1.Structural and epitope characterization of HIV-1 V1V2 highly effective neutralizing antibodies based on AlphaFold 3
Junjie ZHANG ; Qianying WANG ; Ying LIU ; Shuhui WANG ; Li REN ; Shuo WANG ; Yutao SHI ; Yuhua RUAN ; Xiaojing LIU ; Xinran DU ; Yanling HAO ; Dan LI
Chinese Journal of Experimental and Clinical Virology 2025;39(5):548-555
Objective:To screen broadly neutralizing antibodies in human immunodeficiency virus-1(HIV-1)chronically infected individuals and characterize their molecular features and to provide new strategies for rational vaccine development and antibody-based therapeutics.Methods:A total of 34 treatment-na?ve individuals with chronic HIV-1 infection were enrolled. Plasma antibody binding levels were measured against two HIV-1 envelope proteins. Single antigen-specific memory B cells were sorted from high-binding samples,and antibody variable region genes were amplified by PCR for paired expression. The monoclonal antibodies were evaluated for neutralizing activity using pseudovirus assays,and their structural features were analyzed by integrating AlphaFold 3 prediction with Discovery Studio molecular docking.Results:Plasma samples showed strong binding to DU422-GP140 and BG505-GP140. Eight monoclonal antibodies were isolated from two donors. Among them,antibodies 0919-A4,0919-A9 and 0808-A2 could cross-react with GP140 from HIV-1 subtypes AE,BC and B. The monoclonal antibody 0919-A9 demonstrated potent neutralizing activity against SF162(Tier 1)and CH181(Tier 2)pseudoviruses,with somatic hypermutation rates of 13.27%(heavy chain)and 15.58%(light chain). Structural modeling revealed its specific targeting of the V1V2 region on GP120.Conclusion:The isolated antibody 0919-A9 effectively neutralizes Tier 2 pseudoviruses. Its high somatic mutation frequency and V1V2-targeting property underlie its neutralizing activity,providing both a promising candidate and mechanistic insights for HIV vaccine development and antibody-based therapeutic strategies.
2.USP20 as a super-enhancer-regulated gene drives T-ALL progression via HIF1A deubiquitination.
Ling XU ; Zimu ZHANG ; Juanjuan YU ; Tongting JI ; Jia CHENG ; Xiaodong FEI ; Xinran CHU ; Yanfang TAO ; Yan XU ; Pengju YANG ; Wenyuan LIU ; Gen LI ; Yongping ZHANG ; Yan LI ; Fenli ZHANG ; Ying YANG ; Bi ZHOU ; Yumeng WU ; Zhongling WEI ; Yanling CHEN ; Jianwei WANG ; Di WU ; Xiaolu LI ; Yang YANG ; Guanghui QIAN ; Hongli YIN ; Shuiyan WU ; Shuqi ZHANG ; Dan LIU ; Jun-Jie FAN ; Lei SHI ; Xiaodong WANG ; Shaoyan HU ; Jun LU ; Jian PAN
Acta Pharmaceutica Sinica B 2025;15(9):4751-4771
T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.
