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Objective To evaluate the clinical value of free glycoprotein non-metastatic melanoma protein B(GPNMB)as a drug resis-tance and prognostic marker for non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)amplifica-tion accompanied by mutations.Methods Fifty-five cases of NSCLC patients with EGFR amplification associated with mutations who received treatment from March 2018 to September 2019 were included as the observation group.All patients received an EGFR-tyrosine kinase inhibitor(EGFR-TKI)as the first-line treatment;67 blood samples from the physical examination center during the same period were randomly included as healthy control.We compared the expression levels of free GPNMB between the two groups,explored the correlation between GPNMB expression and the clinicopathological information in the observation group;and combined the clinical efficacy to evaluate its value as a drug resistance marker.Through follow-up,the progress free survival(PFS)of patients was statistically analyzed,and through multivariate Cox regression analysis,independent risk factors affecting the survival in the observation group were explored.Results Compared with that in the control group,the expression level of free GPNMB in the observation group was signi-ficantly up-regulated.The expression level of free GPNMB in the observation group is significantly related to the clinical efficacy of EGFR-TKI(P = 0.016).Patients with high GPNMB expression have significantly stronger drug resistance,and patients with high GPNMB expression have significantly shorter PFS duration(P = 0.032).A high free GPNMB expression(HR = 4.029,95%CI:1.942-8.358,P＜0.001)is also an independent risk factor affecting patient survival.Conclusion The expression level of free GPNMB in patients with EGFR amplification accompanied by mutant NSCLC is significantly up-regulated,and its high expression is significantly related to the enhancement of the patient's drug resistance.High GPNMB expression is significantly related to the poor prognosis of patients and is an independent risk factor affecting patient survival.
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Objective To observe the effects of Huatan Quyu Decoction on cognitive function and the expressions of GABA and VILIP-1 in brain tissue of rats with cerebral small vessel disease;To discuss its mechanism for treatment on cerebral small vessel disease.Methods Totally 48 male SD rats were randomly divided into blank group,model group,Huatan Quyu Decoction low-and high-dosage groups,with 12 rats in each group.Except for the blank group,a rat model of cerebral small vessel disease was prepared by in vitro injection of homologous microemboli.Huatan Quyu Decoction low-and high-dosage groups were given Huatan Quyu Decoction 1.25 and 2.5 g/kg by gavage,the blank group and model group were gavage with equal amounts of distilled water for 28 consecutive days.Morris water maze experiment was conducted on day 1,7,14,and 28 after administration to evaluate the learning and memory abilities of rats,HE staining was used to observe pathological changes in hippocampal tissue,and immunohistochemical staining was used to detect the expressions of GABA and VILIP-1 proteins in brain tissue.Results Compared with the blank group,the escape latency of Morris water maze experiment in model group significantly prolonged(P<0.05),and the number of crossing platforms was significantly reduced(P<0.05);the arrangement of hippocampal tissue cells was disordered,gaps widen,and nuclei atrophy and necrosis,the GABA expression in brain tissue significantly decreased(P<0.05),while the VILIP-1 expression significantly increased(P<0.05).Compared with the model group,the escape latency of Morris water maze experiment in the Huatan Quyu Decoction low-and high-dosage groups significantly shortened(P<0.05)on day 7,14,and 28 of administration,and the number of crossing platforms significantly increased(P<0.05),GABA expression significantly increased(P<0.05),while VILIP-1 expression significantly decreased(P<0.05).Compared with the Huatan Quyu Decoction low-dosage group,the escape latency of Morris water maze experiment in Huatan Quyu Decoction high-dosage group decreased at various time points,and the number of crossing platforms increase,the pathological damage of hippocampal tissue was reduced,the expression of GABA in brain tissue increased,and the expression of VILIP-1 decreased,with statistical significance(P<0.05).Conclusion Huatan Quyu Decoction can increase the expression of GABA in brain tissue and inhibit the expression of VILIP-1,thereby improve the cognitive function of rats with cerebrovascular disease.
