Objective: This prospective study evaluated the feasibility of chemical exchange saturation transfer (CEST) MRI for assessing disease activity in thyroid-associated ophthalmopathy (TAO). Materials and Methods: A total of 88 patients with active TAO, 76 with inactive TAO, and 30 healthy controls were enrolled. CEST MRI-derived magnetization transfer ratio (MTR) and MTR asymmetry (MTRasym) at 1 ppm, 2 ppm, and 3.5 ppm were calculated. Clinical data, MTR, and MTRasym values for the extraocular muscles (one representative muscle per eye, yielding two measurements per participant) were compared among the groups. Spearman’s correlation was used to examine associations between imaging parameters and the clinical activity score (CAS) in patients with TAO. Logistic regression analysis was used to identify independent associations between imaging parameters and disease activity in patients with TAO (active vs. inactive). Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic performance for discriminating active from inactive TAO. Results: Patients with active TAO showed lower MTR values (P < 0.001) and higher MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) (all P < 0.001) compared with those with inactive TAO. MTR was negatively correlated with CAS (r = -0.402; P < 0.001), while MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) were positively correlated with CAS (r = 0.369, 0.350, and 0.349, respectively;all P < 0.001). MTR and MTRasym (1 ppm) were independently associated with TAO activity. The areas under the ROC curve (AUCs) for MTR and MTRasym (1 ppm) in discriminating active from inactive TAO were 0.772 and 0.730, respectively. Combining MTR with MTRasym (1 ppm) significantly improved diagnostic performance compared with either parameter alone, achieving an AUC of 0.805 (P = 0.029 and 0.001). Conclusion MTR and MTRasym (1 ppm) were independently associated with TAO activity. Their combination further enhanced diagnostic performance in distinguishing active from inactive TAO, suggesting their potential as quantitative imaging biomarkers to guide treatment in patients with TAO.

Objective:To explore the genetic characteristics and pathogenesis for a child with mosaicism trisomy 21 and Congenital leukemia (CL).Methods:A child who was admitted to Ningbo Women and Children′s Hospital in March 2023 was selected as the study subject. A retrospective analysis was carried out on the clinical data, laboratory test results, immunophenotyping, and genetic characteristics of the child. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: EC2024-063).Results:Whole genome sequencing (WGS) revealed that the child has mosaicism trisomy of chromosome 21, with a ratio of approximately 74%. In addition, pathogenic copy number variations involving multiple OMIM genes that could explain his clinical phenotype were detected and rated as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). No pathogenic variant was detected with the GATA1 gene. Blood immune typing of the child conformed to the immunophenotype of acute myeloid leukemia. Conclusion:For children with trisomy 21, even in the absence of GATA1 gene variants, the occurrence of CL should be monitored, and early diagnosis and treatment are of great significance for improving the prognosis.

Objective:To explore the relationship between life events, anxiety, depression, and behavior problems in adolescents.Methods:From September to October 2022, the cluster sampling method was used to select 5 341 adolescents from 4 middle schools in Xinxiang urban area.The subjects and their parents were investigated by the adolescent self-rating life events check list (ASLEC), generalized anxiety disorder scale (GAD-7), patient health questionnaire (PHQ-9), and child behavior checklist (CBCL). SPSS 27.0 software was used for Spearman correlation analysis, and AMOS 28.0 software was used to construct the structural equation model.Results:The scores of anxiety, depression, and behavioral problems were 1 (0, 4), 1 (0, 4), and 3 (0, 10). The total score of life events was 5 (1, 13), and the dimensions scored as follows: interpersonal conflict 1 (0, 4), academic pressure 2 (0, 5), punishment 0 (0, 2), loss 0 (0, 0), health and adaptation problem 0 (0, 1), and others 0 (0, 2). There were positive correlations between life events and its dimensions, depression, anxiety and behavioral problems ( r=0.28-0.69, all P<0.01). In the overall population, anxiety and depression played parallel mediating roles in the impact of life events on behavior problems. Life events could positively predict anxiety ( β=0.68, P<0.01), and anxiety could positively predict behavior problems ( β=0.04, P=0.02). Life events could positively predict depression ( β=0.77, P<0.01), and depression could positively predict behavior problems ( β=0.18, P<0.01). The standardized total effect size of the impact of life events on behavioral problems was 0.622 (95% CI=0.564-0.675). The standardized direct effect size and indirect effect size were 0.460 (95% CI=0.374-0.539) and 0.162 (95% CI=0.108-0.218), accounting for 74.0% and 26.0%of the total effect, respectively. After stratification by gender, the results for male adolescents were consistent with the overall population, while the mediating effect of anxiety was not significant in the female adolescents. Conclusion:Life events can lead to anxiety and depression in adolescents, thereby increasing the risk of behavior problems.

