1.Screening and characterization of anti-SARS-CoV-2 receptor binding domain antibodies with broad-spectrum neutralizing activity
NI Wanqi ; REN Li ; JIN Changzhong ; YANG Furong ; SHEN Yumin ; WANG Shuo ; HU Caiqin ; HAO Yanling ; LIU Ying ; ZHU Biao ; SHAO Yiming ; LI Dan ; WANG Zheng
China Tropical Medicine 2024;24(3):258-
		                        		
		                        			
		                        			convalescents, and to screen for broad-spectrum neutralizing antibodies against the SARS-CoV-2 RBD. Methods    Using biotinylated RBD as a molecular probe, flow cytometry was employed to perform single-cell sorting of B cells from peripheral blood mononuclear cells (PBMCs) of convalescents. The obtained B cells were lysed and subjected to reverse transcription, followed by nested PCR amplification of the heavy and light chains of antibodies was conducted using random primers. The amplified products were cloned into corresponding expression vectors, and the respective matched heavy-light chain plasmids were co-transfected into 293F cells for expression. Monoclonal antibodies were then purified using Protein A column chromatography. Neutralization experiments were conducted with the wild-type (WT) pseudovirus, and antibodies with IC50<0.1 μg/mL were selected for further testing of neutralizing breadth and potency against the wild-type (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and currently prevalent pseudovirus strains (XBB, BA.5, BF.7). Results    A total of 21 RBD-specific monoclonal B cells were obtained from two recovered patients, resulting in the isolation of 13 pairs of antibody light/heavy chains. Nine antibodies were successfully expressed, with P1-A1, P1-B6, and P1-B9 exhibiting IC50 values below 0.1 μg/mL against the pseudovirus of the wild-type strain (WT). Specifically, P1-B6 effectively neutralized the wild-type strain (WT), Beta variant (B.1.351), and Delta variant (B.1.617.2), with IC50 values reaching 0.01 μg/mL. P1-B9 demonstrated effective neutralization against the wild-type strain (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and Gamma variant (P.1) pseudoviruses, with IC50 values of 0.42 μg/mL, 0.63 μg/mL, 0.28 μg/mL, and 2.50 μg/mL, respectively. Additionally, P1-B6 exhibited good neutralization against BA.5 and BF.7 pseudoviruses, with IC50 values of 0.06 μg/mL and 0.09 μg/mL, respectively. Conclusions    Infection with the SARS-CoV-2 WT strain can induce the generation of neutralizing antibodies with broad-spectrum activity. Generating these broadly neutralizing antibodies does not require an excessively high somatic hypermutation. The obtained antibodies can be used as candidates for SARS-CoV-2 diagnosis and prevention. 
		                        		
		                        		
		                        		
		                        	
2.Long Noncoding RNA Cytoskeleton Regulator RNA Suppresses Apoptosis in Hepatoma Cells by Modulating the miR-125a-5p/ HS1-Associated Protein X-1 Axis to Induce Caspase-9 Inactivation
Zhen-Yu WU ; Yumin WANG ; Hao HU ; Xiang-Nan AI ; Qiang ZHANG ; Yu-Gang QIN
Gut and Liver 2023;17(6):916-925
		                        		
		                        			 Background/Aims:
		                        			The involvement of long noncoding RNAs in the carcinogenesis of hepatocellular carcinoma (HCC) has been well documented by substantial evidence. However, whether cytoskeleton regulator RNA (CYTOR) could affect the progression of HCC remains unclear. 
		                        		
		                        			Methods:
		                        			The relative expression of CYTOR, miR-125a-5p and HS1-associated protein X-1 (HAX-1) mRNA in HCC cells were determined via quantitative real-time polymerase chain reaction. The viability of treated HCC cells was measured by Cell Counting Kit-8 assay. Cell apoptosis was estimated by flow cytometry analysis, assessment of caspase-9 activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, and Western blot of apoptosisrelated proteins. The interplay between CYTOR or HAX-1 and miR-125a-5p was validated by dual-luciferase reporter assay. 
		                        		