3.Diagnostic value of MS score in macrophage activation syndrome associated with systemic juvenile idiopathic arthritis
Lingling GENG ; Yue PENG ; Duomei SHI ; Li WANG ; Xianyan TANG ; Xinran WEN ; Wenhua ZHANG ; Xiaoqing LI
International Journal of Pediatrics 2025;52(7):476-480
Objective:To explore the diagnostic value of the macrophage activation syndrome/systemic juvenile idiopathic arthritis(MS)score in macrophage activation syndrome(MAS)associated with systemic juvenile idiopathic arthritis(sJIA),and to provide a reference for clinical work.Methods:This study was a retrospective case-control analysis,conducted on the patients initially diagnosed as sJIA-associated with MAS and admitted into the Department of Rheumatology and Immunology of Children's Hospital Affiliated to Xi 'an Jiaotong University from July 1st,2016 to June 30th,2023. All of the patients met the diagnostic criteria for patients with MAS associated with sJIA according to the 2016 European Alliance of Associations for Rheumatology(EULAR)/American College of Rheumatology(ACR)/Pediatric Rheumatology International Trials Organization(PRINTO)standards. The basic information at baseline,clinical manifestations,and auxiliary examination results were collected. The MS score was applied to re-evaluate the children diagnosed as sJIA-associated with MAS. When the MS score ≥-2.1,the possibility of sJIA with MAS was high. Thirty cases of sJIA without MAS were randomly selected as the control group.Results:There were 28 cases in the MAS group,including 13 males(46.43%)and 15 females(53.57%),with an average age of(7.51±4.01)years. Compared with the control group,the MAS group were significantly more likely to have high fever( χ2=8.539, P=0.003),hepatomegaly( χ2=11.621, P<0.001),splenomegaly( χ2=11.710, P<0.001)and neurological involvement( χ2=27.619, P<0.001),with the differences being statistically significant. Meanwhile,there were statistically significant differences between the two groups in terms of white blood cell count( Z=-4.001, P<0.001),neutrophil count( Z=-3.659, P<0.001),platelet count( Z=-4.687, P<0.001),albumin level( Z=-4.018, P<0.001),alanine aminotransferase( Z=-3.846, P<0.001),aspartate aminotransferase( Z=-5.932, P<0.001),lactate dehydrogenase( Z=-6.150, P<0.001),triglycerides( Z=-5.874, P<0.001),fibrinogen( Z=-5.808, P<0.001),ferritin( Z=-5.280, P<0.001),erythrocyte sedimentation rate( Z=-3.971, P<0.001),ferritin/erythrocyte sedimentation rate( Z=-5.433, P<0.001),reduction of two-line cells in blood( χ2=11.408, P<0.001)and the presence of hemophagocytosis in bone marrow smears( χ2=28.260, P<0.001). Moreover,there was a statistically significant difference in MS scores between the two groups( Z=-6.148, P<0.001),with higher MS scores in the MAS group. Nevertheless,this study showed the median MS scores of both groups ≥-2.1. Conclusion:The MS score was significant to a certain degree as reference for the diagnosis of MAS,and this study showed that the MS score in the MAS group was significantly higher than the control group. However,the median MS scores in both groups were no less than -2.1. This might be related to the influence of factors during the assessment,which made it necessary to optimize the cutoff values of the MS score. Therefore,prospective studies should be carried out on the role of MS score in early identification of MAS.
4.Changes in the body shape and ergonomic compatibility for functional dimensions of desks and chairs for students in Harbin during 2010-2024
Chinese Journal of School Health 2025;46(3):315-320
Objective:
To analyze the change trends in the body shape indicators and proportions of students in Harbin from 2010 to 2024, and to investigate ergonomic compatibility of functional dimensions of school desks and chairs with current student shape indicators, so as to provide a reference for revising furniture standards of desks and chairs.
Methods:
Between September and November of both 2010 and 2024, a combination of convenience sampling and stratified cluster random sampling was conducted across three districts in Harbin, yielding samples of 6 590 and 6 252 students, respectively. Anthropometric shape indicators cluding height, sitting height, crus length, and thigh length-and their proportional changes were compared over the 15-year period. The 2024 data were compared with current standard functional dimensions of school furniture. The statistical analysis incorporated t-test and Mann-Whitney U- test.
Results:
From 2010 to 2024, average height increased by 1.8 cm for boys and 1.5 cm for girls; sitting height increased by 1.5 cm for both genders; crus length increased by 0.3 cm for boys and 0.4 cm for girls; and thigh length increased by 0.5 cm for both genders. The ratios of sitting height to height, and sitting height to leg length increased by less than 0.1 . The difference between desk chair height and 1/3 sitting height ranged from 0.4-0.8 cm. Among students matched with size 0 desks and chairs, 22.0% had a desk to chair height difference less than 0, indicating that the desk to chair height difference might be insufficient for taller students. The differences between seat height and fibular height ranged from -1.4 to 1.1 cm; and the differences between seat depth and buttock popliteal length ranged from -9.8 to 3.4 cm. Among obese students, the differences between seat width and 1/2 hip circumference ranged from -20.5 to -8.7 cm, while it ranged from -12.2 to -3.8 cm among non obese students.
