Objective To analyze the causes of failed transcatheter closure for ventricular septal defects (VSD)in children. Methods One thousand two hundred and eighty children aged 13 to 141 months who underwent transcatheter closure from June 2009 to September 2013 in Guangdong General Hospital were selected. There were 43 failures(3. 36% ). The clinical data including transthoracic echocardiograph( TTE),radiography,interventional ap-proach and surgical findings were analyzed. Results Forty - three patients included 25 male and 18 female. The pa-tients' ages ranged from 13 to 141(43. 0 ± 31. 9)months and their weight ranged from 10 to 35(16. 3 ± 5. 59)kg. The causes of failure including doubly committed subarterial VSD misdiagnosed as perimembranous VSD(PMVSD)or intracristal VSD were in 6 patients. The size of occluder was too small in 13 cases,and there were statistical differences between three measurements of size of VSD(F = 19. 134,P = 0. 001). The size of VSD measured by left ventricular an-giography was significantly smaller than that measured by TTE,and there was statistical difference[(4. 78 ± 1. 11) mm vs(6. 48 ± 1. 43)mm,t = 4. 50,P = 0. 001]. The dimension of VSD measured by left ventricular angiography was significantly smaller than that measured by surgical findings,and there was statistical difference[(4. 78 ± 1. 11) mm vs(7. 02 ± 1. 08)mm,t = 5. 92,P = 0. 001]. But,the size of VSD measured by TTE had no significant difference compared with that measured by surgical findings(t = 1. 42,P = 0. 168). Aortic regurgitation occurred in 14 cases;atrioventricular block or left bundle branch block in 3 patients;tricuspid stenosis in 2 cases and residual shunt in 5 pa-tients. Conclusions Doubly committed subarterial VSD may be misdiagnosed as PMVSD or intracristal VSD. In the ca-ses of VSD concomitant with aortic valve prolapse,size of the occluders should be referred to VSD dimensions measured by TTE. In the cases of VSD adjacent to aortic valve,suitable occluders should be selected and operation technique should be improved to avoid aortic regurgitation.

Objective:To evaluate the objective imaging markers of cognitive impairment in patients with end-stage renal disease by MRI intravoxel incoherent motion.Methods:A total of 40 patients with ESRD were enrolled in the Department of Nephrology, Changzhou Second Hospital Affiliated to Nanjing Medical University from January 2019 to August 2020, and 24 healthy controls were prospectively enrolled at the same time.All subjects performed with MRI scan were collected, and the slow apparent diffusion coefficient (ADC slow) of the corresponding brain regions were obtained .The cognitive function was evaluated by the Montreal cognitive assessment scale (MoCA). Two-sample t test was used to analyze the difference of ADC slow and cognitive score between the two groups.Pearson correlation analysis was performed among the cognitive function score of end-stage renal disease and ADC slow value. Results:(1) The score of the intelligence test scale in the ESRD group (23.30±1.76) was significantly lower than that of the healthy control group (27.92±1.00) ( P<0.01). The ADC slow values of bilateral frontal lobe, hippocampus, and insula brain areas (respectively(0.648±0.035), (0.633±0.043), (0.762±0.043), (0.756±0.042), (0.792±0.048), (0.776±0.054))in the ESRD group were significantly higher than those in the healthy control group ((0.600±0.039), 0.610±0.037, (0.725±0.059), (0.711±0.054), (0.740±0.063), (0.716±0.051)) ( P<0.01). (2) Pearson correlation analysis showed that the ADC slow values of bilateral insula and right hippocampus in the ESRD group were negatively correlated with MoCA scales ( r=-0.38, -0.38, -0.66, all P<0.05). Conclusion:ADC slow value in IVIM can better reflect the changes of cognitive function impairment in ESRD patients.

Objective To evaluate the feasibility and diagnostic accuracy of CE-MRA with low dose contrast agent by comparison with DSA in diabetic patients with peripheral arterial diseases. Methods ( 1 )Study in vitro: test tubes containing Gd-DTPA of different concentrations were scanned, and the relationship between signal intensities and concentrations of GD-DTPA was analyzed. DSA and CE-MRA with selected concentrations of Gd-DTPA were performed on stenotic vascular models to estimate the proper low dose of GD-DTPA for clinical applications. (2) Clinical applications: 78 diabetic patients with peripheral arterial diseases were scanned from the abdomen and pelvis station to the calf-foot station in a 3 T MR system with standard bolus chase 3D CE-MRA sequence after injection of 13 ml GD-DTPA . The image quality,diagnostic rate of stenosis of arteries in calf and degree of venous contamination were evaluated with Fisher's exact test. DSA images of 220 vascular segments in 22 patients ( 10 segments per patient) were acquired as the gold standard and compared with CE-MRA by using Kappa test. Results The MR signal intensities were proportional to the concentrations of contrast agent in present study, and all stenotic segments of vascular model were displayed by CE-MRA with GD-DTPA at lower concentration of 1.5 mmol/L. As for MRA images of 78 diabetic patients with low dose Gd-DTPA, about 97.4% (76/78) showed diagnostic image quality for pelvic and thigh stations. But the MRA images of lower extremities were interfered by the venous contamination significantly (P ＜ 0.01 ). Compared with DSA for 22 patients, the diagnostic sensitivity, specificity and agreement coefficient (Kappa value) of MRA were 96. 0% ( 168/175), 73.3%(33/45), and 0.72 (P＜0.01), respectively. Conclusion Using 3.0 T MR scanner, high quality CE-MRA of lower limb arteries can be obtained for clinical applications with contrast agent dose as low as 13 ml,which has comparable diagnostic sensitivity and specificity with DSA. But the limitation of venous contamination in MRA image should be resolved in further studies.

