OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the detection of fetal anomalies among pregnant women with advanced age. METHODS: CMA results of 562 cases, in addition with the outcome of pregnancy and neonatal follow-up were reviewed. RESULTS: Among the 562 amniotic fluid samples, 73 cases (12.99%) of fetal chromosomal abnormalities were detected, which included 21 cases (3.73%) of chromosomal aneuploidies and 52 cases (9.25%) of copy number variations (CNVs). The latters included 27 cases of pathological CNVs (4.80%), 4 cases of possible pathogenic CNVs (0.71%) and 42 cases of variants with unknown clinical significance (7.47%). Compared with those under 35, the detection rate of fetal chromosomal aneuploidies for women with advanced age was higher under the indications of voluntary test, abnormal ultrasonic structures, abnormal ultrasonic soft index and risks indicated by non-invasive prenatal testing (NIPT). No significant difference was found in the detection rate of CNVs between those ≥35 and <35 and between those with age factor only and with additional indications (P> 0.05). 552 cases (98.22%) of pregnant women have completed the followed up. Among 31 women with pathological and possible pathogenic fetal CNVs detected by CMA, 25 had terminated the pregnancy, 6 (19.35%) have delivered without obvious abnormality. 41 pregnant women with fetal CNVs of unknown clinical significance have completed the follow up, among whom 3 had terminated the pregnancy, 1 newborn was found with malformation after birth, which yielded an abnormal pregnancy rate of 9.76%. 480 pregnant women with negative CMA results have completed the follow up, among whom 5 (1.04%) had abnormal pregnancy or delivered a child with birth defect. CONCLUSION There is a certain difference between the outcome of pregnancy predicted by CMA testing and the actual outcome. The pregnancies with fetal CNVs with unknown clinical significance detected by CMA have a high adverse rate, which should attract clinical attention. CMA testing should be recommended for pregnant women with advanced age regardless of whether they have other symptoms. CMA combined with other detection methods is the trend for prenatal diagnosis.
Aneuploidy ; Chromosome Aberrations ; DNA Copy Number Variations ; Female ; Humans ; Infant, Newborn ; Maternal Age ; Oligonucleotide Array Sequence Analysis ; Pregnancy ; Prenatal Diagnosis

AIM: To explore the effect of single nucleotide polymorphism (SNP) of breast cancer susceptibility gene 1 (BRCA1) on chemotherapy sensitivity and survival prognosis of patients with metastatic esophageal squamous cell carcinoma. METHODS: A total of 153 patients with newly treated metastatic esophageal squamous cell carcinoma who were admitted to Suzhou Science and Technology City Hospital from June 2016 to February 2020 were included and administered with cisplatin combined with capecitabine chemotherapy. Before the first chemotherapy, 5 mL of venous blood was collected to extract DNA, and the TaqMan probe method was used to detect the genotypes of the BRCA1 gene rs8176318G/T, rs799917T/C and rs1799966T/C polymorphic loci. The objective response rate (ORR) and overall survival (OS) of different genotypes were analyzed. RESULTS: Rs799917T/C polymorphism was closely related to the chemosensitivity of metastatic esophageal squamous cell carcinoma. The chemotherapy response rates of TT, TC and CC genotypes increased gradually (TT 22.5%, TC 38.6%, CC 55.3%, χ

Biochemistry experiment is an experimental module associated with biochemistry curriculum. In the context of deepening the education reform on innovation & entrepreneurship, integrating the concept of innovation & entrepreneurship with the experimental course is an effective way for the biology discipline to foster professional talents with strong engineering ability and innovation & entrepreneurship ability. Outcome-based education (OBE) is a new concept for education. Guided by this concept, we encouraged students to propose and take part in research projects, redesigned the time frame for research project-based experiment teaching, and implemented a multi-dimensional evaluation system along the entire teaching process. Furthermore, we integrated the concept of innovation & entrepreneurship for training undergraduates during the teaching process of biochemistry experiment. These measures not only boosted the students' interest in research and innovation, but also guided the teachers to participate in the entire process, which helped improving the engineering ability and innovation & entrepreneurship ability of the students.
Biochemistry/education* ; Curriculum ; Entrepreneurship ; Humans ; Students

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.

