Objective:To explore the genetic etiology of fetuses with congenital heart disease (CHD) through whole exome sequencing (WES).Methods:Thirty seven fetuses identified with CHD by prenatal ultrasonography but with negative results by chromosomal microarray analysis (CMA) at Jinhua Maternal and Child Health Care Hospital from January 2020 to June 2022 were selected as the study subjects, for whom WES was carried out.Results:WES and Sanger sequencing had detected 6 pathogenic or likely pathogenic variants, and 6 variants with unknown clinical significance. The variants had involved 15 loci within 11 genes, in addition with one copy number variation.Conclusion:WES can increase the detection rate for genetic abnormalities among fetuses with CHD, which can facilitate the prenatal diagnosis, evaluation of prognosis and genetic counseling for the couples.

Objective:To explore the expression of homologous recombination repair (HRR) deficiency related genes in endometrial cancer and their relationship with clinical pathological features and immune infiltration.Methods:A total of 53 patients with endometrial cancer (endometrial cancer group) who underwent surgical treatment at the Affiliated People′s Hospital of Shandong First Medical University from June 2018 to June 2020 were selected as the study subjects. Clinical data of the patients were retrospectively analyzed, and 50 healthy women who underwent physical examinations were selected as the control group. Clinical and pathological characteristics of 53 patients with endometrial cancer were collected, and real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was performed Methods The mRNA expressions of human breast cancer susceptibility gene 1 (BRCA1), tumor suppressor gene homologous loss phosphatase tensin gene (PTEN) on chromosome 10 in the peripheral blood of the subjects were detected, and the proportions of CD 4+ T cell subsets in peripheral blood monocytes were detected by flow cytometry; Pearson analysis of the correlation between peripheral blood BRCA1, PTEN mRNA expression and various subsets of CD 4+ T cell; Analysis of prognostic factors for endometrial cancer using COX risk regression model. Results:The peripheral blood BRCA1 and PTEN mRNA expression levels in patients with endometrial cancer were higher than those in the healthy control group: 2.87 ± 0.65 vs. 1.02 ± 0.13, 3.25 ± 0.74 vs. 1.01 ± 0.20, and the differences were statistically significant ( P<0.01). The proportion of peripheral blood helper T cell-2 (Th2), helper T cell-17 (Th17), regulatory T cell (Treg) and helper T cell-22 (Th22) in patients with endometrial cancer was significantly higher than that in the healthy control group: (10.72 ± 1.33)% vs. (5.43 ± 0.80)%, (9.78 ± 0.80)% vs. (3.31 ± 0.62)%, (10.81 ± 1.29)% vs. (5.74 ± 0.69)%, (6.09 ± 0.70)% vs. (3.09 ± 0.73)%, and the proportion of helper T cell-1 (Th1) was significantly lower than that in the healthy control group: (5.54 ± 0.90)% vs. (13.07 ± 2.55)%, the difference was statistically significant ( P<0.01). The peripheral blood BRCA1 and PTEN mRNA expression levels were significantly higher in patients with muscle infiltration depth ≥1/2, histological grade G 2 to G 3, lymph node metastasis, and International Federation of Obstetrics and Gynecology (FIGO) stage Ⅲ to Ⅳ than in patients with muscle infiltration depth<1/2, histological grade G 1, no lymph node metastasis, and FIGO stage Ⅰ to Ⅱ, with statistical significance ( P<0.01 or<0.05). Peripheral blood BRCA1 and PTEN mRNA were significantly positively correlated with Th2, Th17, Treg and Th22 ratios ( P<0.01), and negatively correlated with Th1 ratios ( P<0.01). COX risk regression analysis showed that histological grading, FIGO staging, depth of muscle infiltration, peripheral blood BRCA1 and PTEN mRNA expression with lymph node metastasis were all independent prognostic factors for endometrial cancer ( P<0.01 or<0.05). Conclusions:HRR deficiency related genes BRCA1 and PTEN mRNA exhibit high levels in patients with endometrial cancer, and are closely related to muscle infiltration depth, histological grading, lymph node metastasis, and FIGO staging. They can also affect the immune microenvironment of endometrial cancer patients, thereby affecting disease progression and prognosis.

