ObjectiveTo screen key genes associated with neuroblastoma （NB） diagnosis and prognosis using the Gene Expression Omnibus （GEO） database， and to investigate the expression and clinical significance of nucleoporin 93 （NUP93） in NB tissues. MethodsNB gene chip data （GSE73517， GSE49710， GSE19274） were retrieved from the GEO database. Differentially expressed genes （DEGs） commonly upregulated in high-risk groups were screened. The R2 database was then used to assess the prognostic value of DEGs that were commonly upregulated in the MYCN amplification group. Finally， NUP93 expression levels in the tissues from 60 NB， 25 ganglioneuroblastoma （GNB）， and 26 ganglioneuroma （GN） cases were measured by immunohistochemistry . ResultsTwenty-five DEGs were identified as commonly upregulated in high-risk groups. Among these， 10 genes （SIVA1， NUP93， STIP1， LSM4， RAI14， MYOZ3， KNTC1， TNFRSF10B， TACC3 and CEP152） showed significantly higher expression in MYCN-amplified subgroups （P＜0.05）. Survival analysis revealed that high NUP93 expression was associated with shorter overall survival （HR = 4.0， 95% CI： 3.0，5.3， P = 1.80 × 10⁻³⁴）. Immunohistochemistry results revealed that NUP93 expression in NB tissues was significantly higher than in GNB and GN tissues （P＜0.001）. NUP93 expression was positively correlated with high mitosis-karyorrhexis index （MKI； P=0.040）， poor differentiation （P＜0.001）， and MYCN expression （r_s = 0.793， P ＜0.001）. ConclusionsHigh expression of NUP93 is associated with high MKI and poor differentiation， and predicts unfavorable prognosis in patients with NB， suggesting it may promote tumor progression by regulating MYCN. NUP93 has the potential to be a novel diagnostic biomarker and therapeutic target for NB.

Humans ; Amyloidosis ; Amyloid ; Cardiomyopathies

Objective To construct a non-trace deletion mutant of exlA in Pseudomonas aeruginosa strain NY8755(NY8755ΔexlA)and investigate the basic characteristics of pore-forming toxin ExlA.Methods The NY8755ΔexlA was constructed using the secondary homologous recombination method.C57BL/6J female mice ages 6 to 8 weeks were infected with NY8755 and NY8755 ΔexlA via aerosolized intratraheal inoculation respectively.Within 7 days of infection,the survival and weight changes of the mice were observed and recorded before the proinflammatory cytokines in the bronchoal-veolar lavage fluid(BALF)of the infected mice in the two groups were detected.Results The sequencing results showed that NY8755 ΔexlA was constructed.After 1×107 CFU NY8755 and NY8755 ΔexlA were infected,all the mice in the wild-type strain group died within 48 hours,while those in the mutant strain group began to die after 48 hours,and 40%of them remained alive 7 days later.The weight of surviving mice in the mutant strain group decreased but recovered gradually.After 12 hours of infection,there were more bloody exudates(redder in color)in the BALF of the wild-type strain group than in the mutant strain group,and the contents of proinflammatory cytokines interleukin-1β(IL-1β)and interleukin-17A (IL-17A)were significantly different. Conclusion Pseudomonas aeruginosa pore-forming toxin ExlA is the key pathogenic virulence factor of the exlA-positive Pseudomonas aeruginosa,which can significantly affect the survival status of mice and cause obvious inflammation in mice. Very little information is available on the action mechanisms of ExlA. In this study, The NY8755ΔexlA and the C57BL/6J mouse models infected with NY8755 and NY8755ΔexlA have been constructed that may be used for the investigation of pathogenesis of exlA-positive Pseudomonas aeruginosa.