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Objective:To investigate the expression level of transcription factor dimerization partner 2 (TFDP2) in the placentas of women with preeclampsia, and analyze its effect on the apoptosis of trophoblast cells.Methods:Placental tissues from thirty puerperae with preeclampsia who gave birth by cesarean section in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School between January 2018 and December 2022 (preeclampsia group) and 30 healthy puerperae undergoing cesarean section during the same period (control group) were retrospectively selected. Immunohistochemistry was used to localize TFDP2 in the placental tissues. Real-time quantitative-polymerase chain reaction (qRT-PCR) and Western blot were used to detect the differences in expression of TFDP2 at mRNA and protein levels in placental tissues between the two groups. Forskolin-exposed BeWo cells were transfected with small interfering RNA (siRNA) to knockdown TFDP2 and the changes in the expression of apoptosis-related indicators, B cell lymphoma 2 (Bcl2) and Bcl2 associated X (Bax), at protein and mRNA levels were analyzed by Western blot and qRT-PCR, respectively. Besides, the change in the apoptosis level of BeWo cells was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and flow cytometry. Downstream signaling pathways were analyzed to understand the involved molecular mechanisms. Two independent samples t-test, Wilcoxon rank-sum test, and Chi-square test were used for statistical analysis. Results:TFDP2 was mostly localized in the syncytiotrophoblasts and the extravillous trophoblasts in the normal placentas. TFDP2 expression in the syncytiotrophoblasts was lower in the preeclampsia group than in the control group at both mRNA (0.722±0.239 vs. 1.000±0.348, t=3.61, P=0.001) and protein (0.728±0.185 vs. 1.000±0.206, t=2.41, P=0.037) levels. Comparing the group without knockdown of TFDP2, the knockdown of TFDP2 in BeWo cells elevated the Bax/Bcl2 ratio (mRNA: 1.755±0.452 vs. 1.000±0.279, t=3.48, P=0.006; protein: 3.206±0.922 vs. 1.000±0.290, t=3.95, P=0.017), and increased cell apoptosis both in number and ratio (TUNEL staining: 4.556±1.740 vs. 2.444±1.130, t=3.05, P=0.008; flow cytometry: 21.37%±1.66% vs. 12.61%±0.38%, t=8.92, P=0.001). Furthermore, following TFDP2 knockdown, a decrease in the phosphorylation activity of catalytic subunit of protein kinase A (PKAc) at the Thr197 site was observed in the cytoplasm of BeWo cells (0.466±0.035 vs. 1.000±0.075, t=11.19, P<0.001) and a reduction in the expression of β-catenin in the cell nucleus was also detected (0.250±0.093 vs. 1.000±0.269, t=4.57, P=0.010). Conclusion:The expression of TFDP2 decreased significantly in the placentas of patients with preeclampsia, which may promote the apoptosis of syncytiotrophoblasts by inhibiting the PKAc/β-catenin signaling pathway.
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The lower limit of preterm birth varies around the world. In China, the lower limit of preterm infants is set at the gestational age of 28 +0-36 +6 weeks or birth weight ≥1 000 g. Extremely preterm infants are defined as neonates born before 28 weeks of gestation by the World Health Organization. With the development of perinatal medicine and the achievements in neonatal care, the survival rate and the short/long-term outcomes of extreme preterm infants have been greatly improved in China. This article reviews the survival rate, mortality/severe disability rate and medical costs of extremely preterm infants, aiming to provide reference for setting the right lower limit of gestational age for preterm births.
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Objective To determine the effect of crocin regulating miR-139-5p/ATF4 axis on myo-cardial injury and energy metabolism in rats with CHF.Methods A total of 84 male SPF SD rats were randomly divided into sham operation group,model group,crocin low-,medium-and high-dose groups,captopril group and crocin+miR-139-5p inhibitor group,with 12 in each group.Car-diac function indexes,myocardial histomathological morphology,apoptotic rate,myocardial injury indexes,heart failure indexes,inflammatory indexes,oxidative stress indexes,myocardial ATP content,SDH activity,and miR-139-5p and ATF4 mRNA expression levels were detected in rats.The targeting relationship between miR-139-5p and ATF4 was verified.Results Compared with the conditions in the model group,crocin treatment at different doses reduced apoptotic rate of cardiomyocytes,decreased MDA content,LVEDD and LVESD values and cTnI,cTnT,CK-MB,NT-proBNP,TNF-α and IL-1β levels,and declined ATF4 mRNA level,and increased LVEF and LVFS values,SOD activity,ATP content,SDH activity and miR-139-5p level(P＜0.05).Com-pared with the crocin high-dose group,the crocin+miR-139-5p inhibitor group had higher apop-totic rate of cardiomyocytes[(22.68±3.25)％vs(11.94±1.38)％,P＜0.05],increased LVEDD and LVESD value,raised MAD content and cTnI,cTnT,CK-MB,NT-proBNP,TNF-α and IL-1βlevel,and elecated ATF4 mRNA level,and decreased LVEF and LVFS value,SOD activity,ATP content,SDH activity and miR-139-5p level(P＜0.05).There was a targeting relationship be-tween miR-139-5p and ATF4.Conclusion Crocin can improve myocardial injury and energy me-tabolism in CHF rats,which may be related to its regulation of miR-139-5p/ATF4 axis.
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The high incidence of preterm birth is one of the great challenges for the survival, especially for the high-quality survival, of offspring. This paper reviews and prospects the prevalence of premature birth in China, the definition of the lower limit of the gestational week of premature birth, the high-risk factors and the prophylaxis. It is suggested that relevant research should be carried out actively, such as specific high-risk factors of premature birth, screening for shortened cervical length, vaginal progesterone, and oral aspirin to prevent premature birth, etc. It also appeals to all the perinatal medical workers to make joint efforts for the improvement of the survival rate of premature infants and reduction of the major disability rate in China.