		                        			Results:
		                        			CYTOR was upregulated and miR-125a-5p was downregulated in HCC cells. CYTOR silencing inhibited cell proliferation and promoted cell apoptosis in HepG2 and SMMC-7721 cells.miR-125a-5p was sponged and negatively regulated by CYTOR, and HAX-1 was directly targeted and negatively modulated by miR-125a-5p. Overexpression of miR-125a-5p enhanced the repressive effects of CYTOR knockdown on HCC cells, and knockdown of HAX-1 enhanced the inhibitory effects of miR-125a-5p mimics on HCC cells. 
		                        		
		                        			Conclusions
		                        			CYTOR silencing facilitates HCC cell apoptosis in vitro via the miR-125a-5p/HAX-1 axis. 
		                        		
		                        		
		                        		
		                        	
3.Value of cardiac MRI in evaluation of left atrial function in the postoperative tetralogy of Fallot and pulmonary stenosis patients
Yanyan MA ; Rongzhen OUYANG ; Liwei HU ; Aimin SUN ; Qian WANG ; Chen GUO ; Yumin ZHONG
Chinese Journal of Radiology 2023;57(4):404-409
		                        		
		                        			
		                        			Objective:To explore the value of cardiac MRI (CMRI) in evaluating left atrial function in patients with postoperative tetralogy of Fallot (rTOF) and postoperative pulmonary stenosis (rPS).Methods:Totally 67 pediatric patients (49 with rTOF, 18 with rPS) with preserved left ventricular ejection fraction (EF) were recruited between January 2019 and October 2021 in Shanghai Children′s Medical Center, School of Medicine, Shanghai Jiao Tong University. Thirty-three healthy volunteers, matched in gender and age, were included as controls from July 2017 to August 2018. Left atrial EF, strain and strain rate of three phases (reservoir, conduit and pump), left atrial volume (maximum volume index, minimum volume index and pre-atrial contraction volume index) were measured with corresponding cardiac function analysis software. Then, the differences in these parameters were analyzed between the three groups by ANOVA or Kruskal-Wallis test with post hoc comparison and Bonferroni correction.Results:Compared with controls, patients with rTOF had lower reservoir function parameters (EF, strain and strain rate), conduit EF, conduit strain, and left atrial maximum volume index ( P<0.05), but higher pump EF ( P<0.05). In patients with rPS, only the reservoir strain rate decreased compared with controls ( P<0.05), and the remaining data showed no significant difference ( P>0.05). The reservoir and conduit EF and strain in patients with rPS were higher than those in patients with rTOF ( P<0.05). Conclusions:In patients with rTOF and rPS, left atrial function has changed despite the preservation of left ventricular EF, which may be an early marker of left ventricular diastolic dysfunction. In children with rTOF, left atrial reservoir and conduit functions decreased while the pump function increased. The reservoir and pump functions in rPS were better than those in rTOF. In addition, CMRI can detect left atrial dysfunction early before it enlarged.
		                        		
		                        		
		                        		
		                        	
4.Clinical characteristics and prognosis of febrile convulsions in children during the epidemic period of novel coronavirus Omicron variant
Lei WU ; Jie JIANG ; Yumin HU ; Xin WANG ; Hanjie YANG ; Jiayun SHI
Journal of Chinese Physician 2023;25(12):1806-1810
		                        		
		                        			
		                        			Objective:To evaluate the clinical characteristics and prognosis of febrile convulsions (FS) in children during the epidemic period of novel coronavirus Omicron variant.Methods:A retrospective analysis was conducted on the clinical data of pediatric patients diagnosed with FS at Changsha Central Hospital Affiliated to University of South China from February 1, 2022 to January 31, 2023. The clinical characteristics and prognosis of FS patients caused by Omicron variant infection (observation group) were compared with those caused by non Omicron variant infection (control group).Results:A total of 131 cases in the observation group and 341 cases in the control group; The proportion of children aged 12-36 months in the observation group was lower than that in the control group ( P<0.05), and the proportion of children aged ≥60 months was higher than that in the control group ( P<0.05). Most of the FS in the observation group occurred within 24 hours of fever (128/131, 97.7%), with a statistically significant difference compared to the control group ( P<0.05), and most of them were generalized tonic clonic seizures (127/131, 96.9%), with only one seizure during the course of the disease (114/131, 87.0%), consistent with the characteristics of simple FS. The main clinical symptoms of FS patients in the observation group were upper respiratory tract infections (108/131, 82.5%), which were significantly higher than those in the control group (164/341, 48.1%), while the incidence of lower respiratory tract infections was lower than that in the control group ( P<0.05). 369 pediatric patients were followed up by phone or outpatient visits, with 98 cases in the observation group and 2 cases experiencing recurrence. There was no recurrence in the group aged ≥60 months; A total of 271 cases were followed up in the control group, with 9 cases experiencing recurrence. Conclusions:The number of children with FS caused by novel coronavirus Omicron variant has increased sharply, and the proportion of late onset FS patients has increased significantly. Most of them are upper respiratory tract infections. Convulsions usually occur within 24 hours of fever, and the prognosis is good.
		                        		
