Feasibility and safety of fetal intravascular transfusion via the intrahepatic vein in the treatment of fetal anemia / 中华妇产科杂志

Objective:To investigate the feasibility and safety of fetal intravascular transfusion via the intrahepatic vein in the treatment of fetal anemia.Methods:This was a retrospective analysis of all fetuses requiring intrauterine transfusion (IUT) in the Shanghai First Maternity and Infant Hospital between January 2010 and December 2019. According to the different ways of IUT, they were divided into intrahepatic venous transfusion group and umbilical venous transfusion group, fetal outcomes and the incidence of procedure-related complications between the two groups were compared.Results:A total of 97 IUTs were performed on 48 fetuses. Among them, 16 cases were performed in the intrahepatic vein (31 transfusions), 32 cases were performed in the cord of the umbilical vein (66 transfusions).There were no significant differences between the two groups in age, labor history and the proportion of fetal hydrops before the first transfusion. In the intrahepatic venous transfusion group, the posterior placenta was 14/16, which was significantly higher than 78% (25/32) in the umbilical venous transfusion group ( P<0.01). The live-birth rates of the two groups were 13/16 and 75% (24/32). There was no significant difference between the two groups ( P>0.05). Before intrahepatic venous transfusion, the proportion of fetal hydrops was significantly higher than that of umbilical venous transfusion [55% (17/31) vs 24% (16/66), P<0.05]. Puncture success rate of intrahepatic venous transfusion and umbilical venous transfusion were both 100%. In the umbilical venous transfasion group, the incidence of needle slippage (5%, 3/66) and the abnormality of fetal heart rate (11%, 7/66) were higher than those in the intrahepatic venous transfasion group [0 and 3% (1/31)], but there were no significant differences between the two groups (all P>0.05). There were no cases of fetal loss within 24 hours, premature rupture of membranes, infection within 7 days and emergency cesarean section after IUT in both groups. Conclusions:Fetal intravascular transfusion via the intrahepatic vein is safe and feasible in the treatment of fetal anemia. But the requirements of puncture technique are relatively high, so it is recommended to be carried out in experienced fetal treatment center.

Human acellular amniotic membrane scaffold promotes ligament differentiation of human amniotic mesenchymal stem cells modified by scleraxis in vitro / 中国组织工程研究

BACKGROUND: Acellular amniotic membrane is a natural biomaterial scaffold, which has been widely used in related fields of tissue engineering. Scleraxis gene plays an important regulatory role in the formation of connective tissues such as ligaments. OBJECTIVE: To verify the biocompatibility of Scleraxis modified human amniotic mesenchymal stem cells and human acellular amniotic membrane scaffold complex in rats. METHODS: The amniotic membrane tissues of the placenta at term were taken, and the fresh human amniotic membrane was decellularized by chemical-enzymatic digestion method. Two-step enzyme digestion method was used to separate human amniotic mesenchymal stem cells from human fresh amniotic membrane. The third-generation human amniotic mesenchymal stem cells were transfected with Scleraxis lentivirus, which were then cultured with human decellularized amniotic membrane for 5, 10, and 15 days so as to detect mRNA expression of related genes. The 18 Sprague-Dawley rats were randomly divided into three groups. In the experimental group, the prepared cell scaffold complex was implanted into the subcutaneous fascia of the back of the rat. In the negative control group, an incision was made on the back of the rat, without implanting materials. In the blank control group, no treatment was performed. Hematoxylin-eosin staining was performed on the operation area tissues 1 and 4 weeks after surgery. Immunohistochemical staining of CK protein was performed on the operation area tissues 4 weeks after surgery. RESULTS AND CONCLUSION: (1) Scleraxis gene transfection of human amniotic mesenchymal stem cells and human acellular amniotic membrane compound culture could significantly up-regulate the mRNA expression levels of ligament differentiation-related genes type I collagen, type III collagen, fibronectin and cytocontin C. (2) The neonatal granulation tissue was seen in the local tissue of the experimental group at 1 week after surgery, and the inflammatory response was heavier than that of the negative control group and the blank control group. At 4 weeks after surgery, the local tissue arrangement of the experimental group tended to be neat; the granulation tissue was reduced; and the inflammation subsided obviously. (3) The CK protein expression was positive in the experimental group at 4 weeks after the operation; the local tissues were neatly arranged; and a large number of cells were attached around the amniotic membrane tissue. (4) Results suggested that co-culture of Scleraxis gene transfected human amniotic mesenchymal stem cells with human acellular amniotic membrane scaffold can promote the differentiation of human amniotic mesenchymal stem cells into ligaments in vitro, and the cell scaffold complex shows good biocompatibility in animals.

