OBJECTIVES: To investigate genotype-phenotype characteristics and long-term prognosis of neonatal carbamoyl phosphate synthetase 1 (CPS1) deficiency among children through newborn screening in Zhejiang province. METHODS: The clinical and follow-up data of children with CPS1 deficiency detected through neonatal screening and confirmed by tandem mass spectrometry and genetic testing in Zhejiang Province Newborn Disease Screening Center from September 2013 to August 2023 were retrospectively analyzed. RESULTS: A total of 4 056 755 newborns were screened and 6 cases of CPS1 deficiency were diagnosed through phenotypic and genetic testing. Ten different variations of CPS1 genewere identified in genetic testing, including 2 known pathogenic variations (c.2359C>T and c.1549+1G>T) and 8 unreported variations (c.3405-1G>T, c.2372C>T, c.1436C>T, c.2228T>C, c.2441G>A, c.3031G>A, c.3075T>C and c.390-403del). All patients had decreased citrulline levels (2.72-6.21 μmol/L), and varying degrees of elevated blood ammonia. The patients received restricted natural protein intake (special formula), arginine and supportive therapy after diagnosis, and were followed-up for a period ranging from 9 months to 10 years. Three patients experienced hyperammonemia, and one patient each had attention deficit hyperactivity disorder, transient facial twitching and increased muscle tone. One patient died, while the other five surviving patients had normal scores of the Ages & Stages Questionnaires (ASQ) and Griffiths Development Scales up to the present time; 4 cases had combined height or weight lag and one case was normal in height and weight. CONCLUSIONS Low citrulline levels and hyperammonemia are common in CPS1 deficiency patients in Zhejiang. Most gene variants identified were specific to individual families, and no hotspot mutations were found. Early diagnosis through newborn screening and following standardized treatment can significantly improve the prognosis of the patients.
Child ; Humans ; Infant, Newborn ; Carbamoyl-Phosphate Synthase I Deficiency Disease/therapy* ; Neonatal Screening ; Follow-Up Studies ; Hyperammonemia ; Citrulline/genetics* ; Retrospective Studies ; Mutation

Objective:To investigate the characteristics of early myocardial mechanics changes in diabetic cardiomyopathy (DCM).Method:Sixty healthy 4-week-old male C57BL/6J mice were randomly divided into the T2DM group ( n=30) and the control group ( n=30). The T2DM group was fed with high-fat diet for 4 weeks, and accepted injection of a single high-dose of streptozotocin (STZ) intraperitoneally. Finally, the model was established successfully in 23 mice. The control group was fed with a normal diet and treated with citrate buffer liquid at an equal dose as T2DM group. Then, nine mice were randomly selected from each of the two groups every 4 weeks until the end of the 24th week. Six of the nine mice were randomly selected to perform 7.0 T MR scanning after measuring blood glucose and body weight. Cine images were acquired through cardiovascular MR feature tracking (CMR-FT). The obtained parameters included the left ventricle global peak circumferential strain (LV-GPCS), left ventricle global peak radial strain(GPRS) and the ejection fraction (EF), etc. The rest three mice were sacrificed for observation of the changes of interstitial fibers and micro-vessels in myocardial tissue with Sirius red staining. One-way analysis of variance (ANOVA) and t test were used for comparison. Results:There were significant differences in blood glucose levels between the two groups during the observation period ( P<0.05). In the 4 th-24 th week, the value of GPCS in T2DM group showed a downward trend, and the difference was statistically significant ( F = 8.23, P<0.001). Compared with the control group, the value of GPCS in T2DM group was statistically significant at the 20 th and 24 th week (the 20 th week: -11.4%±2.1% in the T2DM group vs. -14.3%±1.9% in the control group, t=2.54, P=0.029;the 24 th week: -12.3%±1.7% in the T2DM group vs. -14.6%±1.8% in the control group, t=2.35 , P=0.040), while the EF value was different at the 24 th week (51%±5% in the T2DM group vs. 62%±6% in the control group, t=3.38, P=0.007). There was no significant difference in the GPRS of the T2DM mice group over time or compared with the controls ( P>0.05). Moreover, the pathological results showed that the myocardial interstitial fibers in the T2DM group had remarkably increased since the 12 th week. Conclusions:The alterations in myocardial interstitial fibers and myocardial contractility appeared early in T2DM mice. Especially, the left ventricle global peak circumferential strain value is superior to the EF value in reflecting the early changes in DCM.