Objective:To evaluate the effects of split-filter dual-energy CT (SF-DECT) in improving image quality at low doses in the process of abdominal examinations for children.Methods:A preliminary study was conducted using child phantoms. Furthermore, 20 children aged 4-6 years were recruited prospectively for clinical validation from June 2020 to December 2020. Conventional single-energy CT (SECT) and SF-DECT were employed to scan the abdominal areas of the phantoms and children. Then, the CT values, image noise, contrast to noise ratios (CNRs), and image subjective scores of SF-DECT and SECT were compared under various doses (1, 2, 3, and 4 mGy).Results:For the phantoms under doses of 3 and 4 mGy, SF-DECT decreased the image noise by 18.9% and 23.6%, respectively, and increased the liver and kidney CNRs (CNR liv and CNR kid) by 12.8% and 31.9% at most, respectively, compared to SECT ( Z = 3.00, 5.17, P < 0.001). For children, SF-DECT decreased image noise ( Z = 4.64, P < 0.001) and increased CNR liv and CNR kid ( Z = 3.78, 3.39, P < 0.001). For both the phantoms and the children, the subjective scores of images scanned using the SF-DECT were higher than those scanned using the SECT ( Z = 1.96-3.80, P < 0.05). Conclusions:Compared with SECT, SF-DECT can improve the quality of children′s abdominal images. This technique has a certain prospect of optimizing abdominal CT for children. However, it is necessary to conduct in-depth clinical research to verify the result.

Objective:To investigate the changes of T1 and T2 values in residual liver after major liver resection in rats and the relationship with pathologic indices related to liver regeneration.Methods:Seventy healthy male Sprague Dawley rats, SPF grade, aged 7-8 weeks, weighting 250-280 g, were divided into MR scan group ( n=14) and pathologic analysis group ( n=56). The MR scan group was further divided into partial hepatectomy group ( n=7) and the sham operation group ( n=7). MRI T 1 mapping and T 2 mapping were performed before surgery and on day 1, 2, 3, 5, 7, 14, 21 after surgery. T1 and T2 values of liver parenchyma were measured. In the pathologic analysis group, 7 rats were randomly included at each time point before and after surgery for pathologic examination, the diameter and proliferative activity (Ki-67 indices) of hepatocytes were assessed. The changes of imaging and pathologic indices were observed, and the correlations between MR parameters and liver volume and pathologic indices were analyzed. Results:Both T1 and T2 values in liver parenchyma were increased on day 1 after surgery and reached their maximum values on day 2 ( P=0.005 and P<0.001, compared with baseline), then were gradually decreased, and recovered to the preoperative level on day 14 and 21 ( P>0.05), respectively. T2 value was correlated with hepatocyte diameter, liver volume and Ki-67 indices better ( r=0.640, -0.764, 0.765, respectively, all P<0.001). T1 value was correlated with hepatocyte diameter, liver volume and Ki-67 indices ( r=0.472, -0.481 and 0.444, all P<0.001). Conclusion:The T1 and T2 values of rats liver remnant parenchyma showed regular changes, and were correlated with liver regeneration indices, which reflect the microscopic changes of rat liver remnant parenchyma, and are expected to be used for quantitative monitoring of liver remnant regeneration.

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for fetuses with choroid plexus cysts (CPC) detected by prenatal ultrasonography. METHODS: Amniotic fluid chromosomal karyotype was analyzed in 104 fetuses with CPC, and copy number variations (CNVs) among the fetuses were detected by using CMA. RESULTS: Ten fetuses (9.62%) were found to have an abnormal karyotype, and 14 additional CNVs were detected in those with a normal karyotype. The fetuses were divided into isolated CPC group (n = 87) and non-isolated CPC group (n = 17) based on the presence of additional ultrasonographic abnormalities. The detection rates for karyotypic abnormalities of the two groups were 4.6% and 35.3%, respectively, whilst those for the CMA were 4.6% and 47.1%, respectively. The detection rates for karyotypic abnormalities and CMA of the non-isolated CPC group were significantly higher than those of the isolated CPC group (P < 0.05). The detection rate for CMA in the non-isolated group was significantly higher than chromosomal karyotype abnormalities (P < 0.05). Among the 8 fetuses with abnormal CMA, 4 had single umbilical artery, 3 had abnormal cardiac structure, and 2 had enhanced intestinal echo. CONCLUSION CPC is closely associated with chromosomal abnormalities. Chromosome karyotype analysis in combination with CMA can effectively detect fetal chromosomal abnormalities and provide a basis for genetic counseling.
Humans ; Female ; Pregnancy ; DNA Copy Number Variations ; Choroid Plexus/diagnostic imaging* ; Microarray Analysis ; Karyotype ; Chromosome Aberrations ; Amniotic Fluid ; Cysts