Objective To investigate the relationship between sleep duration and obesity, and the risk of common chronic diseases in the occupational population in Shanghai City. Methods A total of 18 775 occupational individuals were selected as the study subjects using convenience sampling method in Shanghai City. Data on personal lifestyle behaviors and medical examination results were collected. The relationship between sleep duration and different types of obesity with dyslipidemia, hyperuricemia, hypertension, and hyperglycemia was analyzed. Results The incidence of dyslipidemia, hyperuricemia, hypertension, and hyperglycemia among the study subjects was 24.9%, 16.2%, 11.5%, and 7.3%, respectively. The incidence of these four chronic diseases were higher in individuals with central obesity and suboptimal sleep compared to the control group (all P<0.01). Multivariate logistic regression analysis showed that suboptimal sleep combined with general obesity/overweight increased the risk of dyslipidemia, hyperuricemia, hypertension, and hyperglycemia in the study subjects ［odds ratio (OR) were 2.40, 3.47, 3.30, and 2.79, respectively; all P<0.01］, after adjusting for age, gender, education level, marital status, occupation type, labor intensity, smoking, and drinking. Suboptimal sleep combined with central obesity also potentially increased the risk of these four chronic diseases (OR were 2.25, 3.09, 3.09, and 2.98, respectively; all P<0.01). Conclusion The incidence of common chronic diseases is relatively high in the occupational population in Shanghai City. Suboptimal sleep combined with different types of obesity increases the risk of common chronic diseases.

Objective:To explore the clinical value of cardiac MR (CMR) compression sensing (CS) ultrafast cine sequence in evaluating left and right ventricular systolic function by comparing with traditional segmented acquisition cine sequence (Seg).Methods:Twenty-seven patients with various heart disease were prospectively included. Seg, breath holding CS (bhCS) and free breathing CS (fbCS) covering the left and right ventricles using multi slices in short axis were performed in random order. Friedman test was used to evaluate the overall image quality (grade 1-5 score), blood pool myocardial signal ratio (BMC) and edge sharpness under different methods. Biventricular end diastolic volume (EDV), end systolic volume (ESV), stroke volume (SV), ejection fraction (EF) and left ventricular myocardial mass (Mass) were measured for all three methods. The agreements of the functional measurements between bhCS and Seg (gold standard), and between fbCS and Seg were analyzed by Bland-Altman, and the correlation test was performed.Results:Twenty-four patients with diagnostic images(overall image quality score≥2) for all three methods were included in further analysis. The total imaging time of Seg, bhCS and fbCS decreased successively[375.0 (332.0, 405.6) vs. 50.0 (47.8, 53.7) vs. 20.0 (17.8, 23.7) s, χ 2=48.00, P<0.001]. The overall image quality of fbCS was slightly lower than that of Seg ( Z=-2.67, P=0.023), and there was no difference between Seg and bhCS ( Z=-1.44, P=0.447), bhCS and fbCS ( Z=1.23, P=0.660). There were no differences in edge sharpness (χ 2=1.08, P=0.582) and BMC (χ 2=0.58, P=0.747) for three methods. Bland-Altman polts showed good agreement for biventricular functional measurements between bhCS and Seg, and between fbCS and Seg. All functional measurements of bhCS and fbCS were highly correlated with that of seg ( r>0.96, P<0.001). Conclusions:Compared with traditional sequences, CS ultrafast cine sequences can save scanning time and provide similar image quality. No matter whether breath holding or not, the cardiac functional results of CS sequence and traditional cine sequence have good agreement and high correlation.

Objective:To investigate the value of T 1ρ mapping in the assessment of myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM). Methods:Forty HCM patients and 16 healthy volunteers who underwent CMR examination between December 2021 and May 2022 were prospectively enrolled. T 1ρ mapping, pre-and post-contrast T 1 mapping, and gadolinium contrast-enhanced delayed enhancement (LGE) imaging were performed in HCM patients, while T 1ρ mapping and T 1 mapping were performed in volunteers. HCM patients were further divided into LGE-positive (LGE+) and LGE-negative (LGE-) groups based on the presence or absence of LGE. The T 1ρ and pre-contrast T 1 values of the left ventricular myocardium of HCM patients and volunteers were measured, and the extracellular volume fraction (ECV) of the left ventricular myocardium of HCM patients was measured using pre-and post-contrast T 1 mapping. One-way ANOVA was used to compare the T 1ρ and pre-contrast T 1 values among the LGE+, LGE-, and volunteer groups, and pairwise comparisons were further corrected using the Bonferroni method. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of pre-contrast T 1 and T 1ρ values in distinguishing LGE+ and LGE- patients from volunteers. The chi-square test or Fisher′s exact probability test was used for categorical variable comparisons. Pearson correlation coefficient was used to evaluate the correlation between T 1ρ and pre-contrast T 1, and ECV. Results:There were no significant differences in age, gender, and body surface area among the LGE+, LGE-, and healthy control groups ( P>0.05). Compared to the HC group, both the T 1ρ value ( t=5.74, P<0.001) and the pre-contrast T 1 value ( t=3.99, P<0.001) increased in LGE positive group, as well as in the LGE negative group (T 1ρ: t=4.19, P<0.001; T 1: t=2.06, P<0.044). ROC analysis showed that the area under the curve (AUC) of T 1ρ and pre-contrast T 1 in distinguishing LGE+patients from healthy controls were 0.93 (sensitivity 84.0%, specificity 93.8%) and 0.87 (sensitivity 84.0%, specificity 87.5%), respectively. The AUC of T 1ρ and pre-contrast T 1 in distinguishing LGE-patients from healthy controls were 0.84 (sensitivity 86.7%, specificity 68.8%) and 0.68 (sensitivity 60%, specificity 68.8%), respectively. The correlation analysis showed that the T 1ρ value of the left ventricular myocardium was positively correlated with the pre-contrast T 1 value ( r=0.31, P=0.02) and ECV value ( r=0.38, P=0.02). Conclusion:Without the use of contrast agents, T 1ρ mapping shows good performance for myocardial replacement fibrosis and diffuse fibrosis in HCM patients.