Radiation-induced bystander effect (RIBE) refers to that irradiated cells release signaling factors and induce responses in nonirradiated cells.In other words, it is the communication between irradiated and nonirradiated cells by intracellular signals. RIBE could influence the efficacy of tumor radiotherapy, but also has potential risk to the normal tissues outside of radiation field. Studies have found that ionizing radiation can induce the alteration of miRNA expression not only in the irradiated cells but also in adjacent nonirradiated tissues, and miRNAs may play an important role in the regulation of signaling pathways between irradiated and nonirradiated bystander cells. This article reviewed the roles of miRNAs in RIBE.

The clinical characteristics and gene mutation characteristics of a child with typical maple syrup urine disease were analyzed retrospectively.The child is a boy, who showed unexplained milk refusal, poor reaction, foaming at the mouth, and encephalopathy symptoms 7 days after birth.The total leucine concentration was abnormally increased by blood tandem mass spectrometry, and the results of urine gas chromatography/mass spectrometry suggested that the concentrations of 2-hydroxy isovaleric acid, 2-keto isovaleric acid, 2-keto-3-methylpentanoic acid and 2-keto-isohexanoic acid were significantly increased.The gene detection results showed that c. 1028delC (p.S343Lfs*9) homozygous mutation was found in the BCKDHB gene.Understanding the clinical symptoms and gene mutation characteristics of this disease can help with the early detection and early diagnosis of this disease, so as to improve its prognosis to the greatest extent.

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.

Objective: To investigate the risk factors for drug resistance of urinary tract infections-causing Escherichia coli producing extended spectrum beta-Lactamases (ESBLs) in elderly people (≥65 years old), in order to provide evidence for rational use of antibiotics in clinic. Methods: Clinical data of elderly patients diagnosed as urinary tract infections in Beijing Chao-Yang Hospital from January 2016 to December 2017 were retrospectively analyzed. According to whether ESBLs were produced by Escherichia coli isolated from urine samples, the patients were divided into the ESBLs-producing E. Coli group (ESBLs group) and the control group. Single factor analysis was performed by Chi-square test.Logistic regression analysis was used to analyze the risk factors for ESBLs-producing Escherichia coli infections in urinary tract on the basis of statistical significance. Results: A total of 452 strains of Escherichia coli were isolated, including 253 strains (55.97%) producing ESBLs, and 199 strains (44.03%) not producing ESBLs. The ureteral calculi (OR=2.675, 95%CI: 1.129-6.341), urinary obstructive diseases (≥ 2 kinds) (OR=8.680, 95%CI: 2.508-30.040), indwelling catheters (OR=5.762, 95%CI: 2.698-12.155), antibiotic treatment more than 2 weeks for urinary tract infections within one year (OR=3.461, 95%CI: 1.766-6.784) were independent risk factors for ESBLs-producing Escherichia coli urinary tract infections. The incidence rate of Escherichia coli resistance to various antibiotics was higher in elderly patients with urinary tract infection than in non-elderly patients. Conclusions Escherichia coli producing ESBLs can be easily isolated from elderly patients with urinary tract obstructive diseases, indwelling catheters and repeated long-term administration of broad-spectrum antibiotics. The proportion of ESBLs Escherichia coli-caused urinary tract infections is higher in elderly patients. Thereby, carbapenems or piperacillin/tazobactam is the reasonable antibiotics. Ampicillin, piperacillin, levofloxacin and ciprofloxacin should not be the first choice for the treatment of urinary tract infections in the elderly.

Objective To evaluate the risk factors and sonographic findings of pregnancies complicated by placenta increta or placenta percreta. Methods Totally, 2219 cases were retrospectively analyzed from 20 tertiary hospitals in China from January 2011 to December 2015. The data were collected based on the original case records. All cases were divided into two groups, the placenta increta (PI) group (79.1％, 1755/2219) and the placenta percreta (PP) group (20.9％, 464/2219), according to the degree of placental implantation. The risk factors and sonographic findings of placenta increta or percreta were analyzed by uni-factor and logistic regression statistic methods. Results The risk factors associated with the degree of placental implantation were age, gravida, previous abortion or miscarriage, previous cesarean sections, and placenta previa (all P<0.05), especially, previous cesarean sections (χ2=157.961) and placenta previa (χ2=91.759). Sonographic findings could be used to predict the degree of placental invasion especially the boundaries between placenta and uterine serosa, the boundary between placenta and myometrium, the disruption of the placental-uterine wall interface and loss of the normal retroplacental hypoechoic zone(all P<0.01). Conclusions Previous cesarean sections and placenta previa are the main independent risk factors associated with the degree of placenta implantation. Ultrasound could be used to make a prenatal suggestive diagnosis of placenta accreta spectrum disorders.