Scleraxis lentivirus-transfected human amniotic mesenchymal stem cells promote tendon-bone healing in Rabbits / 中国组织工程研究

BACKGROUND: Human amniotic mesenchymal stem cells have a wide variety of sources, low immunogenicity, and multilineage differentiation potential. Studies have confirmed that Scleraxis gene can induce human amniotic mesenchymal stem cells to differentiate into ligaments and accelerate tendon-bone healing. OBJECTIVE: To explore whether Scleraxis induces human amniotic mesenchymal stem cells to promote tendon-bone healing in vivo in rabbits, providing new options for clinical treatment of tendon-bone healing. METHODS: The study protocol was approved by the Ethic Committee of the Affiliated Hospital of Zunyi Medical University, and written informed consent was obtained from each puerpera. The healthy full-term maternal placenta was taken and cultured, and human amniotic mesenchymal stem cells were isolated and cultured by trypsin digestion twice. Then the morphology of the cells was observed under an inverted microscope, and the cells were further cultured until the third generation for subsequent experiments. The lentivirus carrying the Scleraxis gene was transfected into human amniotic mesenchymal stem cells in vitro. Expression levels of ligament-related genes were detected by real-time fluorescent quantitative PCR, and the expression levels of related proteins were detected by immunofluorescence. Human amniotic mesenchymal stem cells transfected with Scleraxis gene were injected into the extraarticular tendon-bone model of rats. After 3 months, specimens were taken to observe the tendon-bone healing. RESULTS AND CONCLUSION: (1) Human amniotic mesenchymal stem cells from passage to third generation showed long fusiform and vortex-like adherent growth under the inverted phase contrast microscope. (2) The third-generation human amniotic mesenchymal stem cells expressed green fluorescence after 24 hours of infection with the Scleraxis gene lentivirus, and the fluorescence expression was strong and stable. (3) Cell counting kit-8 findings indicated that lentivirus transfection of Scleraxis gene showed no influence on the cell growth rate. (4) Real-time fluorescent quantitative PCR findings showed that the mRNA expression of Scleraxis and ligament-related genes type I collagen, type III collagen, Fibronectin and Tenascin-C was significantly increased after lentivirus transfection of Scleraxis gene. (5) The results of immunofluorescence showed that the expression levels of ligament-related proteins type I collagen, type III collagen, Fibronectin and Tenascin-C were increased after lentivirus transfection of Scleraxis gene. To conclude, in vivo animal experiments have confirmed that the lentivirus transfection of Scleraxis gene can accelerate the tendon-bone healing of the rabbit extraarticular tendon-bone model.

In vitro construction of human amniotic mesenchymal stem cell sheet and its osteogenic differentiation / 中国组织工程研究

BACKGROUND: Human amniotic mesenchymal stem cells (hAMSCs) are a kind of adult stem cells that can be extracted from discarded placenta. Compared with other mesenchymal stem cells, hAMSCs have many advantages such as noninvasive isolation, low immunogenicity and short growth cycle, and thus hAMSCs are an important source of tissue engineering seed cells. Currently, hAMSCs have been applied in the clinical treatment of diabetes. OBJECTIVE: To explore a simple method to fabricate hAMSC sheets and to study their potential to differentiate into osteocytes. METHODS: Passage 3 hAMSCs were seeded into culture plates at a high density, and the sheet-forming medium was added to fabricate hAMSC sheet. The structural characteristics of hAMSC sheets were evaluated by histological staining and scanning electron microscopy. The sheet-forming induction medium was added to the passage 3 hAMSCs for 7 continuous days, and then replaced by the osteogenic induction medium for 14 days to construct osteogenic-induced hAMSC sheets. The potential for osteogenic differentiation of hAMSC sheets was assessed by alizarin red staining, immunohistochemical staining, alkaline phosphatase activity, RT-PCR, and western blot assay. RESULTS AND CONCLUSION: Hematoxylin-eosin staining results indicated that hAMSC sheets had a multi-layered structure with the cells stacked layer-by-layer and evenly distributed. Under the scanning electron microscope, the hAMSC sheets had a multi-layered structure, and a large amount of extracellular matrices that enveloped the fusiform cells were produced. After 14 days of osteogenic induction, orange-red precipitation was observed by alizarin red staining. Immunohistochemical staining results showed a large amount of type II collagen. Compared with non-induced hAMSC sheet, alkaline phosphatase activity was significantly increased in the osteogenic induced sheet (P < 0.01). The expression levels of type I collagen, osteocalcin, and Runt-related transcript factor 2 mRNA and protein were significantly higher in the osteogenic-induced hAMSC sheet group than the non-induced hAMSC sheet group (P < 0.05). Our findings indicate that this is a simple and economic method to construct the hAMSC sheets in the normal culture medium. Moreover, hAMSC sheets have a good osteogenic differentiation potential that has been confirmed in vitro.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Cardiac electrical and mechanical synchrony of super-responders to cardiac resynchronization therapy / 中华医学杂志(英文版)