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Objective:To explore the clinical significance of cervical length (CL) measured by transabdominal ultrasound during fetal structural anomalies screeing at 20-24 +6 weeks of gestation. Methods:This was a retrospective nested case-control study based on a prospective longitudinal cohort of "Prediction and Prevention of Early-onset Preeclampsia", which recruited 4 995 singleton pregnant women at the gestational age of 11-13 +6 weeks in Nanjing Drum Tower Hospital from April 2019 to August 2022. All the subjects underwent second-trimester ultrasound screening for fetal structural anomalies in our hospital with image records. This study excluded the women who were lost to follow-up, underwent cervical cerclage, terminated the pregnancy due to personal or social factors, or had miscarriage before 20 weeks of gestation, and those with iatrogenic preterm births, intrauterine fetal death or no second-trimester cervical sonography images. Propensity score matching was used to match pregnant women with spontaneous preterm birth ( n=101) and those with full-term delivery ( n=101) in a 1∶1 ratio, with factors of maternal age, body mass index, preterm birth history, cesarean section history, and pregnancy interval ≥5 years. CL was measured based on the retained ultrasound images. Nonparametric test or Chi-square test were used for statistical analysis. Receiver operating characteristic (ROC) curve was used to evaluate the correlation between CL measured by transabdominal ultrasound in the second trimester and spontaneous preterm birth. Results:The CL measured by transabdominal ultrasound at 20-24 +6 weeks of gestation was significantly shorter in the spontaneous preterm birth group than that in the full-term group [2.8 cm (2.5-3.3 cm) vs. 3.4 cm (3.0-3.9 cm), Z=－5.85, P<0.001]. If CL<3.4 cm was used as the cut-off value for predicting spontaneous preterm birth (20-36 +6 weeks), the specificity and the sensitivity were 0.50 and 0.77, respectively, and the sensitivity reached 0.92 for predicting preterm birth before 32 weeks and 1.00 for predicting preterm birth before 28 weeks. If CL<3.7 cm was used as the cut-off value, the specificity and the sensitivity were 0.36 and 0.87, respectively, and the sensitivity was 1.00 for predicting preterm birth before 32 weeks. The efficacy of preterm birth screening at 28-36 +6 weeks of gestation was comparable to that at 20-36 +6 weeks, if CL<3.4 cm and CL<3.7 cm were used as the cut-off value, the sensitivity were 0.76 and 0.86, respectively. Conclusion:Transabdominal ultrasound measurement of CL in the second trimester can be a preliminary screening to determine whether further transvaginal ultrasound measurement of CL is needed for women without a history of preterm birth or late spontaneous abortion.
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Objective:To analyze the epidemiological characteristics of geriatric hip fractures.Methods:This study retrospectively analyzed the clinical characteristics of 2 054 elderly patients with hip fracture aged 60 years and over who were admitted to Beijing Hospital from January 2011 to December 2020.The epidemiological characteristics of geriatric hip fractures were analyzed from the aspects of age, gender, fracture type, length of stay, surgical method and surgical complications.Results:The total number of hip fractures patients admitted from 2011 to 2020 showed a general upward trend in quantity.Among them, there were 1 177 femoral neck fractures(57.3%, 1 177/2 054), and 877 intertrochanteric femoral fractures(42.7%, 877/2 054)with statistical differences in the distribution of fracture types between patients at different ages( χ2=61.727, P<0.001). A total of 1 839 patients chose surgical treatment, accounting for 89.5% of the total number of patients.Artificial femoral head arthroplasty was the most common operation mode for patients with femoral neck fractures(783 cases, 75.4%).534 patients with intertrochanteric femoral fractures(66.8%)were treated with closed reduction and femoral intramedullary nailing.There was a statistically significant difference in operation modes among different fracture types( χ2=1 480.800, P<0.001). The length of hospital stay in patients with femoral neck fracture was(14.2±8.3)days, which was significantly longer than in patients with femoral neck fracture(13.2±10.9)days( t=2.417, P=0.016). There was no significant difference in the time from admission to operation between the two groups[(5.7±3.5)days vs.(5.4±3.3)days]( t=1.954, P=0.051). Among all the comorbidities of hip fracture patients, the top 5 diseases were cardiovascular system diseases(2 001 cases, 97.4%), nervous system diseases(1 105 cases, 53.8%), endocrine system diseases(814 cases, 39.6%), skeletal and muscular system diseases(623 cases, 30.3%), digestive system diseases(472 cases, 23.0%).1 485 patients(72.3%)had 3 or more comorbidities. Conclusions:Hip fractures in the elderly have some epidemiological distribution characteristics in terms of age, gender, length of hospitalization, injury mechanism and comorbidities, which is conducive to further improve the prevention and treatment strategies for hip fractures and promote the rational allocation of medical resources.