Objective:To evaluate the feasibility and diagnostic efficacy of the coronary fractional flow reserve derived from CT (CT-FFR) measurement method based on tracer pharmacokinetic principle.Methods:A total of 130 patients (159 coronary artery vessels) who were admitted to Beijing Anzhen Hospital from January 2015 to March 2019 were included in this study retrospectively. All patients had completed coronary CT angiography (CCTA) and invasive coronary angiography with invasive FFR. Subjective assessment of stenosis degree was performed on CCTA images and non-invasive FFR measurement was performed by using a tracer-kinetics based on CT-FFR measurement method. The Bland-Altman method was used to evaluate the diagnostic consistency of the two methods. Compared with the invasive FFR results, the sensitivity, specificity, positive predictive value, negative predictive value, and area under the ROC curve (AUC) of tracer-kinetics based on CT-FFR results for the diagnosis of coronary ischemic lesions were evaluated. All cases were divided into two heart rate groups:>65 bpm and ≤65 bpm. The diagnostic efficacy of tracer-kinetics based on CT-FFR in different heart rate groups was evaluated. χ 2 test and DeLong test were used to compare diagnostic performance in different evaluation methods and heart rate groups. Logistic regression analysis was used to evaluate the impact of factors such as heart rate, image thickness, image enhancement, and noise on the accuracy of diagnosis. Results:Bland-Altman analysis showed that the average difference between the two methods was -0.01. (-0.11-0.10). Compared with invasive FFR results, the tracer-kinetics based on CT-FFR method had a diagnostic sensitivity of 92.4%, specificity of 82.1%, positive predictive value of 87.6%, negative predictive value of 88.7%, and the area under ROC curve (AUC) value was 0.94. Compared with the diagnostic efficacy of luminal stenosis evaluated based on CCTA images, the difference was significantly statistical ( P<0.05). The diagnostic performance of CT-FFR had no statistically significant difference between the two heart rate groups. Factors such as heart rate, image thickness, image enhancement, and noise had no significant effect on the diagnostic accuracy of the tracer-kinetics based on CT-FFR method. Conclusions:The tracer-kinetics based on CT-FFR method may quickly complete the non-invasive FFR measurement on CCTA images with image quality that meets the needs of clinical diagnosis. It has a good diagnostic performance in the diagnosis of coronary ischemic lesions even for those cases with a faster heart rate. The diagnostic accuracy of tracer-kinetics based on CT-FFR method is not significantly affected by factors such as heart rate, image thickness, image enhancement, and image noise.

Objective To evaluate the feasibility and accuracy of cardiac CT (CCT) in quantitation of extracellular volume (ECV) fraction in patients with heart failure, with 3 T Cardiac MR (CMR) as the reference. Methods Twenty?eight patients with variety reasons of heart failure were enrolled in this study. ECVs was calculated, the correlation between CCT and CMR ECV value and other cardiac function parameters (left ventricular end systolic volume LVESV, left ventricular end diastolic volume LVEDV, cardiac output CO and ejection fraction LVEF, and clinical bio?marker BNP) was determined. Interclass correlation coefficient (ICC) was used to evaluate the agreement of measurement by two radiologists. Results The average of ECV on CCT and CMR was 33% ± 8% and 31% ± 6%, respectively. A good correlation was revealed between myocardial ECV at CCT and that at CMR (r=0.854, P<0.001). Bland?Altman analysis between CCT and CMR showed a small bias (4.6%), with 95% limits of agreement of-18.2% to 27.4%. ICC for ECV at CCT was excellent (ICC=0.910). For both CCT and CMR, ECV was inversely related to LVEF. The radiation dose for CCT?ECV was (1.60±0.04) mSv. Conclusions ECV at CCT and that at CMR showed good correlation, suggesting the potential for myocardial tissue characterization using CCT. However, CCT?ECV would possibly overestimate the extent of ECV.