BACKGROUND@#Super-responders (SRs) to cardiac resynchronization therapy (CRT) regain near-normal or normal cardiac function. The extent of cardiac synchrony of SRs and whether continuous biventricular (BIV) pacing is needed remain unknown. The aim of this study was to evaluate the cardiac electrical and mechanical synchrony of SRs.@*METHODS@#We retrospectively analyzed CRT recipients between 2008 and 2016 in 2 centers to identify SRs, whose left ventricular (LV) ejection fraction was increased to ≥50% at follow-up. Cardiac synchrony was evaluated in intrinsic and BIV-paced rhythms. Electrical synchrony was estimated by QRS duration and LV mechanical synchrony by single-photon emission computed tomography myocardial perfusion imaging.@*RESULTS@#Seventeen SRs were included with LV ejection fraction increased from 33.0 ± 4.6% to 59.3 ± 6.3%. The intrinsic QRS duration after super-response was 148.8 ± 30.0 ms, significantly shorter than baseline (174.8 ± 11.9 ms, P = 0.004, t = -3.379) but longer than BIV-paced level (135.5 ± 16.7 ms, P = 0.042, t = 2.211). Intrinsic LV mechanical synchrony significantly improved after super-response (phase standard deviation [PSD], 51.1 ± 16.5° vs. 19.8 ± 8.1°, P < 0.001, t = 5.726; phase histogram bandwidth (PHB), 171.7 ± 64.2° vs. 60.5 ± 22.9°, P < 0.001, t = 5.376) but was inferior to BIV-paced synchrony (PSD, 19.8 ± 8.1° vs. 15.2 ± 6.4°, P = 0.005, t = 3.414; PHB, 60.5 ± 22.9° vs. 46.0 ± 16.3°, P = 0.009, t = 3.136).@*CONCLUSIONS@#SRs had significant improvements in cardiac electrical and LV mechanical synchrony. Since intrinsic synchrony of SRs was still inferior to BIV-paced rhythm, continued BIV pacing is needed to maintain longstanding and synchronized contraction.

Safety and efficacy of radiofrequency ablation for twin reversed arterial perfusion sequence / 中华围产医学杂志

Objective:To assess the safety and efficacy of radiofrequency ablation (RFA) in the treatment of twin reversed arterial perfusion (TRAP) sequence.Methods:This was a retrospective study of all TRAP sequence cases treated by RFA in Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, between January 1, 2012, and December 31, 2018. Perioperative complications, short- and long-term perinatal outcomes, and maternal complications were analyzed by analysis of variance, Kruskal-Wallis test, Chi-square test, or Fisher's exact test. Results:(1) This study recruited 59 pregnant women with an average age of (28.4±4.0) years. The mean gestational age at TRAP sequence diagnosis was (17.0±4.1) weeks, and 23 (39.0%) were diagnosed before 16 weeks. (2) The 59 cases consisted of 45 (76.2%) monochorionic diamniotic (MCDC) twins, five (8.5%) monochorionic monoamniotic (MCMA) twins, four (6.8%) monochorionic triamniotic (MCTA) triplets and five (8.5%) dichorionic triamniotic (DCTA) triplets. Fifty-four cases (91.5%) were acardius acephalus, four (6.8%) were acardius anceps, and one (1.7%) was acardius amorphous. (3) Preterm premature rupture of membranes (PPROM) was a leading complication following RFA with an overall incidence of 25.4% (15/59). PPROM before 28 and at 28-34 gestational weeks occurred in seven (11.9%) and five (8.5%) cases, respectively, leading to fetal loss in six cases. The cumulative incidence of PPROM within one week, two weeks, and one month after RFA was 5.1% (3/59), 6.8% (4/59) and 10.2% (6/59), respectively. No chorioamnionitis, blood transfusion due to hemorrhage, placental abruption, sepsis, bowel perforation, or other maternal complications were reported during or after the procedure. (4) No abnormalities of the nervous system were found in any fetus on postoperative MRI during pregnancy. The mean interval from treatment to delivery was (14.9±7.1) weeks. Twelve pump twins (20.3%) were lost after RFA, while the other 47 (79.7%) were delivered and survived until 28 days after birth, including 18 premature infants and 29 full-term infants. Eight premature infants were admitted to the neonatal intensive care unit (NICU). Intraventricular hemorrhage, neonatal respiratory distress syndrome (NRDS), and NRDS complicated by necrotizing enterocolitis occurred in three different babies who recovered after appropriate treatment. (5) Of the 59 patients, 56 (94.9%) received intrauterine interventions after 16 gestational weeks, and the survival rate of the pump twins was 78.6% (44/56). Three patients (5.1%) received intrauterine interventions before 16 weeks of gestation with all pump twins survived. (6) Of the 45 MCDA twins, 37 (82.2%) survived and were born at a mean gestational age of 38.0 (26.5-41.0) weeks. Three out of the five MCMA twins survived with the median gestational age at birth of 33.5 (32.0-37.0) weeks. Of the nine triplets, seven survived and delivered at the median gestational age of 37.1 (29.2-40.0) weeks. (7) The needle pierced through the placenta during RFA in 23 (39.0%) cases, but not in the rest 36 (61.0%) cases. After excluding four cases opting for pregnancy termination, statistical analysis showed no significant difference in the incidence of PPROM or intrauterine death, or the 28-day survival rate of the pump twins when comparing those cases with the needle going or not going through the placenta. (8) At the final follow-up (December 2019), 47 surviving pump infants were growing normally without any severe neurological sequelae.Conclusions:RFA appears to be a relatively safe and reliable technique in the treatment of TRAP sequence to improve the perinatal outcomes of pump twins.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Microvolt T-wave alternans complemented with electrophysiologic study for prediction of ventricular tachyarrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy: a long-term follow-up study / 中华医学杂志(英文版)