OBJECTIVETo explore the genotype-phenotype correlation of a child with chromosome 18q deletion syndrome.

METHODSG-banded karyotyping, single nucleotide polymorphism array (SNP array) and fluorescence in situ hybridization (FISH) were performed on the child with abnormal phenotypes. Genotype-phenotype correlation was explored following accurate mapping of the breakpoints on chromosome 18q. SNP array was also performed on the genome DNA derived from peripheral venous blood samples from both parents.

RESULTSChromosomal analysis revealed that the child has a karyotype of 46, XY, del(18) (q23). SNP array analysis detected a 9.855 Mb deletion (chr18: 68 158 880-78 014 123) at 18q22.2q23. Mapping of the breakpoints suggested that the deletion has overlapped with that of distal chromosome 18q deletion syndrome and encompassed several critical regions for this syndrome. SNP array performed on parental samples suggested that the 18q22.2q23 deletion was de novo in origin. FISH analysis of peripheral blood sample from the child confirmed the presence of 18qter deletion.

CONCLUSIONThe phenotype of this child may be attributed to the deletion of distal 18q22.2q23, which has encompassed several critical regions for the 18q deletion syndrome.

Chromosome Deletion ; Chromosome Disorders ; genetics ; Chromosomes, Human, Pair 18 ; genetics ; Genetic Association Studies ; methods ; Genotype ; Humans ; Infant ; Phenotype ; Polymorphism, Single Nucleotide ; genetics

OBJECTIVE: To explore the mechanism of a false-negative result from karyotyping of chorionic villi cells for a trisomy 13 fetus featuring multiple malformations. METHODS: For a fetus with multiple malformations by ultrasonography and a 46,XY karyotype by chorionic villi analysis, amniocytes were further analyzed with quantitative fluorescence PCR (QF-PCR), G-banded karyotyping and chromosomal microarray analysis (CMA). Meanwhile, non-invasive prenatal testing (NIPT) was conducted on peripheral blood sample from the pregnant woman to determine the chromosomal composition of cytotrophoblast. After induction of labor, common aneuploidies in placenta and fetal tissue were also analyzed by QF-PCR. RESULTS: QF-PCR, chromosomal karyotyping and CMA analysis of the amniocytes all suggested complete trisomy 13 (47,XY,+13) in the fetus. NIPT also suggested existence of fetal trisomy 13. QF-PCR analysis of the placenta and fetal tissues revealed that cells derived from the maternal surface and right side of fetal surface harbored mosaic trisomy 13, while those derived from other sites of fetal surface of the placenta, umbilical cord, amniotic membrane and fetal muscle tissue harbored trisomy 13. CONCLUSION Karyotyping of long-term cultured chorionic villus sample may give rise to false negative results due to placental mosaicism. To ensure accurate prenatal diagnosis, discordance between karyotyping of chorionic villi cells, fetal ultrasound and NIPT result should be verified by amniocentesis or cordocentesis and application of multiple cytogenetic and molecular techniques.

OBJECTIVETo detect mutations of SLC25A13 gene in 20 families affected with citrin deficiency and provide prenatal diagnosis for them.

METHODSThe 20 probands and their parents were subjected to high-frequency mutation screening combined with Sanger sequencing. After confirming the genotype of each pedigree, genetic counseling and prenatal diagnosis were performed for their subsequent pregnancies.

RESULTSBiallelic pathogenic mutations of the SLC25A13 gene were identified in all probands. These included three deletions (c.851del4, c.1092_1095delT, and c.495delA), two splice-site mutations (IVS6+5G to A and IVS11+1G to A), two nonsense mutations (c.775C to T (p.Q259X) and c.72T to A (p.Y24X)), one duplication mutation (c.1638_1660dup), one insertion (IVSl6ins3kb), and one missense mutation (c.1775A to C (p.Q592P)). Among 24 fetuses undergoing prenatal diagnosis, 8 had normal genotypes, 11 were mutation carriers, while 5 harbored biallelic mutations. Those with wild type alleles or heterozygous SLC25A13 mutations were delivered. Two fetuses harboring homozygous c.851del4 mutations were also delivered. Three fetuses harboring biallelic mutations were terminated.