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Objective:To evaluate the performance of biomarkers in aneuploidy screening in the first trimester-pregnancy associated plasma protein A(PAPP-A) combined with Fetal Medicine Foundation (FMF)'s competing risk model in screening preeclampsia among our population.Methods:This study was based on a prospective cohort of singleton pregnant women who underwent aneuploidy screening in the first trimester in Nanjing Drum Tower Hospital from January 2017 to September 2020. Mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and PAPP-A were converted into multiples of median (MoM) using the algorithm disclosed on the website of the FMF (fetalmedicine.org). The predictive outcomes of maternal factors alone or in combination with MAP, UtA-PI, and PAPP-A (alone or in combination) were calculated. Chi-square test, Fisher's exact test or rank sum test were used for comparison among groups and Bonferroni method for pairwise comparisons. Receiver operating characteristic (ROC) curve was used to evaluate the screening efficiency and to calculate the sensitivities of predicting preeclampsia, term and preterm preeclampsia at false-positive rates of 5% and 10%. The predictive performance of this model was further compared to the screening strategy that was recommended in Diagnosis and treatment of hypertension and pre-eclampsia in pregnancy: a clinical practice guideline in China (2020). Results:Among the 5 144 singleton pregnancy women who were recruited in the cohort, 4 919 cases were included and analyzed in this study. A total of 223 cases were diagnosed as preeclampsia (4.5%), including 55 preterm (1.1%) and 168 term preeclampsia (3.4%). The median of MoM values of MAP, UtA-PI, and PAPP-A in the non-preeclampsia group were around 1.0±0.1. Statistical significance was observed in the difference of MAP, UtA-PI, and PAPP-A Mom between women with preterm preeclampsia and those without preeclampsia [1.061 (0.999-1.150) vs 0.985 (0.935-4.043), 1.115 (0.873-1.432) vs 1.039 (0.864-1.236), 0.820 (0.493-1.066) vs 1.078 (0.756-1.508)], which was also seen in the difference of MAP and PAPP-A Mom between women with term preeclampsia and those without preeclampsia [1.065 (1.002-1.133) vs 0.985 (0.935-4.043), 1.007 (0.624-1.393) vs 1.078 (0.756-1.508)] (all P<0.025). The combination screening with maternal factors+MAP+UtA-PI+PAPP-A was noted for the best efficiency. In predicting preeclampsia preterm and term preeclampsia at the false-positive rate of 10%, the sensitivity of the model was 53.0%, 76.4% and 44.6% respectively. Using the screening method recommended in Diagnosis and treatment of hypertension and pre-eclampsia in pregnancy: a clinical practice guideline in China(2020), the proportion of people at high risk of preeclampsia was 5.9% (290/4 919), and the sensitivity for predicting preterm preeclampsia was 25.5% (14/55), which was significantly lower than the combination screening with maternal factors+MAP+UtA-PI+PAPP-A [65.5% (36/55)] when using the same proportion of high-risk population. Conclusion:The preeclampsia screening model based on aneuploidy screening biomarkers in the first trimester--PAPP-A in combination with materral factors, MAP, UtA-PI, can effectively screen preterm preeclampsia in the local population without increasing the laboratory costs.
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Objective:To understand the actual situation of the implementation of “Diagnosis and therapy guideline of preterm birth（2014）”, “Guideline” for short, by front-line obstetricians, and to provide reference for the further update and supplement of the “Guideline”.Methods:This study designed a structured questionnaire for the prominent problems in the prevention and treatment of preterm birth, which was determined by the expert team drafting the “Guideline”. In October to November 2021, a cross-sectional survey was conducted among obstetricians, including members of the Perinatal Medicine Branch of Jiangsu Medical Association and the Obstetrics Subgroup,Chinese society of Obstetrics and Gynecology, Chinese Medical Association, on the implementation status of the “Guideline”. The recommendations of the “Guideline” were used as standard answers to determine the implementation rate. A total of 328 valid questionnaires were collected. The total score of the questionnaire was 12 points. The questionnaire was divided into low executive ability group (<7 points) and high executive ability group (≥7 points) with a score of 7 as the threshold value, and the differences in baseline information such as hospital grade and professional title between the two groups were compared.Results:The score of 328 obstetricians was (7.6±1.6) points, including 250 (76.2%, 250/328) in the high execution group and 78 (23.8%, 78/328) in the low execution group. The execution rates of “the use of uterine contraction inhibitors for short courses”[97.0% (318/328)], “late umbilical cord breakage after birth of premature infants”[87.8% (288/328)] and “should preterm patients with intact membranes be treated with antibiotics”[86.6% (284/328)] were all over 80%, indicating good implementation. Multiple logistic regression analysis showed that hospital grade and professional title were independent factors influencing the performance of the “Guideline”(all P<0.05), and secondary hospitals had lower scores and worse execution than tertiary hospitals ( OR=0.42, 95% CI: 0.23-0.77; P=0.005). Senior titles had higher scores and better execution than junior titles ( OR=5.33, 95% CI: 2.35-12.07; P<0.001). When answering the question “gestational week at which premature infants could survive in your hospital”, only 3.4% (11/328) answered 22 weeks, and 44.5% (146/328) answered 28 weeks, accounted for the highest proportion. The gestational week of surviving premature infants in tertiary hospitals was earlier than that in secondary hospitals ( P<0.05). The gestational week of surviving premature infants answered by senior titles was earlier than that of junior titles ( P<0.05). Conclusions:Obstetricians generally have a good implementation of the “Guideline”, and their understanding of some recommended clauses in the guidelines needs to be improved. In the future, training of primary hospitals and physicians with junior titles should be strengthened.
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More and more new technologies are being applied to prenatal diagnosis as the development of genetic testing technology advances. Pedigree analysis and phenotype recognition are the foundation of prenatal genetic counseling and diagnosis. In addition, fully understanding the advantages and disadvantages of different genetic testing techniques, developing a rationale, standardized and sequential testing strategy for the affected family, and analyzing the underlying genetic etiology and prognosis are critical for prenatal diagnosis and achieving the goal of birth defect prevention.