Background@#The long-term predicted value of microvolt T-wave alternans (MTWA) for ventricular tachyarrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains unclear. Our study explored the characteristics of MTWA and its prognostic value when combined with an electrophysiologic study (EPS) in patients with ARVC.@*Methods@#All patients underwent non-invasive MTWA examination with modified moving average (MMA) analysis and an EPS. A positive event was defined as the first occurrence of sudden cardiac death, documented sustained ventricular tachycardia (VT), ventricular fibrillation, or the administration of appropriate implantable cardioverter defibrillator therapy including shock or antitachycardia pacing.@*Results@#Thirty-five patients with ARVC (age 38.6 ± 11.0 years; 28 males) with preserved left ventricular (LV) function were recruited. The maximal TWA value (MaxValt) was 17.0 (11.0–27.0) μV. Sustained VT was induced in 22 patients by the EPS. During a median follow-up of 99.9 ± 7.7 months, 15 patients had positive clinical events. When inducible VT was combined with the MaxValt, the area under the curve improved from 0.739 to 0.797. The receiver operating characteristic curve showed that a MaxValt of 23.5 μV was the optimal cutoff value to identify positive events. The multivariate Cox regression model for survival showed that MTWA (MaxValt, hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.01–1.11; P = 0.01) and inducible VT (HR, 5.98; 95% CI, 1.33–26.8; P = 0.01) independently predicted positive events in patients with ARVC.@*Conclusions@#MTWA assessment with MMA analysis complemented by an EPS might provide improved prognostic ability in patients with ARVC with preserved LV function during long-term follow-up.

Microvolt T-wave alternans complemented with electrophysiologic study for prediction of ventricular tachyarrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy: a long-term follow-up study / 中华医学杂志(英文版)

BACKGROUND@#The long-term predicted value of microvolt T-wave alternans (MTWA) for ventricular tachyarrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains unclear. Our study explored the characteristics of MTWA and its prognostic value when combined with an electrophysiologic study (EPS) in patients with ARVC.@*METHODS@#All patients underwent non-invasive MTWA examination with modified moving average (MMA) analysis and an EPS. A positive event was defined as the first occurrence of sudden cardiac death, documented sustained ventricular tachycardia (VT), ventricular fibrillation, or the administration of appropriate implantable cardioverter defibrillator therapy including shock or anti-tachycardia pacing.@*RESULTS@#Thirty-five patients with ARVC (age 38.6 ± 11.0 years; 28 males) with preserved left ventricular (LV) function were recruited. The maximal TWA value (MaxValt) was 17.0 (11.0-27.0) μV. Sustained VT was induced in 22 patients by the EPS. During a median follow-up of 99.9 ± 7.7 months, 15 patients had positive clinical events. When inducible VT was combined with the MaxValt, the area under the curve improved from 0.739 to 0.797. The receiver operating characteristic curve showed that a MaxValt of 23.5 μV was the optimal cutoff value to identify positive events. The multivariate Cox regression model for survival showed that MTWA (MaxValt, hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.01-1.11; P = 0.01) and inducible VT (HR, 5.98; 95% CI, 1.33-26.8; P = 0.01) independently predicted positive events in patients with ARVC.@*CONCLUSIONS@#MTWA assessment with MMA analysis complemented by an EPS might provide improved prognostic ability in patients with ARVC with preserved LV function during long-term follow-up.