CONCLUSIONAnalysis of SLC25A13 gene mutations in families affected by citrin deficiency can provide evidence for molecular diagnosis and facilitate genetic counseling and prenatal diagnosis for the subsequent pregnancy, which can effectively reduce the risk of birth of further affected children.

Objective:To investigate the relationship between the changes of default network topology properties of brain function and cognitive function in patients with end-stage renal disease (ESRD).Methods:A total of 31 patients with ESRD were enrolled in the Department of Nephrology, Changzhou Second Hospital Affiliated to Nanjing Medical University from January 2019 to December 2020, and 18 healthy persons were included in the same period as the control group.The cognitive function was evaluated with the Montreal cognitive assessment (MoCA) and trail making tests, and then the subjects were examined by resting-state functional magnetic resonance imaging (rs-fMRI). After preprocessing, the brain functional network was constructed and the topology properities of the network were calculated.The SPSS 20.0 software was used for statistical analysis.Independent sample t-test, chi square test and Pearson correlation analysis were used for data statistics. Results:(1) The score of MoCA in the ESRD group(23.37±1.77) was significantly lower than that in the healthy control group(27.94±1.13)( t=9.537, P<0.001). (2) The levels of Eglobal, Elocal, Cp and Sigma in ESRD group ((0.129±0.025), (0.148±0.040), (0.188±0.046), (1.593±0.650)) were significantly lower than those in healthy control group ((0.160±0.040), (0.212±0.024), (0.276±0.049), (2.004±0.864))( t=3.591, 7.474, 7.058, 2.034, all P<0.05). The Lp value of the ESRD group (8.131±1.905) was significantly higher than that of the control group (6.777±2.150)( t=2.583, P< 0.05). The node efficiency values of bilateral dorsolateral superior frontal gyrus, left middle frontal gyrus, bilateral posterior cingulate gyrus, right hippocampus, left superior marginal gyrus, bilateral angular gyrus and bilateral cuneate anterior lobe in ESRD group ((0.133±0.071), (0.201±0.047), (0.211±0.106), (0.175±0.066), (0.276±0.113), (0.122±0.146), (0.042±0.075), (0.171±0.027), (0.154±0.078), (0.240±0.095), (0.161±0.056))were lower than those in the healthy control group((0.312±0.075), (0.289±0.091), (0.277±0.132), (0.284±0.053), (0.368±0.063), (0.231±0.227), (0.120±0.162), (0.296±0.064), (0.310±0.186), (0.318±0.066), (0.286±0.103))( t=2.107-9.436, all P<0.05). (3)Pearson correlation analysis showed that the node efficiency values of bilateral posterior cingulate gyrus and right hippocampus in ESRD group were positively correlated with the score of MoCA( r=0.36, 0.49, 0.53, all P<0.05). Conclusion:The topological structure of brain functional network is abnormal in ESRD patients, which can affect the cognitive function of patients.

Objective To investigate the role of nitric oxide synthase(NOS)in the regulation of myocardial ischemia-reperfusion(IR)injury in ovariectomized(OVX)rats.Methods A total of 132 female SD rats were subjected,and 48 of them were randomly divided into sham operation group,IR group,OVX group and combined group,with 12 in each group.In order to explore the role of endothelous NOS(eNOS)and inducible NOS(iNOS)in ovariectomization increasing myo-cardial IR injury,another 84 mice were divided into negative sham group,negative IR group,nega-tive combined group,eNOS+IR group,eNOS combined group,iNOS small interfering RNA(si-iNOS)+IR group and si-iNOS combined group,with 12 in each group.The mice of the corre-sponding groups were injected with adeno-associated virus(AAV)overexpressing eNOS or knoc-king down iNOS via tail vein before OVX modeling.Myocardial infarct size,serum levels of lac-tate dehydrogenase(LDH)and creatine phosphokinase isoenzyme(CK-MB),LVEF,LVFS,and expression levels of eNOS and iNOS in the myocardial tissues were measured.Results The com-bined group had significantly increased level of iNOS in myocardium,larger myocardial infarct size and elevated serum LDH and CK-MB levels,but decreased myocardial expression of eNOS and LVEF and LVFS values than the IR group(P＜0.05).When compared with the negative combined group,the myocardial infarct size and serum LDH and CK-MB levels were decreased[(23.51±3.22)％and(26.21±2.93)％vs(58.78±5.42)％,(176.31±15.48 and 169.52±17.12 vs 328.85±37.12 U/L,35.41±6.41 and 34.77±5.94 vs 88.73±9.14 U/L,P＜0.05],and the LVEF and LVFS values were increased[(41.31±3.12)％and(42.09±3.41)％vs(30.77± 2.15)％,(21.47±1.57)％and(21.32±1.42)％vs(15.92±1.33)％,P＜0.05]in the eNOS com-bined group and si-iNOS combined group.Conclusion The decrease of eNOS expression and in-crease of iNOS expression are related to the aggravation of myocardial IR injury in OVX rats.