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Objective:To construct the gestational‐age‐specific blood pressure curve and percentile blood pressure values of pregnant women in Jiangsu Province, and to explore the clinic significance of the blood pressure changes in women whose blood pressure was less than 140/90 mmHg (1 mmHg=0.133 kPa) in each trimester and eventually developed pregnancy induced hypertension (PIH) or pre-eclampsia (PE).Methods:A prospective longitudinal cohort during pregnancy was built. Singleton pregnant women in the first trimester (11-13 +6 weeks) were recruited from July 2017 to September 2020 in Nanjing Drum Tower Hospital, and were followed up in the second trimester (19-23 +6 weeks), the third trimester (30-33 +6 weeks) and approaching the expected date of delivery (35-38 +6 weeks). The Viewpoint 6.0 software was used to record pregnancy-related information. The blood pressure was measured by standard methods in our clinic. Least mean square (LMS) function was performed to fit the gestational-age-specific blood pressure curve and percentile blood pressure values were calculated at every follow‐up time point. Logistic regression was applied to calculate the OR for the groups with blood pressure ≥95th percentile ( P95). Results:There were 3 728 singleton pregnant women invited in this study, including 3 490 normal pregnant women (93.62%, 3 490/3 728), and 238 pregnant women with PIH or PE (6.38%, 238/3 728). Gestational-age-specific blood pressure curve showed that systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) decreased in the second trimester, compared with those in the first and the third trimester, however the fluctuation of blood pressure was low, but regardless of the gestational age, P95 of SBP, DBP and MAP increased by 14, 11 and 11 mmHg respectively, compared with 50th percentile ( P50). In the first trimester, the risk of developing PIH or PE finally in pregnant women with blood pressure ≥ P95 was 4.36-fold (95% CI: 2.99-6.35) for SBP than women with SBP< P95, 5.22-fold (95% CI: 3.65-7.46) for DBP and 5.14-fold (95% CI: 3.61-7.32) for MAP. When approaching the expected date of delivery, the corresponding risks of the women with blood pressure ≥ P95 were 16.76 times, 27.45 and 27.31 times respectively than those of the women with blood pressure < P95. In the first trimester, every 1 mmHg elevation of SBP the risk developing PIH or PE increased by 24% ( OR=1.24, 95% CI: 1.15-1.33), 44% ( OR=1.44, 95% CI: 1.31-1.59) for DBP and 47% ( OR=1.47, 95% CI: 1.33-1.61) for MAP, respectively. The risk in the second trimester was similar to that in the first trimester, and in the third trimester, the risk was further increased. When approaching the expected date of delivery, DBP or MAP increased by 1 mmHg, the risk developing PIH or PE was double; while SBP increased by 1 mmHg, the risk increased by 58%. The areas under the receiver operator characteristic curves of SBP, DBP and MAP were similar for predicting PIH or PE, and the predictive efficiency were all poor. Conclusions:Construction of percentile blood pressure values for pregnant women is helpful in identification of high-risk women of developing PIH or PE. The risk of PIH or PE in pregnant women with blood pressure ≥ P95 but <140/90 mmHg has significantly increased compared with women with blood pressure < P95.
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Objective:To investigate the effects of gestational weight gain (GWG) at different stages on pregnancy complications such as preeclampsia, gestational hypertension, gestational diabetes mellitus(GDM), small for gestational age (SGA), and large for gestational age (LGA).Methods:This was a prospective longitudinal cohort study. Singleton pregnancies at 11-13 +6 weeks of gestation in the Affiliated Drum Tower Hospital, Medical School of Nanjing University from January 2017 to November 2019 were recruited. The maternal height, weight, blood pressure, and fetal ultrasonic parameters were measured at 19-23 +6, 29-34 +6, and 35-40 +6 weeks of gestation by face-to-face interview and the pregnancy outcomes were followed up. All participants were grouped by body mass index (BMI) in the first trimester, with <18.50 kg/m 2 as underweight group, 18.50-23.99 kg/m 2 as normal group, ≥24.00 kg/m 2 as overweight/obesity group. Chi-square test and rank-sum test were adopted for comparison among groups. Weekly weight gain was converted into Z scores, and insufficient, appropriate, and excessive weight gain were respectively defined when Z<-1, -1≤ Z≤1, and Z>1. The effect of weekly weight gain at different gestational trimesters on pregnancy complications was analyzed by binary logistic regression. Results:Totally, 4 143 pregnant women entered the cohort. After excluding 327 cases, 3 816 were finally included in the analysis, with 394 in underweight group, 2 668 in normal group, and 754 in overweight/obesity group. Excessive weekly weight gain in the early second trimester was a risk factor for LGA( aOR=1.78, 95% CI:1.31-2.42, P<0.001), and in the later second trimester it was associated with preterm preeclampsia ( aOR=3.00, 95% CI: 1.26-7.10, P=0.013), gestational hypertension ( aOR=2.38, 95% CI: 1.44-3.94, P=0.001), and LGA ( aOR=1.59, 95% CI: 1.15-2.22, P=0.005). In the third trimester, excessive weekly weight gain was associated with higher risks of term preeclampsia ( aOR=2.70, 95% CI: 1.61-4.54, P<0.001) and gestational hypertension ( aOR=1.84, 95% CI: 1.05-3.21, P=0.033); while insufficient weekly weight gain was a risk factor for SGA ( aOR=1.58, 95% CI: 1.01-2.48, P=0.045), but a protective factor for term preeclampsia ( aOR=0.37, 95% CI: 0.14-0.97, P=0.041). Insufficient and excessive weekly weight gain in the early second trimester were not related to GDM (both P>0.05). Conclusions:GWG at different stages has different effects on pregnancy complications. A more relaxed control of GWG in the early second trimester combined with strict control in both the later second trimester and the third trimester may be a reasonable strategy to reduce the risk of preeclampsia without increasing the risk of SGA.