		                        		
		                        		
		                        	
5.A prediction model based on contrast-enhanced MRI radiomics and clinical features for early recurrence of hepatocellular carcinoma after radical resection
Yang GAO ; Chuanqiang LAN ; Weichuan YE ; Yumin HU ; Jianjian XING ; Yongjin ZHOU ; Jingle FEI ; Jiansong JI
Chinese Journal of Hepatobiliary Surgery 2022;28(11):817-821
		                        		
		                        			
		                        			Objective:To develop a prediction model based on imaging features by contrast-enhanced MRI radiomics combined with clinical features for early recurrence of hepatocellular carcinoma (HCC) after radical resection.Methods:A retrospective study was carried out on 109 HCC patients who underwent radical resection at the Fifth Affiliated Hospital of Wenzhou Medical University from January 2015 to December 2020. Of 109 patients enrolled in this study, there were 96 males and 13 females, aged (58.3±10.7) years. Based on whether there was recurrence within 12 months after operation, the patients were divided into the early recurrence group ( n=31) and the control group ( n=78). These 109 patients were then randomly divided into the validation set ( n=23) and the training set ( n=86) at a ratio of 1∶4. Based on preoperative multi-phase contrast-enhanced MRI scanning, the tumor lesions were delineated on the Radcloud platform, and 1 409 quantitative radiomic features were extracted. Dimension reduction and screening of these features were carried out using variance threshold, SelectKBest and LASSO. Combined with clinical features (alpha fetoprotein, tumor size), several prediction model were established through machine learning. The predictive efficiencies of these models were evaluated using the area under the receiver operating characteristic (ROC) curve, accuracy rate, recall rate and balanced F score. Results:The proportions of irregular tumor shape and unclear tumor boundary, as well as maximum tumor diameter in the early recurrence group were significantly higher than that in the control group, but the proportion of pseudocapsule was significantly lower than that in the control group (all P<0.05). A total of 465 features were screened from the 1 409 features using the variance threshold method, followed by 38 features were screened using the method of SelectKBest. Finally 7 optimal radiomic features were screened based on the LASSO method. When combined with clinical features, 5 prediction models were established through machine learning. These models were support vector machine, Gaussian naive bayes, logistic regression, Multinomial naive bayes and K-nearest neighbor (KNN), respectively. Among these 5 models, the prediction efficiency of the KNN model was relatively highest, with the area under the ROC curve, accuracy rate, recall rate and balanced F score being 0.90, 0.98, 0.74 and 0.84 in the training set, and 0.76, 0.92, 0.75 and 0.83 in the verification set, respectively. Thus, the KNN model was selected as the best prediction model in this study. Conclusion:The prediction model of KNN was developed for early recurrence of HCC after radical resection based on preoperative contrast-enhanced MRI radiomics combined with clinical features.
		                        		
		                        		
		                        		
		                        	
6.Research progress on clinical features, diagnosis and treatment of late-onset systemic lupus erythematosus
Chinese Journal of Geriatrics 2022;41(8):986-991
		                        		
		                        			
		                        			Systemic lupus erythematosus(SLE)is an autoimmune disease with unknown etiology and pathogenesis, and is characterized by multiple organ involvement and the production of autoantibodies.Late-onset SLE means that clinical symptoms first occur after 50 years of age, often without typical skin lesions and implicating fewer target organs.It exhibits low disease activity, a high degree of cumulative damage, high rates of comorbidity and mortality, and abnormal immunological profiles, which make its diagnosis difficult.Due to the physiological state and disease characteristics in the elderly, the treatment is slightly different from that for SLE.This article reviews the clinical features, diagnosis and treatment of late-onset SLE to provide a basis for accurate diagnosis and treatment.
		                        		
