1.DiPTAC: A degradation platform via directly targeting proteasome.
Yutong TU ; Qian YU ; Mengna LI ; Lixin GAO ; Jialuo MAO ; Jingkun MA ; Xiaowu DONG ; Jinxin CHE ; Chong ZHANG ; Linghui ZENG ; Huajian ZHU ; Jiaan SHAO ; Jingli HOU ; Liming HU ; Bingbing WAN ; Jia LI ; Yubo ZHOU ; Jiankang ZHANG
Acta Pharmaceutica Sinica B 2025;15(1):661-664
2.Associations of fundus vasculopathy with cerebral small vessel disease and cognitive impairment
Yutong HOU ; Lei YANG ; Shuna YANG ; Wei QIN ; Chunmei CUI ; Ying LI ; Wenli HU
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(5):552-556
Objective To investigate the correlation between the total CSVD burden and fundus vasculopathy,and evaluate significance of fundus vasculopathy for cognitive impairment in CSVD patients.Methods A total of 290 inpatients who taking physical examination in our department from May 2021 to August 2022 were consecutively recruited,and according to their score of CSVD,they were divided into group 0(129 cases),group 1(51 case),group 2(42 cases),group 3(44 cases),and group 4(24 cases).All the subjects underwent brain magnetic resonance imaging,fundus fluorescein angiography,and cognitive function assessment.The total CSVD burden and fundus vasculopathy were evaluated.The general clinical data,results of laboratory tests,fundus vascularization,and cognitive function were compared among the groups with different CSVD burden scores.Spearman correlation analysis and linear correlation analysis were used to explore the correlation between total CSVD burden score and fundus vascular disease.Results Significant differences were observed in terms of age,years of education,cerebral infarction/TIA,total cho-lesterol,LDL-C,creatinine,MoC A and MMSE scores,positive results of connectivity test,digit-symbol conversion test,Stroop colour-word interference test and verbal fluency test,values of CRAE,CRVE,AVR,Scheie grade,DWMH and PVWMH,enlarged perivascular space in the basal ganglia(BG-EPVS),lacunar infarct and cerebral microbleeds(CMB)in different CSVD total bur-den groups(P<0.05,P<0.01).Spearman correlation analysis showed that total CSVD burden was negatively correlated with CRAE and AVR(r=-0.655,P=0.000;r=-0.679,P=0.000),and positively with CRVE and Scheie grade(r=0.560,P=0.000;r=0.685,P=0.000).Multivari-ate linear analysis showed that the total CSVD burden after adjusting for relevant risk factors was significantly correlated with CRAE,CRVE,AVR and Scheie grades(P<0.01).Conclusion Fun-dus vasculopathy is strongly associated with increased total CSVD burden,and it can be regarded as a valid predictor of CSVD-related cognitive impairment.
3.Diagnostic value of serum serine protease Corin in patients with chronic renal failure complicated with heart failure
Pengfei ZHOU ; Shiyu LIU ; Wen FANG ; Ruihua CHEN ; Zihan ZHOU ; Xiaomei HOU ; Yutong YAN ; Yahui HU
Chinese Journal of Laboratory Medicine 2024;47(6):610-618