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Objective:To explore the effects of interpregnancy interval (IPI) on pregnancy outcomes of subsequent pregnancy.Methods:A multicenter retrospective study was conducted in 21 hospitals in China. Information of age, height, pre-pregnancy weight, IPI, history of diseases, complications of pregnancy, gestational age of delivery, delivery mode, and pregnancy outcomes of the participants were collected by consulting medical records of pregnant women who had two consecutive deliveries in the same hospital during 2011 to 2018. The participants were divided into 4 groups according to IPI:<18 months, 18-23 months, 24-59 months and ≥60 months. According to the WHO′s recommendation, with the IPI of 24-59 months group as a reference, to the effects of IPI on pregnancy outcomes of subsequent pregnancy were analyzed. Stratified analysis was further carried out based on age, history of gestational diabetes mellitus (GDM), macrosomia, and premature delivery, to explore the differences in the effects of IPI on pregnancy outcomes among women with different characteristics.Results:A total of 8 026 women were included in this study. There were 423, 623, 5 512 and 1 468 participants in <18 months group, 18-23 months group, 24-59 months group and ≥60 months group, respectively. (1) The age, pre-pregnancy body mass index (BMI), history of cesarean section, GDM, gestational hypertension and cesarean section delivery rate of <18 months group, 18-23 months group, 24-59 months group and ≥60 months group were gradually increased, and the differences were statistically significant ( P<0.05). (2) After adjusting for potential confounding factors, compared with women in the IPI of 24-59 months group, the risk of premature delivery, premature rupture of membranes, and oligohydramnios were increased by 42% ( OR=1.42, 95% CI: 1.07-1.88, P=0.015), 46% ( OR=1.46, 95% CI: 1.13-1.88, P=0.004), and 64% ( OR=1.64, 95% CI: 1.13-2.38, P=0.009) respectively for women in the IPI≥60 months group. No effects of IPI on other pregnancy outcomes were found in this study ( P>0.05). (3) After stratified by age and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of oligohydramnios for women with advanced age ( OR=2.87, 95% CI: 1.41-5.83, P=0.004); and <18 months could increase the risk of premature rupture of membranes for women under the age of 35 ( OR=1.59, 95% CI: 1.04-2.43, P=0.032). Both the risk of premature rupture of membranes ( OR=1.58, 95% CI: 1.18-2.13, P=0.002) and premature delivery ( OR=1.52, 95% CI: 1.07-2.17, P=0.020) were significantly increased in the IPI≥60 months group. After stratified by history of GDM and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would lead to an increased risk of postpartum hemorrhage for women with a history of GDM ( OR=5.34, 95% CI: 1.45-19.70, P=0.012) and an increased risk of premature rupture of membranes for women without a history of GDM ( OR=1.44, 95% CI: 1.10-1.90, P=0.009). After stratified by history of macrosomia and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months could increase the proportion of cesarean section for women with a history of macrosomia ( OR=4.11, 95% CI: 1.18-14.27, P=0.026) and the risk of premature rupture of membranes for women without a history of macrosomia ( OR=1.46, 95% CI: 1.12-1.89, P=0.005). After stratified by history of premature delivery and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of premature rupture of membranes for women without a history of premature delivery ( OR=1.47, 95% CI: 1.13-1.92, P=0.004). Conclusions:Both IPI≥60 months and <18 months would increase the risk of adverse pregnancy outcomes in the subsequent pregnancy. Healthcare education and consultation should be conducted for women of reproductive age to maintain an appropriate IPI when they plan to pregnant again, to reduce the risk of adverse pregnancy outcomes in the subsequent pregnancy.
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Objective:To investigate the abnormal results of chromosomal microarray analysis (CMA) in the subsequent pregnancy of women with adverse pregnancy history, and explore the applicability of CMA in women with different genetic etiology.Methods:Out of 5 563 pregnant women who received CMA test in Nanjing Drum Tower Hospital during June 2014 and July 2020, 169 cases that underwent prenatal diagnosis due to isolated adverse pregnancy history were retrospectively collected in this study. All the participants were divided into three groups based on the etiology type of probands, genetic origin and expected CMA outcome: high-risk group ( n=19, including 11 cases with inherited pathogenic copy number variations and eight cases with inherited chromosomal abnormalities), low-risk group ( n=113, including six cases with negative whole exome sequencing and/or CMA findings, 31 cases with confirmed monogenic disease, 47 cases with de novo pathogenic copy number variations and 29 cases with de novo chromosomal abnormalities), and unknown risk group ( n=40, none of the cases underwent genetic testing). Descriptive statistical analysis was used to summarize the abnormal detection of each group. Results:There were 169 mothers with 172 fetuses finally enrolled, including two twins and one woman with two singleton pregnancies. A total of nine cases of abnormal fetuses were detected by CMA, accounting for 5.2% (9/172). Among them, eight were in the high-risk group, which were all caused by parental abnormalities, and one case in the low-risk group was detected with a de novo 22q11.22q11.23 microduplication, which was arr[GRCh37]22q11.22q11.23(22,997,928-25,002,659)×3. No abnormality was detected in the 40 patients of unknown risk group. Conclusions:Clarifying the etiology of isolated adverse pregnancy history is crucial to the rational application of CMA. Monogenic disease, unknown cause or negative finding of CMA in probands may not be an indication for prenatal diagnosis of CMA.
