus muscle and levator scapulae were evaluated in control group. In PCD group, muscles with abnormal uptake were determined. ROI was drawn and SUV max was measured. Independent-sample t test was used to analyze the differences of SUV max between normal and abnormal muscles. The detecting rates of neck MRI and SPECT/CT for abnormal muscles were analyzed by χ2 test. Results:Normal muscles of healthy subjects showed mild symmetrical radioactivity distribution, with the SUV max of 1.10±0.19. A total of 60 muscles with abnormal uptake in 10 patients were found, including 7 rectus capitis posterior major, 10 obliquus capitis inferior, 8 splenius capitis, 8 semispinalis, 10 sternocleidomastoid, 5 trapezius, 3 musculus scalenus muscle and 9 levator scapulae. The SUV max of muscles with abnormal uptake was 1.81±0.43, which was higher than that of normal muscles ( t=17.05, P<0.001). Only 30 pieces abnormal hypertrophy muscle were found by neck MRI, and the detecting rate was much lower than that of SPECT/CT (18.75%(30/160) vs 37.50%(60/160); χ2=28.03, P<0.001). Conclusion:99Tc m-MIBI SPECT/CT may be a useful method for identifying dystonic muscles and a guide to precision therapy in patients with PCD.

OBJECTIVETo use different technologies to distinguish true and pseudo mosaicisms among cultured amniocytes in order to attain more accurate diagnosis.

METHODSWith informed consent, 20 mL of amniotic fluid was obtained from pregnant women at between 18 to 24 gestational week. Each amniotic fluid sample was processed as two separate lines for the culturing, observation, harvesting and analysis. All procedures were conducted conforming to the Technology Standards of Cytogenetic Prenatal Diagnosis of Fetal Chromosome Abnormalities issued by the Ministry of Health in 2010. Umbilical cord blood, fluorescence in situ hybridization (FISH), single nucleotide polymorphism array (SNP-array) and flow cytometer were applied when necessary.

RESULTSAmong 3910 cases, 128(3.3%) were detected as mosaicisms. Further analysis with the above technologies has verified 6 cases as true mosaicisms and the remaining 120 as pseudomosaicisms. For one case detected by karyotype analysis as 47, XXY/46, XY, the ratio of different cell lines was confirmed by FISH as 1:2. Another case, detected by karyotype analysis as 47, XX,+mar/46, XX (1:1), was verified by SNP-array as 18p duplication. A suspected polyploidy mosaicism was rejected by flow cytometry and cord blood karyotyping.

CONCLUSIONTwo separate cell cultures are important for distinguishing true and pseudo mosaicisms. Combined FISH, SNP-array and flow cytometry can attain more reliable and accurate diagnosis for mosaicisms.

Adult ; Amniotic Fluid ; cytology ; metabolism ; Cells, Cultured ; Chromosome Disorders ; diagnosis ; embryology ; genetics ; Chromosomes, Human, Pair 18 ; genetics ; Cytogenetic Analysis ; methods ; Female ; Fetal Diseases ; diagnosis ; genetics ; Genetic Testing ; methods ; Gestational Age ; Humans ; In Situ Hybridization, Fluorescence ; Karyotype ; Karyotyping ; Microarray Analysis ; methods ; Mosaicism ; Polymorphism, Single Nucleotide ; Pregnancy ; Prenatal Diagnosis ; methods ; Trisomy ; diagnosis ; genetics ; Trisomy 18 Syndrome

OBJECTIVETo provide genetic analysis for a family affected with Duchenne muscular dystrophy (DMD) with a recurrent de novo mutation.

METHODSMultiplex ligation dependent probe amplification (MLPA) was used to detect potential deletion and duplication of the DMD gene, and the DNA products were sequenced on a Genetic Analyzer 3130 sequencer. Haplotype analysis was performed using four short tandem repeat polymorphism loci (44C/A, 45C/A, 49C/A and 63C/A) of the DMD gene for the family.

RESULTSA same deletional mutation (Del 48-50) of the DMD gene was detected in the proband and fetus, but not in their mother. The proband and fetus have inherited the same haplotype of the DMD gene from their mother. The fetus was predicted to be affected by the disease.

CONCLUSIONAbove findings suggested that the mother was very likely to have a germline mosaicism for the DMD gene mutation. For the de novo DMD mutation, although genetic analysis of peripheral blood DNA has indicated that the proband's mother was not a carrier, germline mosaicism could still not be ruled out, and prenatal gene diagnosis should be provided for subsequent pregnancies.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; China ; Dystrophin ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Infant ; Male ; Molecular Sequence Data ; Mosaicism ; Muscular Dystrophy, Duchenne ; embryology ; genetics ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Sequence Deletion

OBJECTIVE: To assess the application value of noninvasive prenatal testing (NIPT) based on cell-free fetal DNA. METHODS: The results of 2777 cases of basic and extended NIPT were retrospectively analyzed. The clinical data and outcome of pregnancy were analyzed, in addition with the diagnosis rate and testing efficiency. RESULTS: Among the 2777 pregnant women, 1192 (42.9%) had accepted basic NIPT and 1585 (57.1%) accepted extended NIPT. With a failure rate of 0.1%, 8 and 6 cases were reported respectively as high-risk pregnancies for trisomy 21 and sex chromosomal abnormalities. Other genetic abnormalities were detected in 32 cases. The positive predictive value for trisomy 21 was 85.7%, and one case of 47,XXX was diagnosed among 3 women with high risks for sex chromosomal abnormalities. For those with a high risk for other genetic abnormalities, pregnant diagnosis rates of basic and extended NIPT were 71.4% (5/7) and 68.2% (15/22), respectively. Seven copy number variations (CNVs) were confirmed, including one pathogenic CNV, one likely pathogenic CNV and 5 variants of unknown significance. Among 6 cases with high-risk of maternal CNVs, 5 fetuses and the mothers were confirmed to be carriers. No CNV was detected in the remainder fetus by chromosomal microarray analysis, while its mother was a carrier of the corresponding CNV. CONCLUSION NIPT has shown a relatively high positive predictive value for the screening of trisomy 21 and maternal CNVs but with a limited efficiency for the discovery of fetal CNVs. For other genetic abnormalities signaled by NIPT, informed choice by the pregnant women during pre-testing consultation is recommended. Invasive prenatal diagnosis should be considered in the combination of NIPT reports and fetal ultrasound, while the residual risks should be fully informed.
Aneuploidy ; Cell-Free Nucleic Acids/genetics* ; DNA/genetics* ; DNA Copy Number Variations ; Female ; Fetus ; Humans ; Noninvasive Prenatal Testing ; Pregnancy ; Retrospective Studies