Conclusion
Current furniture standards basically satisfy hygienic requirements; however, in the case of exceptionally tall and obese students, ergonomic accommodations such as adaptive seating allocation or personalized adjustments are recommended to meet hygienic requirements.
5.Association Between Vitamin D Status and Insulin Resistance in Adolescents: A Cross-sectional Observational Study
Xiaoyuan GUO ; Yutong WANG ; Zhibo ZHOU ; Shi CHEN ; Mei ZHANG ; Bo BAN ; Ping LI ; Xinran ZHANG ; Qiuping ZHANG ; Kai YANG ; Hongbo YANG ; Hanze DU ; Hui PAN
Medical Journal of Peking Union Medical College Hospital 2025;16(3):577-583
To investigate the correlation between vitamin D nutritional status and insulin resistance in pubertal adolescents. This cross-sectional observational study employed convenience sampling to recruit 2021-grade(8th grade) students from Jining No.7 Middle School in Shandong Province on June 5, 2023. Data collection included questionnaires, physical examinations, and imaging assessments to obtain general information, secondary sexual characteristics development, and bone age. Venous blood samples were collected to measure fasting blood glucose(FBG), fasting insulin(FINS), homeostasis model assessment of insulin resistance(HOMA-IR), and 25-hydroxyvitamin D[25(OH)D] levels. Spearman correlation analysis and multivariate linear regression models were used to examine the associations between serum vitamin D levels and FBG, FINS, and HOMA-IR. The study included 168 pubertal adolescents[69 females(41.1%), 99 males(58.9%); mean age(13.27±0.46) years]. All participants had entered puberty based on sexual development assessment. Vitamin D deficiency was observed in 41 participants(24.4%), insufficiency in 109(64.9%), and sufficiency in 18(10.7%). The median HOMA-IR was 3.49(2.57, 5.14).Significant differences were found across vitamin D status groups for HOMA-IR [4.45(2.54, 6.62) Vitamin D deficiency/insufficiency is prevalent among pubertal adolescents, and serum vitamin D levels show a significant inverse association with insulin resistance. These findings suggest the potential importance of vitamin D status in metabolic health during puberty.
6.Body Composition Profiles and Associated Factors in Adolescents UndergoingLong-term Regular Exercise
Yutong WANG ; Xiaoyuan GUO ; Hanze DU ; Hui PAN ; Wei WANG ; Mei ZHANG ; Bo BAN ; Ping LI ; Xinran ZHANG ; Qiuping ZHANG ; Hongshuang SUN ; Rong LI ; Shi CHEN
Medical Journal of Peking Union Medical College Hospital 2025;16(3):591-597
To investigate body composition and associated factors in adolescents undergoing long-term regular sports training. This prospective longitudinal cohort study employed convenience sampling to recruit adolescents receiving structured athletic training at Jining Sports Training Center in June 2023. Baseline measurements included height, weight, body mass index (BMI), blood pressure, heart rate, waist circumference, and hip circumference. Questionnaires assessed sleep duration, screen time, and household income. Follow-up measurements in June 2024 repeated these assessments while adding bioelectrical impedance analysis for body composition (lean mass, skeletal muscle mass, fat mass, and body fat percentage). Linear regression models examined associations between training type (direct-contact vs. non-contact sports) and follow-up body fat percentage, BMI, and waist circumference as dependent variables, adjusting for covariates. The study included 110 adolescents (39 female, 71 male) with median age 13.21 years (IQR: 12.46-14.33). Participants comprised 65 direct-contact and 45 non-contact athletes. Baseline prevalence rates were 27.27% for overweight/obesity, 24.55% for elevated waist circumference, and 16.36% for elevated blood pressure. At follow-up, corresponding rates were 24.55%, 26.36%, and 13.64% respectively. The elevated blood pressure subgroup showed significantly higher waist circumference ( Despite regular athletic training, substantial proportions of adolescents exhibited overweight/obesity, abdominal obesity, and elevated blood pressure, warranting clinical attention. Training modality appears to influence body composition changes, with direct-contact sports associated with more favorable adiposity-related outcomes.