Objective:To investigate the diagnostic value of serum serine protease (Corin) in chronic renal failure (CRF) complicated with heart failure.Methods:A retrospective analysis was conducted on 120 patients, (64.05±13.89) years old, 77 male (64.17%), with chronic renal failure combined with heart failure admitted to Zhengzhou People′s Hospital from January 1, 2023, to December 31, 2023. The control group consisted of 87 patients, (60.59±8.78) years old, 54 male (62.07%), with simple chronic renal failure. Clinical information, laboratory test indicators and echocardiographic parameters were collected. Serum Corin concentration was measured using enzyme-linked immunosorbent assay (ELISA). The experimental group was divided into grade Ⅱ(31 cases), grade Ⅲ(47 cases) and grade Ⅳ(42 cases) according to the New York College of Cardiology heart function classification system. Serum Corin levels were compared between the experimental group and the control group and among different cardiac function grades. Spearman correlation analysis was performed to evaluate the relationship between serum Corin and brain natriuretic peptide (BNP), D-dimer. ROC analysis was conducted to assess the predictive value of serum Corin in CRF complicated with heart failure and cardiac function classification; Binary Logistic regression was used to construct a multi-index joint prediction model, the joint prediction probability was obtained, and ROC curve was drawn to compare the diagnostic value of serum Corin and BNP in CRF combined with heart failure and the diagnostic value of serum Corin combined with D-dimer and BNP in CRF combined with heart failure.Results:The serum Corin level[2 568.97±477.70 pg/ml vs. 1 727.81±480.60 pg/ml, t=12.47, P<0.001], BNP [700.00(256.00, 2 089.75) pg/ml compared with 88.00 (43.00, 230.00) pg/ml, Z=-9.00, P<0.001], D-dimer [1 150.00(643.00, 1 874.75)μg/L compared with 556.00 (301.00, 865.00)μg/L, Z=-6.57, P<0.001] in chronic renal failure complicated with heart failure group was higher than that in simple CRF group, and the difference was statistically significant. Among patients with CRF complicated with heart failure, serum Corin[2 231.74±311.39 pg/ml vs. 2 562.09±365.30 pg/ml vs. 2 825.57±536.83 pg/ml, F=74.33, P<0.001], BNP [234.00(168.00, 612.00) pg/ml compared with 514.00(260.00, 1 455.00) pg/ml compared with 2 200.00(640.50, 4 682.75) pg/ml, H=29.42, P<0.001], D-dimer [753.00(514.00, 1 280.00) μg/L compared with 1 187.00(590.00, 1 840.00) μg/L compared with 1 603.00(810.00, 3 313.25) μg/L, H=14.98, P<0.001] increased with the increase of cardiac function grade, and the difference was statistically significant. According to Spearman correlation analysis, serum Corin was positively correlated with BNP ( r=0.409) and D-dimer ( r=0.299), P<0.001. According to the ROC analysis, the AUC of serum Corin in the diagnosis of CRF complicated with heart failure and cardiac function grade Ⅱ, Ⅲ, Ⅳ were 0.890(95% CI 0.846-0.935), 0.807 (95% CI 0.728-0.885), 0.911 (95% CI 0.864-0.959), 0.927 (95% CI 0.882-0.972) respectively; the AUC of BNP in the diagnosis of CRF complicated with heart failure was 0.867 (95% CI 0.817-0.916), the AUC of serum Corin combined with D-dimer, BNP combined with D-dimer, serum Corin combined with D-dimer and BNP in the diagnosis of CRF complicated with heart failure were respectively 0.930 (95% CI 0.897-0.962), 0.892 (95% CI 0.847-0.936), 0.952 (95% CI 0.927-0.977). Conclusions:Serum Corin expression is elevated in patients with CRF complicated with heart failure, and the degree of elevation is related to cardiac function grade. Serum Corin has a good diagnostic value for CRF complicated with heart failure and its severity. Serum Corin is expected to become a new biomarker for diagnosis of CRF complicated with heart failure.