Prenatal diagnosis for a pedigree affected with Wolf-Hirschhorn syndrome due to a subtle chromosomal translocation / 中华医学遗传学杂志

OBJECTIVE@#To make molecular diagnosis of an infant affected with severe developmental delay and multiple birth defects, assisting prenatal diagnosis for the second pregnancy.@*METHODS@#Standard G-banded karyotyping was performed for the fetus and his parents. Single nucleotide polymorphism array (SNP array) was used to detect submicroscopic chromosomal aberration. Fluorescence in situ hybridization (FISH) was employed to determine the parental origin of the aberration.@*RESULTS@#Both the proband and the fetus harbored a 5.4 Mb distal 4p deletion and a 6.9 Mb distal 6q duplication. FISH confirmed that the mother has carried a balanced translocation involving 4p and 6q.@*CONCLUSION@#The unbalanced chromosomal aberration in the proband and the fetus were both derived from the mother. Both patients showed a Wolf-Hirschhorn syndrom phenotype and partial phenotype of 6q trisomy. SNP array combined with FISH are essential for the detection of cryptic chromosomal aberrations which may be missed by coventional karyotyping analysis.

Sex chromosome aneuploidy screened by non-invasive prenatal testing from 35827 singletons: prenatal diagnosis and pregnancy determinations / 中华围产医学杂志

Objective To assess the positive predictive value (PPV) of fetal sex chromosome aneuploidy (SCA) identified by non-invasive prenatal testing (NIPT) and investigate families' acceptance of SCA fetus. Methods All suspected SCA cases screened by NIPT from singletons were reviewed in Prenatal Diagnosis Center of Shanghai First Maternity and Infant Hospital from April 1, 2015 to October 31, 2017. Maternal age, NIPT indications, prenatal diagnosis protocols, testing results and their pregnancy determinations were analyzed. Results NIPT was provided to 35827 singletons and 86 suspected SCA cases were identified out of 35823 successful ones, giving a positive detection rate of 0.24％. The average maternal age was (31.5±5.0) years. After genetic counseling, 20 patients declined prenatal diagnosis,the rest 66 cases proceeded with aminiocentesis and fetal chromosomal testing, of which 32 were cytogenetically diagnosed as SCA with the PPV of 48.5％ . The SCA fetus consisted of 25 sex chromosome trisomies (seven cases of 47,XXX, three cases of 47,XYY and 15 cases of 47,XXY), one monosomy X (45,X), three mosacisms (47,XXY/48,XXYY, 47,XXX/45,X, 45,X/46,XX, one for each) and three microdeletions/microduplications. Besides, two false positive NIPT cases were proved to be low level of maternal mosacism (45,X/46,XX, 5％ and 10％ for each). After genetic counseling, 17 out of 20 who declined prenatal diagnosis and 9 out of 32 who diagnosed fetal SCAs continued their pregnancies, with a combined proportion of continued pregnancy of 50％. Thirty-four pregnancies were also continued after exclusion of SCA. Interestingly, the proportion of continued pregnancy among those sex chromosomal trisomy fetuses was only 32％(8/25). Conclusions As a safe and rapid prenatal testing for common autosomal aneuploidies, NIPT could also identify some types of SCA, but with relatively low PPV. More long-term researches are required to determine its sensitivity and specificity. For some types of SCA with mild phenotypes, some family would continue the pregnancy. Therefore, limitations of NIPT should be appropriately explained during both pre- and post-testing counseling.

Clinical outcomes of non-immune hydrops fetalis in the era of intrauterine intervention: a single centered retrospective analysis / 中华围产医学杂志

Objective To investigate the pregnancy outcomes of non-immune hydrops fetalis (NIHF) in the era of intrauterine intervention. Methods We reviewed the medical records of 149 patients who were referred for NIHF and delivered at Fetal Medicine Unit, Shanghai First Maternity and Infant Hospital between March 2012 and March 2017. After systematic evaluation and consultation, 102 cases chose to terminate their pregnancies, 47 cases (31.5％) chose to continue their pregnancies, among which two cases were lost to follow-up. The rest 45 cases were divided into two groups according to whether they received intrauterine interventions or not, the intrauterine intervention group (n=18) and the control group (n=27), and the clinical characteristics and pregnancy outcomes were compared. Independent samples t-test or Kruskal-Wallis test, Chi-square test or Fisher exact test were applied for statistical analysis. Results The mean gestational age of the intervention group at diagnosis of NIHF was lower than that of the control group [26.5(23.4-30.0) weeks vs 30.3(29.0-32.0) weeks, χ2=7.427, P=0.006]. Compared with the control group, the intrauterine fetal death rate was slightly lower [25.9％(7/27) vs 1/18], the neonatal survival rate was slightly higher [37.0％(10/27) vs 11/18] in the intrauterine intervention group, although no statistically significance was observed (Fisher exact, P>0.05). In the intrauterine intervention group, the incidence of low Apgar score (<4) at both 1 and 5 min was 1/17 and 0/17, respectively, which was much lower than those of the control group [45％(9/20) and 35％(7/20), Fisher exact, both P<0.05]. Conclusions After overall prenatal evaluation, appropriate intrauterine interventions may improve the pregnancy outcomes in NIHF.