7.Morphological and hemodynamic parameters of CT angiography for predicting recurrence of intracranial aneurysms after endovascular embolization
Xinran WANG ; Bin HU ; Zhao SHI ; Longjiang ZHANG
Chinese Journal of Medical Imaging Technology 2025;41(1):9-14
Objective To investigate the value of morphological and hemodynamic parameters of CT angiography(CTA)for predicting recurrence of intracranial aneurysms(IA)after endovascular embolization.Methods Totally 205 patients with ruptured IA who underwent endovascular embolization were retrospectively collected and divided into recurrence group(n=35)and non-recurrence group(n=170)according to follow-up results after embolization.The morphological and hemodynamic parameters of IA in CTA before treatment were compared between groups.Variance inflation factor(VIF)was used to explore whether there was collinearity between morphological and hemodynamic parameters,and those without collinearity were included in univariate and multivariate logistic regression analysis to screen predictors of recurrence of IA after endovascular embolization.Two prediction models were constructed based on morphological parameters(model 1)and combination with hemodynamic parameters(model 2).Receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to evaluate the predictive efficacy of models.Results The maximum diameter,aneurysm neck width,maximum height,maximum vertical height and size ratio(SR)of IA in recurrence group were all higher than those in non-recurrence group(all P<0.05),while gradient oscillatory number(GON)in recurrence group was lower than that in non-recurrence group(P<0.05).The neck width,SR,pressure at IA neck plane,intra-aneurysm time-averaged wall shear stress(TAWSS),oscillatory shear index(OSI)and GON had no significant collinearity(all VIF<10),among which the neck width,SR and TAWSS were all independent predictors(all P<0.05).AUC of model 1 and model 2 for predicting recurrence of IA after endovascular embolization was 0.668 and 0.723,respectively,which of model 2 was higher than which of model 1(integrated discrimination improvement index was 0.055,P=0.025).Conclusion CTA morphological parameters combined with hemodynamic parameters of IA could be used to predict its recurrence after endovascular embolization.
8.Establishing a risk prediction model for the onset of female stress urinary incontinence based on machine learning
Xinran SHI ; Zhen PANG ; Ting QIAO ; Jingjing LI ; Qinzhang WANG
Journal of Modern Urology 2025;30(3):196-206
Objective: To construct prediction models of female stress urinary incontinence (SUI), and evaluate the efficacy of each model, so as to provide reference for the early diagnosis of SUI. Methods: Female SUI patients treated in our hospital during Oct. 2019 and Oct. 2023 and healthy women undergoing physical examination during the same period were involved. Women 42 days after delivery were included in the postpartum group (n=611), and perimenopausal and postmenopausal women were included in the non-postpartum group (n=409). The number of random seeds was set and the participants were divided into the training and verification sets in a ratio of 7∶3. Relevant clinical data were collected, and meaningful variables were screened using single factor and Lasso regression, which were then incorporated into the K-nearest neighbor method (KNN), support vector machine (SVM),decision tree (DT) and random forest (RF) algorithms. The sensitivity, specificity, accuracy and area under the receiver operating characteristic curve (AUC) of the models were calculated to screen out the optimal model. Results: There were 352 SUI patients (57.6%) in the postpartum group. According to single factor and Lasso regression, significant variables included age, body mass index (BMI), maximum rapid muscle stage, parity, bladder neck mobility (BND), urethral rotation angle (URA), lateral perineal incision, past incontinence, and constipation. In the verification set, the AUC of KNN,SVM,DT and RF models were 0.881,0.878,0.750 and 0.905,respectively; the AUC, accuracy, F1 index and Kappa value of RF model were the largest. In the non-postpartum group, there were 260 SUI patients, accounting for 63.6%. The significant variables were age,BMI, maximum value and recovery time of fast muscle stage, mean value of slow muscle stage, post-resting stage variability, vaginal delivery, past incontinence, and constipation. In the verification set, the AUC of KNN,SVM,DT and RF models were 0.819,0.805,0.603 and 0.830, respectively; the AUC, accuracy, Kappa value of the RF model were the largest. Conclusion: This study successfully established 4 prediction models for the incidence of SUI in women at 42 days postpartum, perimenopausal and postmenopausal women based on machine learning. Among them, the model adopting the RF algorithm had the best prediction efficiency.