Objective:To investigate the clinical and cardiac magnetic resonance (CMR) characteristics of heart involvement in patients with Fabry disease (AFD).Methods:From January 2018 to March 2021, eight AFD patients [3 males and 5 females, mean age (50±11) years old, range 26-60 years old] confirmed by genetic testing or pathology in Fuwai Hospital were retrospectively included in this study. At the same time, sixteen patients with hypertrophic cardiomyopathy (HCM) [6 males and 10 females, mean age (46±15) years old] and 16 healthy individuals [6 males and 10 females, mean age (51±11) years old] were included as controls. The clinical baseline data and CMR data of the patients were collected and analyzed. The CMR data were analyzed using the software CVI42, with the corresponding parameters automatically generated. One-way ANOVA or Kruskal-Wallis test was used to compare the differences in the parameters among the three groups. Independent-samples t test, Fisher precise test or Mann-Whitney U test were used for the comparison between each two groups. Results:Statistically significant difference was found in renal insufficiency between the HCM group and the AFD group; No other significant difference was found in other clinical factors and ECG results (all P>0.05). CMR results showed that in the AFD group, there were 5 cases with symmetric or roughly symmetric hypertrophy, and 3 with asymmetric hypertrophy. The late gadolinium enhancement (LGE) showed myocardial enhancement in 5 patients, mainly presenting as multiple intermural enhancement, and partially as local subendocardial enhancement. In the HCM group, fourteen cases suffered mainly asymmetric ventricular septal thickening, with or without thickening of other parts of left ventricular wall; and 2 cases had thickening of middle and distal part of the left ventricle. The LGE showed myocardial enhancement in 14 patients, which manifested as focal or patchy enhancement in hypertrophic myocardium, including focal enhancement in the right ventricular insertion of ventricular septum (more common) and subendocardial enhancement in the middle and far segments of left ventricle. Statistically significant difference was found in the differences between the left atrial anterior posterior diameter, the maximum wall thickness of left ventricular, the left ventricular myocardial mass index (LVMI) and the native T 1 value among the three groups (all P<0.001). However, there was no statistically significant difference in the left atrial anterior posterior diameter and the maximum wall thickness of left ventricular between AFD group and HCM group ( P>0.05). The LVMI in AFD group was higher than that in healthy group and HCM group (all P<0.05). Significant difference was found in the native T 1 value among the three groups, with the native T 1 value of the AFD group [(1 177.4±46.0) ms] was significantly lower than that of the healthy group [(1 244.5±34.3) ms] and the HCM group [(1 278.8±41.6) ms], with ( F=13.10, P<0.001). Conclusions:The clinical characteristics of AFD and HCM are quite similar. When AFD is suspected, CMR imaging should be the first choice for imaging examination. Especially, T 1 mapping imaging can provide important information for the diagnosis of AFD.