OBJECTIVE: To investigate the role of telomerase reverse transcriptase (TERT) in alleviating doxorubicin (DOX)-induced cardiotoxicity. METHODS: (1) Cell experiments: rat H9c2 cardiomyocytes were divided into control group (CON group), null adenovirus transfection group (NC group), TERT overexpression adenovirus transfection group (TERT group), DOX group (treated with 1 μmol/L DOX for 12 hours), DOX+NC group, and DOX+TERT group (null adenovirus or TERT overexpression adenovirus were transfected for 24 hours and then treated with 1 μmol/L DOX for 12 hours). The mRNA expression of TERT in cardiomyocytes was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The level of mitochondrial membrane potential was detected by immunofluorescence. The expression levels of intracellular Bax, Bcl-2, microtubule-associated protein 1 light chain 3 (LC3) and p62 were detected by Western blotting. (2) Animal experiments: male C57BL/6 mice were randomly divided into a sham operation group (Sham group), DOX group (acute cardiotoxicity model was constructed by intraperitoneal injection of DOX 15 mg/kg), DOX+NC group and DOX+TERT group (modeled after transfection with airborne adenovirus or TERT overexpression adenovirus for 7 days). After 7 days of modeling, the area of myocardial fibrosis was detected by Sirius scarlet staining, and cardiac function was detected by echocardiography. RESULTS: (1) Cellular experiments: the mRNA expression level of TERT was significantly higher in the TERT group compared with the CON and NC groups. Compared with the CON group, the TERT mRNA expression level of cardiomyocytes in the DOX group and the DOX+NC group were significantly lower, the level of mitochondrial membrane potential was significantly lower, the protein expressions of Bax and LC3 were significantly increased, and the protein expressions of Bcl-2 and p62 were significantly decreased. No significant differences were found between the DOX group and DOX+NC group. Compared with the DOX group and DOX+NC group, the TERT mRNA expression level was increased in the DOX+TERT group (relative expression: 1.02±0.10 vs. 0.61±0.05, 0.54±0.03, both P < 0.05), the level of mitochondrial membrane potential was significantly increased (1.14±0.05 vs. 0.96±0.01, 0.96±0.01, both P < 0.05), the protein expressions of Bax and LC3 were significantly decreased, and the protein expressions of Bcl-2 and p62 were significantly increased (Bax/β-actin: 0.88±0.01 vs. 1.31±0.02, 1.26±0.01; LC3-II/I: 2.16±0.05 vs. 2.64±0.06, 2.58±0.02; Bcl-2/β-actin: 0.65±0.01 vs. 0.40±0.01, 0.41±0.01; p62/β-actin: 0.45±0.01 vs. 0.23±0.02, 0.29±0.01; all P < 0.05). (2) Animal experiments: compared with the Sham group, the percentage of myocardial fibrosis area was significantly increased and left ventricular ejection fraction (LVEF) and fractional shortening (FS) were significantly decreased in the DOX group and DOX+NC group. Compared with the DOX group and DOX+NC group, the percentage of myocardial fibrotic area was significantly decreased in the DOX+TERT group (%: 2.33±0.06 vs. 3.76±0.07, 3.87±0.06, both P < 0.05), and the LVEF and FS were significantly increased [LVEF (%): 67.00±1.14 vs. 54.60±1.57, 53.40±2.18; FS (%): 38.60±0.51 vs. 30.60±1.10, 30.00±0.71; all P < 0.05]. CONCLUSION Up-regulation of TERT expression can inhibit DOX-induced cardiomyocyte autophagy and apoptosis, attenuate DOX-induced myocardial fibrosis in mice, improve cardiac function, and thus alleviate DOX-induced cardiotoxicity.
Animals ; Doxorubicin/toxicity* ; Telomerase/metabolism* ; Myocytes, Cardiac/metabolism* ; Rats ; Male ; Cardiotoxicity ; Mice, Inbred C57BL ; Mice ; Membrane Potential, Mitochondrial ; Adenoviridae ; bcl-2-Associated X Protein/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Transfection ; Apoptosis