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BACKGROUND: Seroconversion of hepatitis B e antigen (HBeAg) is a critical event in the natural course of hepatitis B virus (HBV) infection. AIM: We herein characterize the virological factors associated with postpartum spontaneous HBeAg seroconversion. METHODS: A total of 214 pregnant women positive for both hepatitis B surface antigen (HBsAg) and HBeAg were followed up at 7-12 months postpartum. RESULTS: Of the subjects, 26 (12.1%) achieved spontaneous HBeAg seroconversion. Receiver operating curve analysis indicated that HBV DNA level <1.0â¯×â¯107â¯IU/mL, HBsAg <1.0â¯×â¯104â¯IU/mL and HBeAg <7.36â¯×â¯102 S/CO each independently predicted HBeAg seroconversion within 12 months postpartum. At delivery, 73.1% (19/26) women with postpartum HBeAg seroconversion had precore (PC) and/or basal core promoter (BCP) mutations, higher than that (5/36, 13.9%) in the women without postpartum seroconversion. Binary logistic regression analysis indicated that the presence of mutations in PC, BCP, and both PC and BCP at delivery was associated with an increased likelihood (ORâ¯=â¯13.286, 16. 238, and 22.143 respectively, all Pâ¯<â¯0.05) to undergo postpartum spontaneous HBeAg seroconversion. CONCLUSION: These results suggest that quantitative determination of virological markers and sequencing PC and BCP can predict spontaneous HBeAg seroconversion, which could be valuable in deciding antiviral therapy against HBV.
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Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis B Crónica/virología , Complicaciones Infecciosas del Embarazo/virología , Regiones Promotoras Genéticas , Adulto , Femenino , Hepatitis B Crónica/sangre , Humanos , Modelos Logísticos , Mutación , Periodo Posparto , Embarazo , Complicaciones Infecciosas del Embarazo/sangre , Prevalencia , Curva ROC , Seroconversión , Adulto JovenRESUMEN
Objective:To explore the relationship between fetal nuchal translucency (NT) in the first trimester and pregnancy outcome.Methods:A prospective cohort study was conducted in Nanjjing Drum Tower Hospital from December 2015 to December 2018, 4 958 singleton pregnant women were enrolled to screen fetal ultrasound structure and serology in the first trimester, ultrasound in the second trimester and neonatus physical examination 28 days after birth. According to the results of NT, 167 cases of fetus with increased NT (≥3.0 mm) and 4 791 cases of normal NT were divided, moreover, 86 cases with isolate increased NT and 81 cases of increased NT combined with structural abnormality. The prognosis of fetuses with different NT thickness was analyzed, and the pregnancy outcome of fetuses with isolate increased NT or combined with structural abnormality were analyzed. In the first trimester, if the fetal structure was abnormal or the serological screening result was high risk, the chromosomal microarray analysis (CMA) would be performed by chorionic villus sampling to determine the prenatal diagnosis.Results:(1) The pregnancy outcome for fetus of normal NT: there were 4 791 cases with normal NT. Totally, 4 726 cases with normal NT and no structural abnormalities were screened out in the firsttrimester. In this group, 5 cases of aneuploidies were diagnosed based on high risk of maternal serum biomarkers and 83 cases of structural abnormalities were screened out in the subsequent ultrasound scan and the neonatal examination. Another 65 cases with normal NT present complicated with structural anomalies were screened out in the first trimester and 4 cases were diagnosed as aneuploidies. (2) The pregnancy outcome for fetus of isolate increased NT: 66 (76.7%, 66/86) cases of isolated increased NT were performed CMA, 3 cases were diagnosed as trisomy 21 and terminated pregnancy. Another 4 cases were terminated pregnancy privately without cytogenetic diagnosis. No further anomalies were found in 79 cases till 6 to 21 months postnatally. (3) The pregnancy outcome for fetus of increased NT with structural anomalies: increased NT present with structural anomalies were screened out by detailed anomaly scan in the first trimester and 32 of them were confirmed as aneuploidies. In this group, 70 cases terminated pregnancy, 2 cases had spontaneous miscarriages and 9 cases had liveborns (1 newborn was found ventricular septal defect). (4) The pregnancy outcome for fetus of increased NT with or without structural anomalies: the percentage of aneuploidies in fetuses with isolated increased NT (3.5%, 3/86) was significantly lower than those with structural abnormalities (39.5%,32/81). The healthy survival rate in fetuses with isolated increased NT (91.9%,79/86) was significantly higher than those with structural abnormalities (9.9%, 8/81).Conclusions:A detailed first-trimester anomaly scan could improve prenatal screening efficiency of birth defects. Compared to the fetuses with increased NT combined with structural abnormalities, the healthy survival rate of fetuses with isolated increased NT based on detailed first-trimester anomaly scan is higher and the percentage of fetal aneuploidies is lower.