Objective To analyze the correlation between calcification factors and fractional flow reserve derived from CT (CT?FFR). And to evaluate the diagnostic efficacy of CT?FFR in coronary artery lesions with calcification compared with that of invasive FFR. Methods Sixty?five patients (74 coronary artery vessels) who were admitted to Beijing Anzhen Hospital from July 2014 to December 2016 were included in this study retrospectively. All patients had completed CCTA (coronary CT angiography), coronary angiography and invasive FFR measurements, and had coronary lesions contain calcifications. The evaluation of CCTA data included quantitative analyses of plaque components, coronary artery stenosis, and CT?FFR measurements. The patients′basic data were grouped and compared according to the FFR values. The measurement data was tested by independent?samples t tests, and the categorical data were analyzed by χ2 tests. Quantitative measurements of plaques were compared between groups using independent?sample t tests or rank sum tests based on FFR and CT?FFR values. The reproducibility of CT?FFR measurement software was evaluated by inter?class correlation coefficient (ICC) and the Youden index was calculated to determine the threshold for CT?FFR diagnosis of ischemia. Pearson or Spearman correlation analyses were used to assess the correlations between CT plaque quantitative indicators, CT?FFR and invasive FFR. Multivariate logistic regression analysis was used to analyze the predictors of ischemia by FFR and CT?FFR. In contrast to invasive FFR results, the sensitivity, specificity, negative predictive value, positive predictive value (PPV) of CT?FFR in the diagnosis of coronary ischemic lesions were evaluated, and the diagnostic consistency was evaluated by the Bland?Altman method. Results Compared with invasive FFR, CT?FFR had a more significant correlation with calcification volume and ratio of calcification in plaques (r=-0.519 and－0.547, respectively, both P=0.001). Multivariate logistic regression analysis showed that plaque length was a predictor of invasive FFR in the diagnosis of pathological ischemia ( OR=1.13, 95%CI : 1.05—1.23, P=0.002), and was associated with CT?FFR to determine pathological ischemia. In addition to plaque length ( OR=1.10, 95%CI : 1.02—1.18, P=0.010), the predictor also included ratio of calcification in plaque ( OR=1.09, 95%CI: 1.03—1.15, P=0.003). Compared with invasive FFR results, the diagnostic sensitivity of CT?FFR was 79.1%, the specificity was 80.6%, the PPV was 85.0%, and the area under the ROC curve was 0.78. The result for the diagnosis of ischemia lesion by using CT?FFR had significant statistical differences with the results by according coronary artery stenosis (χ2=10.05, P=0.002; χ2=34.71, P=0.001; χ2=7.65, P=0.006; Z=2.10, P=0.029). The Bland?Altman analysis showed a mean difference of －0.01 (-0.26—0.25) between the CT?FFR and the invasive FFR. Conclusions There is no significant correlation between the proportion of calcification components of coronary plaque and the presence or absence of myocardial ischemia, but the proportion of calcification in plaque will affect the result that is evaluated by CT?FFR. However, compared with CT?based stenosis evaluation, CT?FFR can still significantly improve the ability of CCTA to diagnose ischemia lesion with calcification.

Objective To investigate the value of phase-contrast magnetic resonance imaging (PC-MRI)in evaluating pulmonary artery blood flow and right ventricular(RV)function in elderly patients with chronic obstructive pulmonary disease (COPD).Methods Twenty-four elderly patients with COPD admitted to Beijing Anzhen Hospital between February 2016 and June 2017 were enrolled in this retrospective study.Based on pulmonary artery pressure evaluated by right heart catheterization,COPD patients were divided into a pulmonary hypertension group (PH group,n =12)and a non-PH group(n=12).Pulmonary artery blood flow velocity and volume,pulmonary arterial compliance and right heart function parameters including ejection fraction,end diastolic volume,endsystolic volume and cardiac output,and 6-min walking distance evaluated by PC-MRI were compared between the two groups.Results There were significant differences in peak flow velocity[(88.1 ±16.0)cm/s vs.(59.8± 13.8) cm/s,P =0.005],flow volume [(80.7± 22.0) ml/s vs.(53.2± 26.7)ml/s,P=0.012],main pulmonary artery compliance[(42.3± 14.6)vs.(22.7± 10.8),P =0.001],right ventricular ejection fraction [(48.4 ± 13.4) ％ vs.(37.6 ± 11.1) ％,P =0.000],end-diastolic volume[(64.6±22.5)ml vs.(72.5±22.8)ml,P =0.030]and end-systolic volume[(50.6±33.1)ml vs.(41.7±33.1)ml,P =0.040]between the non-PH and PH groups,while there was no significant difference in cardiac output between the non-PH and PH groups[(34.2±10.8)ml vs.(34.4±8.3)ml,P =0.080].Pearson's correlation analysis showed that 6-minute walking distance had good correlations with right ventricular ejection fraction(r =0.49),forced expiratory volume in 1 s(FEV1)(r=0.60)and main pulmonary artery diameter(r=0.61).Conclusions PC-MRI is a noninvasive imaging method for quantitative analysis of pulmonary artery dynamics and right heart function for the elderly with COPD,and it can provide information for evaluating therapeutic effects and prognosis.

Objective To observe the value of optimized temporal parallel acquisition technique (TPAT) sequence in evaluating cardiac structure and function in arrhythmia patients.Methods Totally 33 arrhythmia patients (arrhythmia group) and 48 normal rhythm subjects (normal group) underwent cardiac MRI with conventional cine (balanced steadystate free-precession [bSSFP]) sequence and optimized TPAT sequence.Myocardial thickness,cardiac function,myocardial strain parameters of left ventricle and image quality of 2 sequences were compared in the two groups,respectively.Results In arrhythmia group,there was statistical difference of myocardial thickness in 12 myocardial segments between the 2 sequences (all P ＜ 0.05),as well as peak and average values of myocardial radial and circumferential strain (all P＜0.05).In normal group,there was no statistical difference of myocardial thickness and stain parameters between the 2 sequences (all P＞0.05).Additionally,no statistical difference of cardiac function was found between the 2 sequences in two groups (all P＞0.05).In arrhythmia group,the image quality of optimized TPAT sequence was better than that of bSSFP sequence (P＜0.05).Conclusion For arrhythmia patients,optimized TPAT cine sequence could improve image quality of cardiac MRI.