Objective:To explore the clinical value of T 1 mapping/indexed extracellular volume fraction (iECV) quantified with cardiac MR (CMR) parameters, and its correlation with traditional indicators of myocardial dysfunction in aortic insufficiency (AI) patients. Methods:A total of 36 patients clinically and radiologically diagnosed with chronic AI in our hospital between May 2012 and February 2016 were retrospectively selected. All AI patients underwent conventional CMR protocol, native and post T 1 mapping. CMR parameters, such as aortic regurgitant fraction (RF), late gadolinium enhancement (LGE) mass fraction, myocardial extracellular volume fraction (ECV) and iECV. Based on the values of aortic RF, AI patients were divided into mild AI group (9 cases), moderate AI group (14 cases) and severe AI group (13 cases). The clinical characteristics were teased from the patients′ electronic medical records. Univariate analysis of variance was used to compare the measurement data of native T 1 mapping, post-contrast T 1 mapping, ECV, and iECV. LSD test was used for pair wise comparison between the mild AI, moderate AI and severe AI groups. Data about cardiovascular history, New York Heart Association (NYHA) heart function classification, and LGE were compared by chi-square test or Fisher exact test. The correlation between left ventricle ejection fraction (LVEF) and iECV was evaluated by Spearman correlation analysis. Results:There was no difference in age, sex, cardiovascular history among the three groups. Comparison of patients with different severity of AI in the three groups: (1) There was statistically significant difference in the LGE positive rate among the three groups ( P=0.023), while the myocardial replacement of fibrosis increased with the grade of aortic regurgitation. (2) There was no statistically significant difference in the measurement data of native T 1 mapping, post-contrast T 1 mapping, ECV among the three groups ( H=1.815, 0.929, 2.496, all P values>0.05), while the diffuse myocardial fibrosis tended to increase with the degree of aortic regurgitation. There was statistically significant difference in iECV among the three groups ( H=16.725, P<0.001). The measurement data of iECV in the severe AI group was significantly higher than those in the other two groups ( P<0.05). LVEF value was inversely correlated with iECV ( r=-0.649, P<0.001). Conclusions:Quantitative T 1 mapping/iECV can serve as a parameter to noninvasively identify diffuse myocardial fibrosis in AI patients of different severities. It changes with LVEF and can manifest the reversible stage of left ventricular decompensation.

Objective:To investigate the effect of edaravone, a free radical scavenger, on the regulation of retinal autophagy and the protection of photoreceptor cells at the early stage of experimental retinal detachment (RD) in rats.Methods:Fifty-one adult male Sprague-Dawley rats were used for RD model establishment, and another 24 rats were served as PBS injection group.The RD model was established via subretinal injection of 0.5% sodium hyaluronate into the right eye of the rats and the rats with successful modeling were randomly divided into RD model group and edaravone treatment group.The rats in the edaravone treatment group were given edaravone of 3 mg/kg intraperitoneally, twice a day after modeling, and the rats in the PBS injection group and RD model group were given equal volume of normal saline.Rats were sacrificed on the 1st day, 3rd day and 7th day following modeling.The T-superoxide dismutase (T-SOD) activity and malondialdehyde (MDA) content in the intraocular fluid was detected.The expression levels of superoxide dismutase 2 (SOD2), nuclear factor E2-related factor 2 (Nrf2), autophagy related gene 4 (Atg4), microtubule-associated protein 1 light chain 3B (LC3B) and other proteins in retinal tissue were identified by Western blot analysis.TUNEL staining was performed on paraffin sections of the whole eyeball to analyze the apoptosis of photoreceptor cells.The study protocol was approved by an Ethics Committee of Xi'an Fourth Hospital (No. 2016016). The use and care of animals complied with the Regulations on the Administration of Experimental Animals.Results:The RD area was more than 60% in rat eyes of RD model.There were significant differences in MDA content and T-SOD activity among different groups at various time points (MDA: Fgroup=385.513, P<0.01; Ftime=13.021, P<0.01.T-SOD: Fgroup=48.865, P<0.01; Ftime=7.700, P=0.003). Compared with the PBS injection group, the MDA concentration was significantly increased and the T-SOD activity was significantly decreased in the RD group and edaravone treatment group on the 1st, 3rd and 7th day after modeling (all at P<0.05). The MDA concentration was significantly reduced and the T-SOD activity was significantly elevated in the edaravone treatment group on the 1st, 3rd and 7th day after modeling in comparison with those of the RD group (all at P<0.05). Compared with the PBS injection group, the relative expression levels of SOD2 and Nrf2 proteins were significantly increased in the RD group and edaravone treatment group on the 1st, 3rd and 7th day after modeling (all at P<0.05), and Atg4 and LC3B-Ⅱ/LC3B-Ⅰ were significantly increased on the 1st, 3rd and 7th day after modeling (all at P<0.05). The expression level of SOD2 in the edaravone treatment group was significantly higher than that in the RD group on the 1st, 3rd and 7th day after modeling (all at P<0.05), and the expression level of Nrf2 was significantly increased in the edaravone treatment group on the 1st and 3rd day after modeling compared with that of the RD group (both at P<0.05), and the expression levels of Atg4 and LC3B-Ⅱ/LC3B-Ⅰ were significantly increased in the edaravone treatment group on the 3rd day after modeling in comparison with those of the RD group (both at P<0.05). No significant TUNEL positive cells were observed in PBS injection group at all time points, and TUNEL positive cells were observed on the 1st, 3rd and 7th day after modeling in the RD group, and the expression level of caspase-3 in the RD group was significantly increased in comparison with that of the PBS injection group ( P<0.05). The apoptosis of photoreceptor cells and the expression level of caspase-3 in edaravone treatment group were significantly decreased in comparison with those of the RD group on the 1st, 3rd and 7th day after modeling (all at P<0.05). Conclusions:The intraperitoneal injection of edaravone, twice a day, can significantly improve the antioxidant capacity of the retina after experimental RD in rats, regulate retinal autophagy and reduce the apoptosis of photoreceptor cells in early-stage RD.