4.Correlation between sagittal curvature parameters and pain threshold for neck-shoulder muscles in degenerative cervical spondylosis
Yunxiao YANG ; Chenglan HUANG ; Yutong HOU ; Yuan YAO ; Yu ZHAO ; Yuanjing XU ; Zezheng YANG ; Jinwu WANG
Chinese Journal of Tissue Engineering Research 2024;28(24):3879-3884
BACKGROUND:Patients with degenerative cervical spondylosis often suffer from changed varicosity of the cervical spine,unbalanced neck-shoulder muscular strength,and descending power. OBJECTIVE:To probe into the correlation between sagittal curvature parameters and pain threshold for neck-shoulder muscles in degenerative cervical spondylosis. METHODS:Totally 50 patients with degenerative cervical spondylosis received treatment at the 3D Printed Outpatient Center of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from January 2022 to March 2023 were included in the study.After excluding the 10 patients of cervical lateral projection that failed to meet the measurement conditions,the cervical lateral projections were shot to measure the following iconography parameters:Borden value and C2-7 Cobb angle as well as pain thresholds on the midpoint of the superior trapezius muscle in bilateral bundles and at 1 cm beside the C5-6 interspike.The correlation between sagittal curvature parameters and pain threshold of neck-shoulder muscles in degenerative cervical spondylosis was analyzed. RESULTS AND CONCLUSION:(1)The Borden value of sagittal curvature showed a moderately positive correlation with the bundle pain threshold in the left upper trapezius muscle,the bundle pain threshold in the right upper trapezius muscle,and the pain threshold at the 1 cm of the left side beside the C5-6 interspike(r=0.498,P<0.01;r=0.448,P<0.05;r=0.405,P<0.05)and a weak positive correlation with the pain threshold at the 1 cm of the right side beside the C5-6 interspike(r=0.322,P<0.05).(2)The C2-7 Cobb angle showed a weak positive correlation with the left squared myalgia threshold(r=0.355,P<0.05),and there was no correlation with the pain threshold of the left trapezius muscle and the pain threshold at the 1 cm of both sides beside the C5-6 interspike.(3)There was a correlation between the pain threshold of the neck-shoulder muscles,and a high correlation between the pain threshold of the left and right muscles and the pain threshold within the left and right side muscles,indicating that the neck-shoulder muscles are consistent and may be related to the coordination of the neck-shoulder movements.
5.Correlation between lumbar spine and pelvic parameters in Lenke type 5 adolescent idiopathic scoliosis
Yutong HOU ; Chenglan HUANG ; Yunxiao YANG ; Ya LI ; Peiwu GUO ; Wenqiang YU ; Yu ZHAO ; Zanbo WANG ; Hong ZENG ; Zhenjiang MA ; Dezhi LU ; Jinwu WANG
Chinese Journal of Tissue Engineering Research 2024;28(36):5753-5758
BACKGROUND:The study of the lumbar spine and pelvis in patients with Lenke type 5 lordosis is limited to the coronal and sagittal planes,and the three-dimensional relationship between the scoliosis and the pelvis has not yet been clarified. OBJECTIVE:To analyze the effect of lumbar scoliosis on the pelvis in patients with Lenke type 5 lordosis and to study the correlation between the lumbar spine and the three-dimensional spatial position of the pelvis. METHODS:Imaging data of 60 patients with Lenke type 5 lordosis scoliosis admitted to the 3D Printing Reception Center of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from January 2019 to September 2023 were retrospectively analyzed,including Cobb angle,coronal pelvic tilt,lumbar lordosis,left and right pelvic hip width ratio(sacroiliac-anterior superior iliac spine),spinal rotation angle,pelvic tilt,sacral slope,pelvic incidence,coronal deformity angular ratio,sagittal deformity angular ratio,C7 plumb line-center sacral vertical line,apical vertebral translation,and coronal sacral inclination.The information was summarized as a database.SPSS 22.0 software was used to analyze the data related to the lumbar spine and pelvis of the patients with Lenke type 5 primary lumbar curvature adolescent idiopathic scoliosis using Spearman's correlation analysis and linear regression. RESULTS AND CONCLUSION:(1)Cobb angle was highly positively correlated with coronal deformity angular ratio,apical vertebral translation,and spinal rotation angle(r=0.91,r=0.841,r=0.736).(2)Coronal deformity angular ratio was highly positively correlated with apical vertebral translation(r=0.737),moderately positively correlated with C7 plumb line-center sacral vertical line(r=0.514),and moderately negatively correlated with sagittal deformity angular ratio(r=-0.595).(3)There was a high positive correlation between lumbar lordosis and sagittal deformity angular ratio(r=0.942)and a moderate negative correlation with coronal deformity angular ratio(r=-0.554).(4)There was a moderate positive correlation between Cobb angle with coronal pelvic tilt and coronal sacral inclination(r=0.522,r=0.534)and a moderate positive correlation between C7 plumb line-center sacral vertical line and coronal pelvic tilt(r=0.507).Apical vertebral translation with coronal pelvic tilt and coronal sacral inclination showed a moderate positive correlation(r=0.507,r=0.506).Lumbar lordosis with sacral slope and pelvic incidence showed a moderate positive correlation(r=0.512,r=0.538).Sagittal deformity angular ratio was moderately positively correlated with sacral slope and pelvic incidence(r=0.614,r=0.621).(5)Studies have found that the relative position of the lumbar spine and the pelvis is closely related in the horizontal,sagittal and coronal planes.When the lumbar spine affects scoliosis and is rotated,the relative position of the pelvis will also change to compensate,which indicates that while correcting scoliosis,the correction of the pelvis cannot be ignored.