Perinatal outcomes of thoraco-amniotic shunting for severe primary fetal hydrothorax / 中华妇产科杂志

Objective To evaluate the safety and perinatal outcomes of thoracoamniotic shunting in the treatment of fetuses with severe primary hydrothorax. Methods 22 cases of suspected severe primary fetal hydrothorax which underwent thoraco-amniotic shunting in Shanghai First Maternity and Infant Hospital,Fetal Medicine Unit and Prenatal Diagnosis Center from January 2012 to December 2017 were analyzed retrospectively. Hydrothorax associated with structural or chromosomal abnormalities, infections and immune fetal hydrops were excluded. Results Totally ,28 shunts were placed in 22 fetuses. The median gestational age at TAS was 31.3 weeks. Preterm membrane rupture within 7 days after the procedure occurred in 9.1％(2/22) cases. Catheter displacement occurred in 18％(4/22) cases. The interval from shunting to delivery was 26.0 days. One fetus ended in induced abortion; 21(95％,21/22) babies were born alive, and their median gestational age at delivery was 34.4 weeks. 62％(13/21)newborns required ventilator supports; 4 neonatal deaths were attributed to pulmonary hypoplasia. The overall perinatal survival rate was 81％(17/21). The perinatal survival rate with hydrops and without hydrops were 10/13 and 7/8 respectively. Conclusion Thoraco-amniotic shunting is a safe procedure for intrauterine therapy and could improve the perinatal outcomes of severe primary fetal hydrothorax.

Comparison of short-term therapeutic effect and prognosis between levosimendan and milrinone on pa-tients with decompensated heart failure / 心血管康复医学杂志

Objective:To observe short-term therapeutic effect and prognosis of levosimendan or milrinone on patients with decompensated heart failure(DHF).Methods:A total of 120 DHF patients treated in our hospital were equal-ly divided into levosimendan group(received levosimendan based on routine anti-HF treatment)and milrinone group (received milrinone based on routine anti-HF treatment),both groups were treated for one week continuously.Lev-el of brain natriuretic peptide(BNP),left ventricular ejection fraction(LVEF)and 6min walking distance(6MWD) were compared between two groups before and after treatment.Results:Compared with before treatment,on one week after treatment,there was significant reduction in BNP level and significant rise in LVEF in two groups,P=0.001 all;compared with milrinone group after one-week treatment,there was significant reduction in BNP level [(224.45 ± 29.45)pg/ml vs.(197.41 ± 27.65)pg/ml]and significant rise in LVEF[(37.72 ± 2.03)% vs.(44.33 ± 1.94)%]in levosimendan group,P=0.001 both.Compared with before treatment after three-month treatment, there was significant rise in 6MWD in two groups(P=0.001),and 6MWD of levosimendan group was significantly longer than that of milrinone group[(441.76 ± 75.45)m vs.(409.63 ± 73.56)m],P=0.02. Conclusion:Short-term therapeutic effect and prognosis of routine anti-HF medication combined levosimendan are significantly better than those of combined milrinone treatment in DHF patients.

Detection of disease-causing gene in a Hui congential cataract pedigree by exon combined target region capture sequencing chip / 中华实验眼科杂志

Background Congenital cataract is an important cause of blindness and amblyopia in children,and about 50％ of congenital cataract is hereditary.Objective The aim of this study was to determine the diseasecausing gene of one Hui congenital cataract pedigree by using exon combined target region capture sequencing chip of eye diseases.Methods This study was approved by Ethic Committee of Ningxia People's Hospital and followed Declaration of Helsinki.One Hui congenital cataract pedigree was recruited in Ningxia Eye Hospital in 2011.All the disease history of the members in this family were collected and recorded,and the eye examinations were performed.The peripheral blood specimens were collected from family members and 300 healthy individuals for the extraction of DNA.Exon combined target region capture sequencing chip of eye diseases was used to screen the candidate diseasecausing mutations,then PCR and direct sequencing were used to confirm the disease-causing mutations.Results This H ui family included 61 members of 6 generations,and 18 patients were diagnosed in serial 5 passages,conforming to autosomal dominant inheritance pattern.Among 18 cataract patients,7 individuals were associated with nystagmus and strabismus,and 4 patients had high myopia.Eight candidate pathogenetic mutations were detected by exon combined target region capture sequencing chip of eye diseases and bioinformatics method,with 5 mutations in noncoding regions and 3 in coding regions.The mutation P24T of CYRGD gene was confirmed as pathogenic mutation of this pedigree by using PCR and direct sequencing methods.These mutations co-segregated with affected members of the family,and the mutations were not found in the unaffected family members and 300 unrelated controls.Conclusions P24T of CYRGD gene mutation is confirmed as pathogenic mutation of this pedigree.Exon combined target region capture sequencing chip provides a new approach to detect disease-causing mutations of congenital cataract with diversity clinical phenotypes.