OBJECTIVE To establish a core competency evaluation system for drug clinical trial quality management personnel in China and validate its application. METHODS Based on the scope of work， responsibilities， and role positioning of quality management personnel in drug clinical trials， a preliminary draft of the core competency evaluation system was constructed through literature analysis and expert consultation. The draft was refined through a Delphi method involving 17 experts who provided feedback and revisions， ultimately forming a complete evaluation system. The developed system was applied to conduct electronic surveys from March to May 2024 among 110 quality management personnel from 38 drug clinical trial institutions， comparing their scores on indicator importance and self-assessed capabilities. RESULTS The response rate of both rounds of questionnaire survey was 100%， with Kendall’s W coefficients of 0.256 and 0.277 （P＜0.001 for both）， and an expert authority coefficient of 0.946. The finalized evaluation system for core competencies of clinical trial quality management personnel comprised 9 primary indicators， covering individual professional competence， communication skills， implementation condition verification， informed consent process review， clinical trial execution monitoring， adverse event disposal， reporting and documentation， trial record examination， trial report auditing， and inspection of other tasks， and 107 secondary indicators. Empirical research revealed significant discrepancies between importance scores and self-assessed competency scores across 70 indicators among 110 respondents （P＜0.05）. Indicators with relatively notable gaps between importance scores and self-assessed competency scores included in-depth understanding of Good Clinical Practice （GCP） requirements （0.34-point gap）， familiarity with national and institutional clinical trial inspection priorities （0.24-point gap），etc. CONCLUSIONS The indicator system constructed in this study has good scientificity and reliability. Clinical trial quality management personnel demonstrate deficiencies in multiple critical competencies， highlighting the urgent need for targeted training programs to enhance their overall professional capabilities.

Objective To investigate the effects of dapagliflozin on the risk of malignant ventricular arrhythmia(MVA)during hospitalization in patients with acute myocardial infarction(AMI).Methods A retrospective study was conducted to select patients with AMI who underwent percutaneous coronary intervention(PCI)in the department of cardiology of the Third Affiliated Hospital of Nanjing Medical University between January 2018 and November 2023.Clinical datas collected during hospitalization included demographics(gender,age),baseline vital signs(systolic blood pressure,diastolic blood pressure,heart rate),comorbidities(hypertension,diabetes mellitus),body mass index(BMI),smoking,alcohol consumption,ST segment elevation myocardial infarction(STEMI),Killip class≥3,laboratory parameters[white blood cell count(WBC),neutrophil percentage(NEU%),serum creatinine(SCr)],procedural data(number of coronary stents implanted,culprit vessels being the left main coronary artery,left anterior descending artery,right coronary artery,left circumflex artery and intraoperative hypotension),medications[angiotensin converting enzyme inhibitor/angiotensinⅡreceptor blocker(ACEI/ARB),β-blockers,aspirin,ticagrelor,clopidogrel,platelet glycoproteinⅡb/Ⅲa receptor antagonists,Statin],and electrocardiogram characteristics[the number of cases frequent ventricular premature contractions(premature beats)and the number of cases of sinus rhythm].The study endpoint was the occurrence of MVA during hospitalization among enrolled patients.Patients were categorized into the MVA group and the non-MVA group based on the occurrence of MVA during their hospital stay.Differences in clinical characteristics between the two groups were compared.Univariate and multivariate Logistic regression analyses were employed to evaluate the impact of dapagliflozin use on the risk of MVA in patients with AMI.Results A total of 2 893 eligible AMI patients were enrolled and 145 patients(5.01%)experienced MVA during hospitalization.Compared with the MVA group,the proportion of patients taking dapagliflozin was higher in the non-MVA group[13.2%(363/2 748)vs.6.2%(9/145),P=0.014],the proportion of males was higher[74.3%(2 042/2 748)vs.66.9%(97/145),P=0.048],the age was younger(years:64.82±13.91 vs.69.78±14.07,P<0.001),the heart rate at admission was slower(beats/min:80.09±15.72 vs.84.31±20.92,P=0.002),the proportion of patients with Killip grade≥3 was lower[11.5%(317/2 748)vs.38.6%(56/145),P<0.001],the proportion of smoking patients was higher[48.0%(1 319/2 748)vs.33.8%(49/145),P<0.05],SCr level was lower(μmol/L:84.73±58.52 vs.102.87±59.47,P<0.001),and the proportion of patients taking ACEI/ARB and β-blockers was higher[64.9%(1 783/2 748)vs.49.0%(71/145),65.1%(1 788/2 748)vs.53.8%(78/145),both P<0.05],the rate of frequent premature ventricular beats was lower[1.0%(28/2 748)vs.11.7%(17/145),P<0.05],and the proportion of patients with intraoperative hypotension was lower[3.2%(86/2 748)vs.10.6%(15/145),P<0.05].After adjusting numerous confounding factors,multifactorial Logistic regression analysis showed that dapagliflozin may significantly reduced the risk of MVA in patients with AMI after PCI[odds ratio(OR)=0.417,95%confidence interval(95%CI)was 0.200-0.880,P=0.022].Subgroup analysis suggested that there were 1 042 AMI patients with diabetes mellitus,of whom 348 took dapagliflozin,and 8 patients(2.30%)had MVA.The risk of MVA was reduced in patients taking dapagliflozin(Log-Rank:χ2=11.983,P=0.001).Conclusion The use of dapagliflozin significantly reduced the risk of MVA during hospitalization in patients with AMI.