Objective Cardiac MRI is the "gold standard" for non-invasively assessing the structure and function of the heart.Compared with conventional cine imaging,MR strain technique can identify the abnormalities of segmental myocardial motion of heart diseases in the early stage by quantifying the displacement of myocardial tissue,which is of great value in evaluating the disease condition as well as guiding treatment and assessing prognosis.Myocardial strain can quantify the segmental wall motion,which is less impacted by other factors.The application of MR strain imaging in cardiac diseases were reviewed in this paper.

Objective To compare the diagnostic accuracy of clinically significant prostate cancer by general radiologist and uroradiology specialist based on the Prostate Imaging Reporting and Data System (PI-RADS).Methods A total of 45 men from Beijing United Family Hospital and Clinics undergoing prostate mpMRI examination and subsequent MRI-targeted biopsy were included in the study.The age of patients was (60.0 ± 8.0) years,the median PSA level was 7.2 ng/ml (1.2-95.8 ng/ml) and the median prostate volume was 45.0 ml (18.3-127.0 ml).The general radiologists from Beijing United Family Hospital and Clinics made the diagnosis according to PI-RADS 2.0.One uroradiology specialist from Beijing Anzhen hospital reviewed all the mpMRIs retrospectively and marked new PI-RADS score based on PI-RADS 2.0.The PI-RADS ≥ 3 lesion was recognized as suspicious of clinically significant prostate cancer.The distribution of PI-RADS score from different doctors and the diagnostic accuracy of clinically significant prostate cancer was compared.Results All the 45 patients underwent MRI-targeted cognitive biopsy and 14 cases of prostate cancer were detected,including 9 cases of clinically significant prostate cancer.There was no significant difference in the distribution of PI-RADS by general radiologist and uroradiology specialist (P =0.064).82.8％ (37/45) and 37.8％ (17/45) patients were diagnosed with PI-RADS ≥ 3 by general radiologist and uroradiology specialist respectively.The interobserver agreement was only 17.8％ (8/45).The positive predictive value of PI-RADS≥3 was 35.1％ (13/37) and 76.5％ (13/17) for prostate cancer by general radiologist and uroradiology specialist respectively,and for clinically significant prostate cancer,the positive predictive value of PI-RADS ≥ 3 was 21.6％ (8/37) and 52.9％ (9/17) respectively.Conclusions Uroradiology specialist achieved significantly superior in predictive value of PI-RADS for clinically significant prostate cancer compared with general radiologist.In the experienced centers,MRI-targeted biopsy could be performed only on high PI-RADS score lesions,thus to reduce unnecessary biopsies and to avoid over diagnosis and over treatment of prostate cancer.

Objective To analyze the impact of dual energy monochromatic reconstructions (50-160 keV) on coronary calcified plaque stenosis quantification in a cardiac phantom with the real stenosis as standard of reference.Methods Signal-to-noise(SNR)and contrast-to-noise ratios(CNR)were calculated. In conventional 120 kV coronary CT angiography (CCTA) images as well as 12 monochromatic series(50-160 keV),luminal narrowing of calcified plaque was measured and compared to the real stenosis. Bland-Altman plots were performed to analyze the correlation of reference standard with conventional 120 kV and 12 monochromatic series (50-160 keV). The sensitivity, specificity, and accuracy of CCTA for detection of≥50% stenosis were calculated and receiver operating characteristic(ROC)curve was analyzed with the real stenosis as reference standard.Results The SNR and CNR were decreased with the increase of keV from 70 keV.The SNR and CNR of monochromatic imaging were lower compared with conventional 120 kV images(SNR:76.4±16.1;CNR:274.7±54.1)(P<0.05).The Bland-Altman plots presented a smaller measurement bias towards 90-160 keV than conventional 120 kV, and smallest measurement bias was revealed in 100-130 keV imaging(100-130 keV:bias 17.2% vs 120 kV:21.4%).Using the stenosis≥50% as cut-off value, the specificity were higher in the monochromatic series (70-160 keV) than conventional 120 kV CCTA.The specificity(75.0%)were the highest in the 120 keV and 130 keV images.The area under the ROC curve(AUC)of 90-130 keV(0.991-0.995)was higher than that in conventional 120 kV imaging (0.990). Conclusions The use of monochromatic imaging improves the overall accuracy of stenosis evaluation in coronary calcified plaques. Reconstructions at 100-130 keV for calcified lesions yielded the optimal results.