Monochorionic monoamniotic twin pregnancy: a review of 17 cases / 中华围产医学杂志

Objective To review the diagnosis,monitoring,management and perinatal outcomes of monochorionic monoamniotic (MCMA) twin pregnancy.Methods From July 2010 to August 2013,there were 17 MCMA twin pregnancies diagnosed and delivered in Shanghai First Maternity and Infant Hospital.According to the MCMA management protocol,induced abortion,elective fetal reduction,and anticipant pregnancy were optional.For those anticipant pregnancies,fetal lung underwent maturation promotion at gestational weeks 28; hospitalization with 40 min/day continual fetal electronic monitoring and umbilical blood monitoring twice weekly at gestational weeks 28-30; 40 min continual fetal electronic monitoring twice daily and umbilical blood monitoring once every other day at gestational weeks 30-32; and 40 min continual fetal electronic monitoring three times daily and umbilical blood monitoring once daily at gestational weeks 32-34; and pregnancy ended on time.The presence of umbilical cord entanglement,congenital malformation,intrauterine fetal death,complications exclusive to monochorionic twins (e.g.selective fetal growth restriction,twin reversed arterial perfusion sequence and twin-twin transfusion syndrome) and the perinatal outcomes were retrospectively analyzed.Results Average maternal age of women with 17 MCMA twins was (29.0±2.7) years,and all were primiparas.They were diagnosed at (18.6± 5.5) weeks on average (11 +5-28+1 weeks).Umbilical cord entanglements were detected in all cases by ultrasonography and confirmed postnatally.There were three cases of complications specific to monochorionic twins,including two with selective fetal growth restriction and one with twin reversed arterial perfusion sequence.There were seven women with fetal congenital malformation; four of whom chose induced abortion; one case of anencephaly chose radiofrequency ablation fetal reduction,and the remaining two cases with congenital malformation and ten cases without chose anticipant pregnancy,and there were no abnormal ultrasonography signs during pregnancy.Among these 12 cases,intrauterine fetal death of both fetuses occurred in two cases at 16 and 21+1 weeks gestation and they were aborted.Intrauterine fetal death of a single fetus occurred in one case at 30+2 weeks gestation (another fetus was delivered by emergency cesarean section).There were a total of eleven live births delivered by cesarean section (four by emergency cesarean section) at a median gestational age of (32.7± 1.6) weeks.There were 20 live neonates with a mean birth weight of (1 850±496) g.Sixteen neonates were transferred to the neonatal intensive care unit and hospitalized for (37.9± 16.4) days.Nine neonates suffered from respiratory distress syndrome but were eventually cured.Conclusions MCMA twin pregnancy has high morbidity and mortality.Early ultrasonography helps to clarify the diagnosis and enhance the monitoring,thus improving the perinatal outcomes.

Perinatal outcomes following selective feticide by radiofrequency ablation in complex monochorionic ;pregnancies / 中华围产医学杂志