Objective To assess the current practice in managing hypertensive disorders of pregnancy (HDP) and provide possible interventions to improve the quality of care.MethodsA checklist was developed based on Chinese Medical Association's guideline on HDP. A criteria-based audit was conducted on 66 HDP patients who were admitted to the Intensive Care Unit (ICU) of Nanjing Drum Tower Hospital,The Affiliated Hospital of Nanjing University Medical School between January 1, 2014 and December 31, 2016. The quality of care during antepartum and hospitalized period were evaluated, and patient factors were also considered. We also collected data on patients' demographics, complications of HDP, acute physiology and chronic health evaluation (APACHE)Ⅱ score and duration of hospital stay.T or Mann-WhitneyU test orChi-square test was performed. Results(1) From 2014 to 2016, the number of deliveries in Nanjing Drum Tower Hospital was 18573, with 1561 cases (8.4％) of HDP. Among the 66 cases being audited, 44 (66.7％) were preeclampsia; 16 (24.2％) were preeclampsia complicated by chronic hypertension; six (9.1％) were eclampsia; no maternal death was reported. (2) Complications of HDP in this study included heart failure (17 cases, 25.8％), hemolysis, elevated liver enzyme levels, low platelet count (HELLP) syndrome (15 cases, 22.7％), anemia and/or thrombopenia requiring transfusion (12 cases, 18.2％), renal dysfunction (seven cases, 10.6％), eclampsia (six cases, 9.1％), pulmonary edema/acute respiratory distress syndrome (five cases, 7.6％), placenta abruption (four cases, 6.1％), cerebral venous and sinus thrombosis (two cases, 3.0％), cerebral hemorrhage (one case, 1.5％) and hepatic rupture (one case, 1.5％). Their APACHEⅡ score was 9.0±3.9. The duration of ICU and hospital stay was 2 (1-30) d and 8 (4-32) d, respectively. (3) Compared with the gravidas who registered during antenatal care, those without registrations were older [(33.0±6.0) vs (29.1±5.4) years old,t=-2.616], having less antenatal visits [2 (0-4) vs 5 (2-10) times, Z=110.000] and higher blood pressure on admission [(177.0±24.1) vs (155.5±24.6) mmHg of systolic blood pressure (t=-3.322), and (116.4±14.6) vs (108.0±18.7) mmHg of diastolic blood pressure (t=-3.013, 1 mmHg=0.133 kPa)], and only a few of them were nulliparas [23.8％(5/21) vs 71.1％(32/45),χ2=13.006] (all P<0.05). (4) Among the 66 cases, seven (10.6％) had preeclampsia history, but none of them received aspirin for HDP prevention; 21 (31.8％) did not have regular testing of blood pressure during antenatal check; 24 (36.4％) did not receive proper antenatal evaluation when hypertension was identified. (5) After excluding 20 cases directly admitted upon the first diagnosis of HDP, the rest 46 were managed in the outpatient department. Eighteen of them (39.1％) did not have blood pressure monitoring and 26 of them (56.5％) did not have a regular test of hemoglobin, platelet, urine protein, liver or renal function. (6) Twenty-nine gravidas (43.9％) suffered a delay in referral or admission. (7) All gravidas received magnesium sulphate administration. Thirty-three cases with severe hypertension (systolic blood pressure≥160 mmHg or diastolic blood pressure≥110 mmHg) were given antihypertensive drugs with satisfactory blood pressure control. Thirty-six cases with living fetus (26-34+6 gestational weeks) received antenatal dexamethasone. Termination of pregnancy was delayed in three cases after admission.ConclusionsThe management of HDP is not good enough in patients' education, screening for high-risk population, early diagnosis and antenatal care. Quality improvement efforts should be focused on strengthening patient education, training of doctors in primary and secondary hospitals, implementing protocols on antepartum care of preeclampsia and establishing a referral system for patients with severe obstetric complications.