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Objective:To access the effectiveness and safety of the intrauterine balloon tamponade verse gauze packing combined with temporary abdominal aortic balloon occlusion in the management of placenta accreta spectrum (PAS).Methods:This was an open-label, randomized controlled trial conducted in Nanjing Drum Tower Hospital. The patients suspected with PAS for uterine preservation surgery under the multidisciplinary team care were recruited between Aug 2015 and Jan 2018. When bleeding could not be achieved after fetus delivered, and a temporary abdominal aortic balloon occlusion and the compression sutures as needed, the women were randomly allocated 1∶1 into balloon tamponade ( n=81) or gauze packing ( n=80) group. The primary outcome was successful bleeding arrests by avoiding second line surgeries. The secondary outcomes included the volume of blood loss during and after cesarean section, the rate of PPH, incidence and amount of blood transfusion, hysterectomy, postpartum pain, ICU admission, need for re-laparotomy, and the length of hospital stay, readmission, and interventional radiology complications. Results:All the women [100% (81/81)] in the balloon group were obtained hemostasis without further intervention, significantly higher than 88% (70/80) in the gauze group ( P=0.001). Before uterine tamponade, blood loss were 820 ml (620-1 230) ml and 850 ml (605-1 442) ml, while placenta bed were sutured in 96%（78/81, 77/80） respectively ( P>0.05).The proportion of blood loss≥1 000 ml was higher in the gauze group than that in the balloon group ( P=0.006). Maternal adverse events involving total blood loss, puerperal morbidity and postpartum pain occurred more frequently in the gauze group ( P<0.05). The following outcome showed no statistically significant difference between the two groups: the vascular occlusion time, the dose of radiation, and interventional radiology complication ( P>0.05). The median volume infused into the lower and upper balloons is 70 ml (50-100 ml) and 180 ml (100-240 ml). Conclusions:Incrauterine balloon tamponade is as effective as gauze packing in hemostasis following the placenta delivery in PAS. Compared with gauze packing, the uterine balloon tamponade is more effective.
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Objective:To investigate and analyze disease status and risk factors of venous thromboembolism (VTE) during pregnancy and puerperium in our country.Methods:Clinical datas were collected from 575 patients diagnosed with VTE during pregnancy and puerperium and hospitalized in nine medical institutions in our country from January 1, 2015 to November 30, 2019, and retrospectively analyzed it′s disease status and risk factors.Results:(1) The proportion of VTE in pregnancy and puerperium was 50.6% (291/575) and 49.4% (284/575), respectively. Four patients died, the mortality rate was 0.7% (4/575). The cause of death was pulmonary embolism. (2) The location of VTE during pregnancy and puerperium was mainly in the lower limb vascular (76.2%, 438/575), followed by pulmonary vessels (7.1%, 41/575). (3) In the risk factors of VTE, cesarean section accounted for 32.3% (186/575), maternal advance age accounted for 27.7% (159/575), braking or hospitalization during pregnancy accounted for 13.6% (78/575), other risk factors accounted for more than 5% were previous VTE, obesity, preterm birth, assistant reproductive technology conception and so on, pre-eclampsia and multiple pregnancy accounted for 4.9% (28/575) respectively. In addition, some patients with VTE did not have any of the above risk factors, and the incidence rate was as high as 23.1% (133/575).Conclusions:The occurrence of VTE during pregnancy and puerperium is related to multiple risk factors, and could lead to matemal death, It is very necessary to screen VTE risk factors for all pregnant women, to make corresponding prevention and control measures.
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Objective:To discuss the feasibility, safety and efficacy of kissing cover stents technique in the management of pseudoaneurysm near the bifurcation of innominate artery (the distance <1 cm).Methods:A retrospective study of 10 patients with pseudoaneurysm near the bifurcation of innominate artery were performed in the Affiliated Wuxi People’s Hospital of Nanjing Medical University from May 2013 to August 2018. There were 6 males and 4 females, aged from 25.0 to 77.0 years old, with a median age of 50.5 years old. All patients were treated with Viabahn stents combined with kissing stents. The adverse reactions were observed during the perioperative period, and the patients were followed up to evaluate the stents position and patency. Results:Among 10 patients, 2 were in the distal of innominate artery, 5 were in the bifurcation of innominate artery, 2 were in the root of right common carotid artery and 1 was in the origin of right subclavian artery. The distance from the injury site to the bifurcation of innominate artery was less than 5 mm in 4 cases and 8 mm in 1 case. All of them were successfully treated with Viabahn stents combined with kissing stents. Operation time ranged from 100.0 to 150.0 (122.0±14.9) min. The postoperative hospitalization time was (6.3±1.5) d, ranged from 4.0 to 9.0 d. During the operation, 8 mm×100 mm Viabahn stents were implanted in the right subclavian artery and 10 mm×100 mm Viabahn stents were implanted in the right common carotid artery. There were no severe adverse reactions during the perioperative period. Follow-up time ranged from 12 to 24 months. During the follow-up, color Doppler ultrasound and carotid CT angiography showed that the stents were in appropriate position, the blood flow was unobstructed, and there was no occlusion and displacement of stents. Viabahn stents remained at the level of proximal end of the innominate artery.Conclusion:Viabahn stents combined with kissing stents is a safe and effective treatment for pseudoaneurysm near the bifurcation of innominate artery.