To assess the perinatal outcomes following selective feticide through radiofrequency ablation (RFA) in complex monochorionic pregnancies. Methods In this retrospective observational study, 34 cases of complex monochorionic pregnancies treated with RFA for selective feticide and delivered at the Shanghai First Maternity and Infant Hospital between January 1, 2012 and December 31, 2013, were included. Gestational age at RFA, the number of RFA cycles, maternal and fetal complications, gestational age at delivery, neonatal outcomes at 28 days after birth and neonatal development after birth were recorded. Fetal survival rate were defined as the number of survivors at 28 days after birth divided by the number of remaining fetuses after RFA. Factors affecting fetal survival rate were also analyzed. Statistical analysis was performed using Fisher's exact test. Results (1) The process for RFA:The gestatinal age for the procedure was (20.7±3.1) weeks(16+1-27+6 weeks). The successful rate of procedures was 100%(34/34) and the cycle number for RFA was 1-6 times. (2)Fetal complications and survival rate of remaining fetuses after RFA:there were six pregnant women suffering from premature rupture of membrane (PROM) before 28 weeks. Among those women, one had miscarriaged at 25 weeks, one chose to terminate at 26 weeks and the remaining four chose to continue the pregnancy. There were three remaining fetuses developing fetal severe anemia with hydrops after RFA. Two of them had fetal demises 2 days after the procedures and one chose to have termination. Another two cases with discordant fetal anomalies had fetal demises with unknown reasons one day after RFA. There were 27 remaining fetuses after RFA who survived until 28 days after birth. The mean gestational age at delivery was(36.4±4.1)weeks (26+4-40 weeks) and the mean birth weight was (2 913± 978) g (1 080-4 600 g). The overall fetal survival rate 28 days after birth was 79%(27/34). There were no abnormal findings in antenatal magnetic resonance imaging (MRI) four weeks after the procedure and no abnormal development of nervous system in the surviving neonates between 3 months old and 1.5 years old. (3) Factors affecting fetal survival rate :There were no significant differences identified in the rate of fetal severe anemia and fetal demise (2/15, 2/13 and 1/6), the rate of PROM before 28 weeks (1/15, 4/13 and 1/6) and survival rate of 28 days after birth (13/15, 10/13 and 4/6)among three groups with different gestational age (16+1-, 20- and 24-27+6 weeks) for RFA(all P>0.05). The indications for RFA included severe selective intrauterine growth restriction (50%, 17/34), discordant for fetal abnormalities(24%, 8/34) , twin reversed arterial perfusion sequence(18%, 6/34)and dichorionic or monochorionic triamniotic pregnancy (9%, 3/34). There were also no significant differences noted in the rate of fetal complications and fetal demise(3/17, 2/8, 0/6, 0/3), the rate of PROM before 28 weeks (3/17, 0/8, 2/6, 1/3)and survival rate of 28 days after birth among different groups (12/17, 6/8, 6/6, 3/3) with different indications for RFA(all P>0.05) . No significant differences observed in the rate of fetal complications and fetal demise(10% and 2/5)and the rate of PROM before 28 weeks (17%and 2/5)between two groups with different cycle numbers for RFA (<3 times and≥3 times, all P<0.05), while the group with cycle number ≥ 3 times had lower survival rate 28 days after birth than the group with cycle number<3 times for RFA (2/5 vs 86%, P<0.05). Conclusions RFA is one of effective and safe procedures for selective feticide in complex monochorionic pregnancies.

Placental characteristics in uncomplicated monochorionic diamniotic twin pregnancies / 中华围产医学杂志

Objective To investigate the association between placental sharing,vascular anastomoses,cord insertion and perinatal outcome in uncomplicated monochorionic diamniotic (MCDA) placentas.Methods Between January 1,2012 and July 31,2013,60 uncomplicated (seclective fetal growth restriction,twin anemia-polycythemia sequence and twin-twin transfusion dyndrome) MCDA placentas were studied.These uncomplicated MCDA placentas were divided into the placenta equally shared group with placental territory discordance (PTD) ＜0.25 and the placenta unequally shared group with PTD ≥ 0.25.Angioarchitecture,cord insertion type and the distance between two cord insertions were compared using the Chi-square test and nonparametric test.Results Mean maternal age was (30.3±4.1) years.There were 39 cases (65％) in the placenta equally shared group and 21 (35％) in the placenta unequally shared group.Vascular anastomoses were observed in all placentas,arterioarterial anastomoses in 58 placentas (97％),and venovenous anastomoses in 17 placentas (28％).The overall diameter and the maximum diameter of arterioarterial anastomoses in the placenta equally shared group were (0.19±0.11) cm and (0.18±0.09) cm,respectively,and were lower than those in the placenta unequally shared group [(0.27±0.11) cm and (0.27±0.12) cm,respectively] (T were-2.39 and-2.94,P＜0.05,respectively).No significant differences in the number,the overall diameter and the maximum diameter of venovenous anastomoses were observed between the two groups (all P＞0.05).The incidence of cord velamentous insertion and cord velamentous insertion plus cord marginal insertion were 14％ (11/78) and 42％ (33/78),respectively,in the placenta equally shared group,and were similar to those in the placenta unequally shared group [14％ (6/42) and 33％ (14/42),x2 were 1.00 and 0.43,P＞0.05,respectively].The mean distance between two cord insertions was shorter in the placenta unequally shared group than in the placenta equally shared group [(14.3±6.3) cm vs (18.2±6.0) cm,T=2.37,P＜0.05].Conclusions In cases with unequally shared placenta,the distance between two cord insertions is shorter and the diameter of arterioarterial anastomoses is larger,which may compensate for their unequal placental territories,leading to no complications in these MCDA twin.