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 investigate the expression of triple motif protein 21 (TRIM21) at different time points in Cisplatin induced acute kidney injury (Cis-AKI) mouse model and its correlation with pathological score . Methods: Acute kidney injury (AKI) model was induced by intraperitoneal injection of cisplatin (20 mg/kg) . Peripheral blood serum was collected at 12 , 24 , 48 and 72 h , respectively . Body weight and kidney mass were also recorded . The dynamic changes of serum creatinine ( SCr) and urea nitrogen ( BUN) were detected . The expressions of TRIM21 protein and endoplasmic reticulum stress (ERS) proteins GRP78 , GRP94 , P-elf2αand CHOP were de- tected by Western blot. HE staining was used to observe the pathology of renal tissue and analyze the correlation between the expression of TRIM21 protein at different time points . Results: Compared with the control group , the renal body ratio of Cis-AKI mice significantly increased at 48 h and 72 h (P < 0. 01) . SCr and BUN of Cis-AKI mice significantly increased at 48 h and 72 h compared with control group ( P < 0. 01) . HE staining showed that compared with the control group , the renal pathological scores of Cis-AKI mice increased at 12 and 24 h ( P < 0. 000 1) . At the same time , the expression of TRIM21 protein significantly increased at 24 h (P < 0. 01) . Com- pared with the control group , the renal pathological score of Cis-AKI mice significantly increased at 48 h ( P < 0. 000 1) , and the protein expression of TRIM21 , CHOP and GRP78 was significantly up-regulated at 48 h (P < 0. 05) . Compared with the control group , the renal pathological score of Cis-AKI mice significantly increased at 72 h (P < 0. 000 1) , and the expression of TRIM21 , GRP94 and P-elf2αproteins was significantly up-regulated at 72 h (P < 0. 05) . The results of correlation analysis showed that the expression of TRIM21 protein at different time points was positively correlated with the HE pathological scores at different time points (P < 0. 000 1) . Conclusion At different time points , TRIM21 may participate in the pathological progression of Cis-AKI by affecting ERS ,and it is positively correlated with renal pathological scores , which is expected to become a potential early diagnos- tic marker and intervention target.

Objective: To establish an in vitro cell model of Cobalt dichloride(CoCl2)-induced epithelial-mesenchymal transition(EMT) in rat renal tubular epithelial cells(NRK-52E). Methods: NRK-52E cells were cultured in vitro and randomly divided into a blank control group(NC group) and a CoCl2 treatment group. The CoCl2 treatment group underwent 1, 2, 3, and 4 cycles of treatment, with each cycle consisting of CoCl2 treatment for 9 h followed by recovery in CoCl_2-free medium for 3 h. The optimal concentration and time of CoCl_2-induced EMT were screened using the CCK-8 assay. Morphological changes in cells were observed using light microscopy and phalloidin staining. The expression levels of EMT marker proteins were detected by Western blot and immunofluorescence. Results: Compared with the NC group , stimulation by 100 μmol/L CoCl2 for 48 h significantly induced apoptosis (P < 0. 01) , meeting the requirements for subsequent experiments. Western blot results showed that the expression of hypoxia-inducible factor-1 α (HIF-1α ) and α-smooth muscle actin ( α-SMA) significantly increased in the 3-cycle group treated with 100 μmol/L CoCl2 for 9 h followed by recovery for 3 h ( P < 0. 001) , indicating the most pronounced fibrotic response. Observations under light microscopy and rhodamine-labeled phalloidin staining revealed that the morphological changes and cytoskeletal rearrangement of NRK-52E cells were most significant in the 3-cycle group treated with 100 μmol/L CoCl2 for 9 h followed by recovery for 3 h , demonstrating the best model stability. Immunofluorescence results showed that compared with the NC group , the fluorescence intensity of the fibrous matrix protein Collagen I significantly increased in the 3-cycle group treated with 100 μmol/L CoCl2 for 9 h followed by recovery for 3 h ( P < 0. 001) . Conclusion The protocol involves treating NRK-52E cells with 100 μmol/L CoCl2 for 9 h , following 3 h of recovery in CoCl2 -free medium. Repeating this cycle three times can establish an in vitro EMT model.

Objective To compare TyG index between the patients with CHF and ADHF to eluci-date the metabolic difference between these two stages.Methods A total of 1156 HF patients ad-mitted in Taizhou People's Hospital between January 2020 and December 2022 were enrolled,and according to 2021 ESC Guidelines for Diagnosis and Treatment of Acute and Chronic Heart Fail-ure,they were divided into CHF group(365 cases)and ADHF group(791 cases).The clinical da-ta,results of laboratory tests,and cardiovascular history were collected,and TyG index was calcu-lated.All-cause death outcome was observed in ADHF patients during a follow-up of 1 year.Results The TyG index was significantly lower in the ADHF group than the CHF group[8.27(7.99,8.62)vs 8.35(8.04,8.75),P=0.001].In the ADHF group,the TyG index was positively correlated with SBP,DBP,TC,TG,LDL-C,FPG,HbA1c,BMI,and LVEF,and negatively with age(P＜0.01).In the CHF group,the index was positively correlated with DBP,TC,TG,LDL-C,FPG,BMI,and HbA1c,and negatively with age(P＜0.05,P＜0.01).Both univariate and multiva-riate logistic regression analyses indicated that the TyG index was a protective factor for ADHF(OR=0.647,95％CI:0.503～0.832,P=0.001;OR=0.694,95％CI:0.536～0.898,P=0.005).Multivariate logistic regression analysis showed that the index in ADHF patients was a protective factor for one-year all-cause mortality(OR=0.483,95％CI:0.254-0.916;P=0.026).Conclusion TyG index might be regarded as an important marker for assessing the metabolic status in HF patients and predicting the prognosis in ADHF patients.

Objective:To establish a prognostic model and explore its clinical application based on disease progression within 24 months(POD24)in patients with multiple myeloma(MM).Methods:A total of 289 patients newly diagnosed with MM at Wuxi People's Hospital from January 2007 to June 2022 were selected as the training group for retrospective analysis.A prognostic model based on POD24 was constructed using Cox univariate and multivariate analyses of overall survival(OS).A total of 184 patients from The First Affiliated Hospital of Soochow University from August 2015 to December 2019 were included in the validation group to verify the predictive efficacy of the model.Results:Age,β2-microglobulin,Calcium,and POD24 were independent prognostic factors for MM.Patients in the high-risk group(≥2 points)had shorter OS(25.0 months vs.60.0 months)and progression-free survival(PFS)(14.0 months vs.56.0 months)than those in the low-risk group(<2 points).In addition,OS and PFS differed between the high-and low-risk groups in the entire validation group,as well as in each patient subgroup(P<0.05).Conclusions:The prognostic model based on POD24,age,β2 microglobulin,and Calcium holds prognostic value for patients newly diagnosed with MM in clinical practice.

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 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.