Objective:To investigate the short-term and long-term efficacy of laparoscopic surgery for colorectal cancer in elderly patients aged 80 and over.Methods:This study included patients aged 80 and over with sigmoid or rectal cancer who had undergone radical surgery in Beijing Hospital between January 2013 and December 2020.Of the enrolled patients, 47 underwent laparoscopic surgery, and 44 received open surgery.After 1∶1 propensity score matching(PSM), there were 32 cases in each group.Patient clinicopathological characteristics, surgery data, post-operative outcomes and long-term survival were compared.Results:Before PSM, there were significant differences in sex composition and tumor locations between the open surgery and laparoscopic surgery groups.After PSM, there was no significant difference in clinicopathological characteristics between the two groups.Before and after PSM, the operative time for laparoscopic surgery was statistically longer than that for open surgery.The intraoperative blood loss, the postoperative complication rate and the number of harvested lymph nodes were not significantly different between the two groups before and after PSM.Before and after PSM, the postoperative hospital stay in the laparoscopic operation group was shorter than that in the open surgery group, but the difference was not statistically significant.Before PSM, the 1-year, 3-year and 5-year survival rates of the open surgery group were 92.4%, 69.5% and 58.1%, respectively, and the 1-year, 3-year and 5-year survival rates of laparoscopic group were 91.3%, 79.8% and 69.5%, respectively.There was no significant difference in overall survival between the two groups before PSM( χ2=0.591, P=0.422). After PSM, the 1-year, 3-year and 5-year survival rates in the open surgery group were 89.3%, 67.1% and 52.2%, respectively, and the 1-year, 3-year and 5-year survival rates in the laparoscopic surgery group were 90.6%, 74.3% and 65.0%, respectively.There was no significant difference in the overall survival between the two groups after PSM( χ2=1.316, P=0.251). Conclusions:For elderly colorectal cancer patients aged 80 and over, laparoscopic surgery and open surgery have similar rates of complications and long-term survival.This study provides evidence for the safety of laparoscopic surgery.Further prospective randomized controlled clinical trials are needed to confirm these findings.

Objective To investigate the effect of ERH gene knockdown on the proliferation and apoptosis of human bladder cancer T24 cells. Methods T24 cells infected by lentivirus with interference on ERH gene sequence were cloned to establish stable T24 cells clone in ERH gene suppression. The expression of ERH mRNA gene in bladder cancer was detected by using quantitative real time polymerase chain reaction (qPCR). The effects of ERH knockout on the cell proliferation and apoptosis were examined by using methylthiazolyl tetrazolium (MTT) assay, colony formation assay and flow cytometry. The effect of ERH knockout on the tumorigenic effect of T24 cells in vivo was verified by subcutaneous tumor formation in nude mice. Results After lentiviral transfection, qPCR results showed that the knockdown effect of ERH mRNA in ERH normal group (untreated T24 cells) was better than that in ERH gene knockdown group, and the difference was statistically significant [(1.006±0.126) vs. (0.079±0.007); t=12.72, P=0.0002]. After knocking out ERH gene, MTT assay showed that the proliferation ability of T24 cells in ERH gene knockdown group was weakened compared with ERH normal group, and the difference was statistically significant [A490 value: (0.13±0.00) vs. (0.66±0.01);t=104.61, P<0.0001]. Colony formation assay indicated that the ability of clone in ERH normal group was weakened compared with ERH gene knockdown group [(10.5 ±1.2) vs. (196.4 ±4.0); t= 73.63, P< 0.0001]. Flow cytometry showed that the cell apoptosis rate in ERH gene knockdown group was higher than that in ERH normal group [(11.0 ±0.5) ％ vs. (4.2 ±0.5) ％; t= 16.06, P<0.0001]. Imaging results of subcutaneous tumor formation in nude mice showed that the total fluorescence intensity of the tumor area in ERH gene knockdown group was (4.67 ±0.59) × 1010 μW/cm2, and the corresponding part in ERH normal group was (9.54±4.20) × 1010μW/cm2 (t=3.64, P=0.0051);tumor weight in ERH gene knockdown group was (0.80±0.62) g, and in ERH normal group was (1.79±0.71) g (t=3.33, P=0.0037). Conclusion ERH gene knockout can inhibit the proliferation of human bladder cancer T24 cells, and promote the cell apoptosis.