		                        		
		                        		
		                        	
7.Primary inflammatory myofibroblastic sarcoma of the bladder: a case report
Jiajun CHEN ; Yang GAO ; Yumin HU ; Jiafeng DING ; Zhengyun LIU ; Jiansong JI
Chinese Journal of Urology 2022;43(10):788-789
		                        		
		                        			
		                        			The incidence of inflammatory myofibroblastic sarcoma is low, and bladder origin is more rare. We reported a 58-year-old patient with painless gross hematuria for one week. Total abdominal CT examination showed soft tissue mass in the anterior wall of the bladder, which was considered as bladder cancer, and bladder tumor resection was performed. Postoperative pathology showed inflammatory myofibroblastic sarcoma. Therefore, radical cystectomy was performed because of the high degree of malignancy. There was no recurrence during 3 years follow-up.
		                        		
		                        		
		                        		
		                        	
8.Feasibility of Three-Dimensional Balanced Steady-State Free Precession Cine Magnetic Resonance Imaging Combined with an Image Denoising Technique to Evaluate Cardiac Function in Children with Repaired Tetralogy of Fallot
YaFeng PENG ; XinYu SU ; LiWei HU ; Qian WANG ; RongZhen OUYANG ; AiMin SUN ; Chen GUO ; XiaoFen YAO ; Yong ZHANG ; LiJia WANG ; YuMin ZHONG
Korean Journal of Radiology 2021;22(9):1525-1536
		                        		
		                        			Objective:
		                        			To investigate the feasibility of cine three-dimensional (3D) balanced steady-state free precession (b-SSFP) imaging combined with a non-local means (NLM) algorithm for image denoising in evaluating cardiac function in children with repaired tetralogy of Fallot (rTOF). 
		                        		
		                        			Materials and Methods:
		                        			Thirty-five patients with rTOF (mean age, 12 years; range, 7–18 years) were enrolled to undergo cardiac cine image acquisition, including two-dimensional (2D) b-SSFP, 3D b-SSFP, and 3D b-SSFP combined with NLM. End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) of the two ventricles were measured and indexed by body surface index. Acquisition time and image quality were recorded and compared among the three imaging sequences. 
		                        		
		                        			Results:
		                        			3D b-SSFP with denoising vs. 2D b-SSFP had high correlation coefficients for EDV, ESV, SV, and EF of the left (0.959– 0.991; p < 0.001) as well as right (0.755–0.965; p < 0.001) ventricular metrics. The image acquisition time ± standard deviation (SD) was 25.1 ± 2.4 seconds for 3D b-SSFP compared with 277.6 ± 0.7 seconds for 2D b-SSFP, indicating a significantly shorter time with the 3D than the 2D sequence (p < 0.001). Image quality score was better with 3D b-SSFP combined with denoising than with 3D b-SSFP (mean ± SD, 3.8 ± 0.6 vs. 3.5 ± 0.6; p = 0.005). Signal-to-noise ratios for blood and myocardium as well as contrast between blood and myocardium were higher for 3D b-SSFP combined with denoising than for 3D b-SSFP (p < 0.05 for all but septal myocardium). 
		                        		
		                        			Conclusion
		                        			The 3D b-SSFP sequence can significantly reduce acquisition time compared to the 2D b-SSFP sequence for cine imaging in the evaluation of ventricular function in children with rTOF, and its quality can be further improved by combining it with an NLM denoising method.
		                        		
		                        		
		                        		
		                        	
9.Feasibility of Three-Dimensional Balanced Steady-State Free Precession Cine Magnetic Resonance Imaging Combined with an Image Denoising Technique to Evaluate Cardiac Function in Children with Repaired Tetralogy of Fallot
YaFeng PENG ; XinYu SU ; LiWei HU ; Qian WANG ; RongZhen OUYANG ; AiMin SUN ; Chen GUO ; XiaoFen YAO ; Yong ZHANG ; LiJia WANG ; YuMin ZHONG
Korean Journal of Radiology 2021;22(9):1525-1536
		                        		
		                        			Objective:
		                        			To investigate the feasibility of cine three-dimensional (3D) balanced steady-state free precession (b-SSFP) imaging combined with a non-local means (NLM) algorithm for image denoising in evaluating cardiac function in children with repaired tetralogy of Fallot (rTOF). 
		                        		