Objective: To investigate the cardiovascular magnetic resonance (CMR) imaging characteristics and influence factors of aortic insufficiency (AI) patients with myocardial fibrosis. Method: This retrospective study included 59 AI patients who received CMR and transthoracic echocardiography (TTE) examinations from June 2011 to February 2015. AI patients were divided into 2 groups: bicuspid aortic valve (BAV) group (n=30) and non-BAV group (n=29). Patients were also divided into late gadolinium enhancement (LGE) group (n=27) and non-LGE group (n=32). The baseline clinical characteristics were collected through electronic medical records. Hemodynamic parameters such as grade of AI, cardiac functional parameters and LGE mass fraction (LGE%) were measured by CMR post-processing analysis. Kappa test was used to assess the consistency of AI severity between CMR and TTE, and the multivariate logistic regression analysis was performed to evaluate influence factors of myocardial fibrosis in AI patients. Results: (1) 56 (94.9%) patients were male, and the mean age was (44.2±11.0) years old. There was no significant difference in age and gender, hypertension, hyperlipidemia, alcoholic consumption between BAV and non-BAV group (all P>0.05). There were a higher proportion of smoking history (P=0.008), a lower body mass index (BMI) (P=0.020) in the LGE group than in the non-LGE group. (2) The accuracy of CMR in diagnosis of BAV was 96.7% (29/30) compared to the gold standard. In the BAV group, 20 patients (66.7%) were with fusion of left and right cusp (L-R), 5 patients (16.7%) were with fusion of right and noncoronary cusp (R-N), 5 patients (16.7%) were with fusion of left and noncoronary cusp (L-N); patients with BAV had larger left ventricular end diastolic volume index (LVEDVi), left ventricular end systolic volume index (LVESVi), higher proportion of LGE and lower left ventricular ejection fraction (LVEF) than those in non-BAV group (all P<0.05). There were 19 patients with BAV in the LGE group, the cases of L-R, R-N, L-N were 10 (52.6%), 5 (26.3%), and 4 (21.1%), respectively. In the non-LGE group, patients with BAV of L-R, R-N, L-N were 10 (90.9%), 0, and 1 (9.1%), respectively. Patients with LGE had lower body surface area (BSA), LVEF and larger LVEDVi, LVESVi, left ventricular mass index (LVMi) and higher proportion of BAV compared patients without LGE. In addition, the proportion of moderate and severe AI patients was significantly higher in BAV group than in non-BAV group (P=0.009). (3) The consistency of CMR and TTE in evaluating the severity of AI patients: the agreement between TTE and CMR regarding AI severity was satisfactory (kappa value was 0.624, 95%CI 0.402-0.831, P<0.001). (4) The linear regression analysis demonstrated a negative correlation between LVEF and LGE% in BAV and non-BAV group (P<0.001). The multivariate logistic regression analysis showed that the presence of BAV was an independent risk factor of left ventricucar fibrosis (OR=5.050, 95%CI 1.220-20.908, P=0.025) after adjustment for LVEF, hypertension, LVEDVi and LVMi. Conclusion Multi-parametric CMR provides a satisfactory noninvasive tool for estimation of myocardial fibrosis and ventricular remodeling in patients with AI, and BAV is an independent risk factor for myocardial fibrosis in patients with AI.