9.COVID-19 outcomes in patients with pre-existing interstitial lung disease: A national multi-center registry-based study in China.
Xinran ZHANG ; Bingbing XIE ; Huilan ZHANG ; Yanhong REN ; Qun LUO ; Junling YANG ; Jiuwu BAI ; Xiu GU ; Hong JIN ; Jing GENG ; Shiyao WANG ; Xuan HE ; Dingyuan JIANG ; Jiarui HE ; Sa LUO ; Shi SHU ; Huaping DAI
Chinese Medical Journal 2025;138(9):1126-1128
10.Analysis of single-center clinical data of juvenile dermatomyositis complicated with interstitial lung disease
Lingling GENG ; Yue PENG ; Li WANG ; Xiuhong XUE ; Xinran WEN ; Duomei SHI ; Xiaoqing LI
Chinese Pediatric Emergency Medicine 2025;32(10):764-768
Objective:To summarize the clinical data of single-center juvenile dermatomyositis(JDM)complicated with interstitial lung disease(ILD),and provide experience for pediatricians.Methods:Data of 61 children with JDM who were admitted to Children's Hospital affiliated to Xi'an Jiaotong University from January 2016 to May 2023 were collected. General data,clinical symptoms,chest high-resolution CT,laboratory examination and myositis antibody spectrum of the children were recorded.Results:Among the 61 children with JDM,there were 30 cases(13 males and 17 females)without ILD. The age of onset was 5.96(3.50,8.92)years and the course of disease was(11.79±20.00)months. There were 31 cases with ILD(14 males and 17 females),the age of onset was 7.42(4.50,10.08)years,and the duration of ILD was(5.47±8.09)months. There was statistical difference in the course of disease between the two groups( P<0.05),but no statistical difference in gender and age between the two groups( P>0.05). Among 61 children with JDM,there were statistical differences in fever between the two groups( P<0.05),but no statistical differences in heliotrope discoloration,gottron’s papules,calcinosis and myasthenia between the two groups( P>0.05). AST and FER showed statistical difference between the two groups( P<0.05),while CK,LDH,CK-MB,ESR,C3 and C4 showed no statistical difference( P>0.05). All 61 cases of children were tested for myositis antibody spectrum,and there was statistical difference in anti-MDA5 antibody between the two groups( P<0.05),but no statistical difference in the rest( P>0.05). There were statistical differences between the two groups in the treatment of methotrexate,hydroxychloroquine and cyclophosphamide( P<0.05). A total of 11 cases(36.67%)in the without ILD group were treated with biologics(8 adalimumab,2 infliximab and 1 tofacitinib),and 23 cases(74.19%)in the ILD group were treated with biologics(11 adalimumab,9 tofaciib,2 infliximab and 1 tocilizumab). All 61 cases with JDM were followed up. Among the 30 children without ILD,1 case was lost to follow-up 2 months after treatment,and the rest were treated effectively without death. Among the 31 children with ILD,3 cases died of severe pulmonary infection with multidrug-resistant bacteria during treatment,of which 1 case was positive for anti-MDA5 antibody and 2 cases were negative for myositis specific antibody. Conclusion:JDM is more likely to be complicated with ILD,fever is more likely to occur in ILD group,and children with positive anti-MDA5 antibody are more likely to occur ILD. Biologic agents such as adalimumab and tofacitinib are effective in combination therapy. In the course of treatment,multi-drug resistant bacteria infection should be guarded against to reduce mortality.


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