		                        			Materials and Methods:
		                        			Thirty-five patients with rTOF (mean age, 12 years; range, 7–18 years) were enrolled to undergo cardiac cine image acquisition, including two-dimensional (2D) b-SSFP, 3D b-SSFP, and 3D b-SSFP combined with NLM. End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) of the two ventricles were measured and indexed by body surface index. Acquisition time and image quality were recorded and compared among the three imaging sequences. 
		                        		
		                        			Results:
		                        			3D b-SSFP with denoising vs. 2D b-SSFP had high correlation coefficients for EDV, ESV, SV, and EF of the left (0.959– 0.991; p < 0.001) as well as right (0.755–0.965; p < 0.001) ventricular metrics. The image acquisition time ± standard deviation (SD) was 25.1 ± 2.4 seconds for 3D b-SSFP compared with 277.6 ± 0.7 seconds for 2D b-SSFP, indicating a significantly shorter time with the 3D than the 2D sequence (p < 0.001). Image quality score was better with 3D b-SSFP combined with denoising than with 3D b-SSFP (mean ± SD, 3.8 ± 0.6 vs. 3.5 ± 0.6; p = 0.005). Signal-to-noise ratios for blood and myocardium as well as contrast between blood and myocardium were higher for 3D b-SSFP combined with denoising than for 3D b-SSFP (p < 0.05 for all but septal myocardium). 
		                        		
		                        			Conclusion
		                        			The 3D b-SSFP sequence can significantly reduce acquisition time compared to the 2D b-SSFP sequence for cine imaging in the evaluation of ventricular function in children with rTOF, and its quality can be further improved by combining it with an NLM denoising method.
		                        		
		                        		
		                        		
		                        	
10.Application of three dimensional balanced steady state free precession cine MRI in evaluation of cardiac function in children with repaired tetralogy of Fallot
Yafeng PENG ; Liwei HU ; Aimin SUN ; Qian WANG ; Rongzhen OUYANG ; Chen GUO ; Xiaofen YAO ; Yumin ZHONG
Chinese Journal of Radiology 2020;54(7):649-654
		                        		
		                        			
		                        			Objective:To evaluate the feasibility of cardiac MRI three dimensional (3D) balanced steady state free precession (b-SSFP) cine imaging in evaluating cardiac function in children with repaired tetralogy of Fallot (TOF).Methods:Thirty children with repaired TOF underwent cardiac MRI examination at Shanghai Children′s Medical Cent er Affiliated to Shanghai Jiao Tong University School of Medicine, were retrospectively collected from April 2018 to October 2019. From June 2017 to August 2018, 10 healthy children were enrolled. Cardiac images of subjects were obtained using both two dimensional (2D) b-SSFP and 3D b-SSFP cardiac cine MRI and the total acquisition time was recorded. The image quality was scored using a 5-point scale, with a score≥3 as diagnostic image quality. The left and right ventricular end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), cardiac output (CO), and cardiac index (CI) were measured. The left and right ventricle parameters were compared using paired ttest or Wilcoxon test. The Pearson correlation or Spearman correlation analysis were used to evluate the correlation between the parameters measured with the 2 methods. Results:The acquisition time of 2D b-SSFP images was (426.5±13.0) s, and the total time of 3D b-SSFP images was (24.7±2.5) s. The 2D b-SSFP image quality score was better than 3D b-SSFP, and the differences were statistically significant (TOF patients: Z=-3.879, P<0.001; volunteers: Z=-2.646, P=0.003). All 2D and 3D b-SSFP image quality scores were ≥ 3 points, which can be used for clinical diagnosis. There were no statistically significant differences in cardiac function parameters between two series measurements in both TOF patients and volunteers ( P>0.05). For TOF patients, the left ventricular EDV, ESV, SV, EF, CO and right ventricular EDV, ESV, and SV showed highly positive correlation ( r>0.8, P<0.05). For volunteers, the left ventricular EDV, ESV, SV and right ventricular EDV and SV showed highly positive correlation ( r>0.8, P<0.05). Conclusion:Compared with the 2D b-SSFP sequence, 3D b-SSFP sequence with fairy good image quality can meet the diagnostic requirement and can accurately measure the cardiac function with shorter acquisition time. The 3D b-SSFP has a good application prospect in pediatric cardiac MRI.
		                        		
		                        		
		                        		
		                        	
            
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