Objective:To establish a clinical diagnostic scoring model for preoperative predicting hepatocellular carcinoma (HCC) microvascular invasion (MVI) based on gadolinium-ethoxybenzyl-diethylenetriamine pentacetic acid (Gd-EOB-DTPA) enhanced MRI, and verify its effectiveness.Methods:From January 2014 to December 2020, a total of 251 cases with pathologically confirmed HCC from Tianjin First Central Hospital and Jilin University First Hospital were retrospectively collected to serve as the training set, while 57 HCC patients from Tianjin Medical University Cancer Hospital were recruited as an independent external validation set. The HCC patients were divided into MVI positive and MVI negative groups according to the pathological results. The tumor maximum diameters and apparent diffusion coefficient (ADC) values were measured. On the Gd-EOB-DTPA MRI images, tumor morphology, peritumoral enhancement, peritumoral low intensity (PTLI), capsule, intratumoral artery, intratumoral fat, intratumoral hemorrhage, and intratumoral necrosis were observed. Univariate analysis was performed using the χ 2 test or the independent sample t-test. The independent risk factors associated with MVI were obtained in the training set using a multivariate logistic analysis. Points were assigned to each factor according to the weight value to establish a preoperative score model for predicting MVI. The receiver operating characteristic (ROC) curve was used to determine the score threshold and to verify the efficacy of this scoring model in predicting MVI in the independent external validation set. Results:The training set obtained 98 patients in the MVI positive group and 153 patients in the MVI negative group, while the external validation set obtained 16 patients in the MVI positive group and 41 patients in the MVI negative group. According to logistic analysis, tumor maximum diameter>3.66 cm (OR 3.654, 95%CI 1.902-7.018), hepatobiliary PTLI (OR 9.235, 95%CI 4.833-16.896) and incomplete capsule (OR 6.266, 95%CI 1.993-9.345) were independent risk factors for MVI in HCC, which were assigned scores of 3, 4 and 2, respectively. The total score ranged from 0 to 9. In the external validation set, ROC curve analysis showed that the area under the curve of the scoring model was 0.918 (95%CI 0.815-0.974, P=0.001). When the score>4 was used as the threshold, the accuracy, sensitivity, and specificity of the model in predicting MVI were 84.2%, 81.3%, and 85.4%, respectively. Conclusions:A scoring model based on Gd-EOB-DTPA-enhanced MRI provided a convenient and reliable way to predict MVI preoperatively.

Objective: To investigate the changes of plasma protein expression profile in hyperhomocysteinemia rats and the protective effect of highly expressed angiopoietin 1 in plasma on endothelial cells. Methods: The hyperhomocysteinemia animal model was established. The difference in plasma protein content was analyzed by label-free protein spectroscopy. The effects of homocysteine and angiopoietin 1 on endothelial cell migration and proliferation were detected by wound healing and CCK-8 proliferation assay. Results: The results of protein profiling showed that 5 proteins were significantly up-regulated and 17 proteins were significantly down-regulated in the plasma of hyperhomocysteinemia rats, among which angiopoietin 1 was significantly up-regulated. In endothelial cells in the superior mesenteric artery of rats, treatment with 30 or 50 μmol/L homocysteine for 24 h significantly inhibited the migration and proliferation. Angiopoietin 1(600 ng/ml) significantly reduced the migration and proliferation of endothelial cells inhibited by 30 μmol/L homocysteine, but had no significant effect on the migration and proliferation of endothelial cells inhibited by 50 μmol/L homocysteine. Conclusion Hyperhomocysteinemia can significantly affect the protein expression profile in plasma. Angiopoietin 1 in plasma can compensate for the damage of vascular endothelial migration and proliferation function caused by homocysteine in a certain concentration range.

OBJECTIVE: To explore the value of non-invasive prenatal testing (NIPT) for the detection of fetal chromosome copy number variations (CNVs). METHODS: Clinical data of 18 661 pregnant women who underwent NIPT were collected. For fetuses suspected for carrying CNVs, amniotic fluid samples were collected for chromosomal karyotyping and/or chromosomal microarray analysis (CMA). RESULTS: Among all samples, NIPT suggested that 58 fetuses carried trisomy 21, 18 carried trisomy 18, 19 carried trisomy 13, 1 carried trisomies 18 and 21. Eighty eight women accepted invasive prenatal diagnosis. The results of CMA in 59 cases were consistent with those of NIPT, which yielded a consistency rate of 67.05%. In addition, 37 cases of fetal CNVs were detected by NIPT, of which 19 (15 microdeletions and 4 microduplications) have accepted invasive prenatal diagnosis. In 14 cases, the results were consistency with those of NIPT, with a consistent rate of 73.68%. CONCLUSION NIPT features high sensitivity and accuracy. Invasive prenatal diagnosis should be considered for CNVs detected by NIPT, and by tracing its parental origin, it can provide guidance for clinical practice.
Chromosomes ; DNA Copy Number Variations ; Female ; Fetus ; Humans ; Pregnancy ; Prenatal Diagnosis ; Trisomy/genetics*