Objective To observe the value of three-dimensional ultrasound combined with microvascular flow imaging for prenatal diagnosis of fetal intracranial anomalies.Methods Totally 118 fetuses with intracranial anomalies diagnosed through cranial MRI/induced labor specimen dissection who underwent prenatal ultrasound examination were retrospectively enrolled.Two-dimensional,three-dimensional ultrasound and microvascular flow imaging manifestations of fetal intracranial anomalies were observed,and the accuracy of three-dimensional ultrasound combined with microvascular flow imaging for prenatal diagnosis of fetal intracranial anomalies was analyzed.Results The accuracy of three-dimensional ultrasound combined with microvascular flow imaging for prenatal diagnosis of fetal intracranial anomalies was 93.22％(110/118),of isolated and non-isolated intracranial anomalies was 97.47％(77/79)and 84.62％(33/39),respectively.Six fetuses were missed diagnosis of malformations of cortical development(1 fetus of tuberous sclerosis,4 of abnormal morphology of the sulci gyrus and 1 of schizencephaly)and 1 fetus of intracranial softening lesion,while posterior fossa arachnoid cyst in 1 fetus was misdiagnosed as mega cisterna magna.Conclusion The accuracy of three-dimensional ultrasound combined with microvascular flow imaging for prenatal diagnosis of fetal intracranial anomalies was relatively high.

Objective To observe prenatal ultrasonic findings of fetal malformation of cortical development(MCD).Methods Totally 37 singleton fetuses with MCD diagnosed by fetal cranial MRI and/or genetic examination were retrospectively enrolled,and prenatal ultrasonic manifestations were observed.Results Among 37 fetuses,29(29/37,78.38％)were found with abnormal Sylvian fissure,26(26/37,70.27％)with widened/asymmetrical lateral ventricles,22(22/37,59.46％)with abnormal surface sulci,14(14/37,37.84％)with abnormal cavity of septum pellucidum(CSP)/corpus callosum(CC),11(11/37,29.73％)with midline deviation/curvature,11(11/37,29.73％)with widened subarachnoid space,10(10/37,27.03％)with head circumference＜2 standard deviation below mean value,9(9/37,24.32％)with abnormalities in the cerebellar hemisphere/vermis,7(7/37,18.92％)with abnormal echoes in the brain parenchyma,7(7/37,18.92％)with midline cysts and 2(2/37,5.41％)with enlarged ganglion eminence.Conclusion Fetal MCD mainly presented as abnormal Sylvian fissure,widened/asymmetrical lateral ventricles and abnormal surface sulci,which might accompanied by abnormal CSP/CC,midline deviation/curvature,widened subarachnoid space and abnormal head circumference in prenatal ultrasound.