Objective:To investigate the value of renal glucose threshold and related factors in patients with type 2 diabetes mellitus.Methods:According to the cut-off point of normal renal glucose threshold(RT G 8.9-10 mmol/L), 107 patients with type 2 diabetes mellitus hospitalized in the Endocrinology Department of our hospital were divided into three groups: high RT G group(RT G>10 mmol/L), medium RT G group(8.9 mmol/L≤RT G≤10 mmol/L), and low RT G group(RT G<8.9 mmol/L). The clinical data and biochemical characteristics of each group were collected and analyzed. Results:The proportions of patients with high, medium, and low RT G of type 2 diabetes mellitus were 56%, 29%, and 15%, respectively. There were significant differences in RT G value, age, course of disease, body mass index(BMI), fasting plasma glucose(FPG), HbA 1C, total cholesterol(TC), serum creatinine, mean blood glucose(MBG), and 24-hour urine glucose between high and medium RT G groups. RT G, gender, BMI, FPG, HbA 1C, TC, and MBG in patients with high RT G group were different from those in low RT G group. Only RT G revealed a difference between medium and low RT G groups. Correlation analysis showed that RT G was positively correlated with gender, age, BMI, HbA 1C, TC, and low density lipoprotein-cholesterol(LDL-C). Regression analysis showed that BMI, HbA 1C, and LDL-C were the related factors affecting the RT G of patients with type 2 diabetes. Conclusion:There is a larger proportion of patients with high RT G in type 2 diabetes mellitus. Their BMI, HbA 1C, and LDL-C are associated with RT G in the patients with type 2 diabetes mellitus.

Objective:To investigate the changes of liver spin-lattice relaxation time (T 1rho) values in the rotating frame in the progression and regression of carbon tetrachloride (CCl 4)-induced model rats with liver fibrosis and the diagnostic values for staging liver fibrosis. Methods:Eighty rats were prospectively enrolled and randomly divided into the CCl 4 group ( n=49), the regression group ( n=20) and the control group ( n=11). All rats were labeled and then examined using MRI at baseline. The liver fibrosis model was established by subcutaneous injection of 40% CCl 4 in hackles. The CCl 4 group underwent black-blood T 1rho imaging at the end of the 4th, 6th, 8th, 10th, 12th week post CCl 4 injection. The regression group underwent black-blood T 1rho imaging at the end of the 4th, 6th week post CCl 4 injection and the end of 1st, 2nd, 4th, 6th week post CCl 4 withdrawal (the injection was stopped at the end of the 6th week). The control group was injected with the same amount of corn oil at the same time point and underwent black-blood T 1rho imaging at the end of 4th, 6th, 8th, 10th, 12th week. The liver T 1rho values were measured in each group over time. Independent-samples t test was used to analyze the differences of liver T 1rho values in adjacent time points. The experimental mice were divided into no liver fibrosis group (S0), mild liver fibrosis group (S1, 2) and moderate or severe liver fibrosis group (S3, 4). The differences of liver T 1rho values were analyzed in different fibrosis stages by Kruskal-Wallis H test. The receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic ability of T 1rho values in staging liver fibrosis. The correlation between liver T 1rho values and fibrosis stages was analyzed using Spearman correlation coefficient. Results:Fifty-nine rats completed the whole experiment, including 28 rats in the CCl 4 group, 20 rats in the recovery group and 11 rats in the control group. In the CCl 4 group, the liver T 1rho values gradually increased, reached the maximum at the end of week 8, and then gradually decreased. There was statistically significance in liver T 1rho values at the adjacent time points ( P<0.05) except at the 4th to 6th week ( P=0.112) and 10th to 12th week ( P=0.487) in the CCl 4 group. In regression group, the liver T 1rho values gradually increased post CCl 4 injection and decreased post CCl 4 injection withdrawal. There was statistically significance in liver T 1rho values at the adjacent time points ( P<0.05) in regression group. There was no statistically significance in liver T 1rho values at the adjacent time points ( P>0.05) in control group. The T 1rho values in the no liver fibrosis group (S0, n=15), the mild liver fibrosis group (S1, 2, n=23) and the moderate or severe liver fibrosis group (S3, 4, n=21) were [36.3(34.4,41.4)], (47.2±8.4), (48.8±9.0) ms, respectively. The liver T 1rho values increased with the aggravation of the liver fibrosis, and there was a low positive correlation between them ( r=0.402, P=0.001). There were statistically significant differences in T 1rho values among the three groups ( P<0.01).The area under the curve values to distinguish no liver fibrosis (S0) from liver fibrosis (S1 to 4) and no or mild liver fibrosis (S0 to 2) from moderately or severe liver fibrosis (S3,4) were 0.825 (95% confidence intervals is 0.720 to 0.931) and 0.668 (95% confidence intervals is 0.540 to 0.796), separately. Conclusion:The liver T 1rho values are useful for evaluating the progression and regression of liver fibrosis. It has a moderate diagnostic value to assess the presence of liver fibrosis, but a low diagnostic value to differentiate no or mild liver fibrosis from moderately to severe liver fibrosis.