6.Original Article Association between Exposure of Rare Earth Elements and Outcomes of In Vitro Fertilization-Embryo Transfer in Beijing
Wang YUTONG ; Li JING ; Xu SHIRONG ; Lin SHENGLI ; Hou ZHENCHEN ; Wang LINLIN ; Huang YALI ; Sun YUE ; Guo WEI ; Yan LAILAI ; Wang YING ; Tian CHAN
Biomedical and Environmental Sciences 2024;37(8):876-886
Objective The study aimed to investigate the impact of rare earth elements(REEs)exposure on pregnancy outcomes of in vitro fertilization-embryo transfer(IVF-ET)by analyzing samples from spouses. Methods A total of 141 couples were included.Blood and follicular fluid from the wives and semen plasma from the husbands,were analyzed for REEs using inductively coupled plasma mass spectrometry(ICP-MS).Spearman's correlation coefficients and the Mann-Whitney U test were used to assess correlations and compare REE concentrations among three types of samples,respectively.Logistic models were utilized to estimate the individual REE effect on IVF-ET outcomes,while BKMR and WQS models explored the mixture of REE interaction effects on IVF-ET outcomes. Results Higher La concentration in semen(median 0.089 ng/mL,P=0.03)was associated with a lower fertilization rate.However,this effect was not observed after artificial selection intervention through intracytoplasmic sperm injection(ICSI)(P=0.27).In semen,the REEs mixture did not exhibit any significant association with clinical pregnancy. Conclusion Our study revealed a potential association between high La exposure in semen and a decline in fertilization rate,but not clinical pregnancy rate.This is the first to report REEs concentrations in follicular fluid with La,Ce,Pr,and Nd found at significantly lower concentrations than in serum,suggesting that these four REEs may not accumulate in the female reproductive system.However,at the current exposure levels,mixed REEs exposure did not exhibit reproductive toxicity.
7.Comparison of human-induced pluripotent stem cell-derived macrophages with peripheral blood-derived macrophages using single-cell genomics
Yutong ZHANG ; Guojun HOU ; Nan SHEN
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(12):1477-1489
Objective·To explore the heterogeneity in single-cell genomics between human-induced pluripotent stem cell(iPSC)-derived macrophages(IPSDM)and human peripheral blood-derived macrophages(PBDM).Methods·iPSCs were differentiated into IPSDMs in vitro using a feeder-free and serum-free protocol.The expression of cluster of differentiation antigen 14(CD14)and monocyte-macrophage marker genes in IPSDMs was analyzed using flow cytometry and real-time reverse transcription quantitative polymerase chain reaction(RT-qPCR),respectively.Single-cell sequencing was then performed on IPSDMs.Simultaneously,the single-cell sequencing dataset GSE126085 was downloaded from the Gene Expression Omnibus database as a reference dataset for PBDMs.Sequencing data for both IPSDMs and PBDMs were processed and analyzed using the seurat package in R software,with PBDMs annotated using the singleR package.A reference dataset was constructed with highly variable genes from PBDMs,and the highly variable genes of IPSDMs were projected onto the PBDM dataset using the scmap package to infer IPSDMs cell identities based on variable gene similarity.IPSDMs were annotated using cell-type annotation tools and referenced against relevant studies.The expression distribution of macrophage marker genes was compared between IPSDMs and PBDMs.Differentially expressed genes(DEGs)between IPSDMs and PBDMs were identified using the seurat package,and their potential biological functions were explored through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.Results·Suspended IPSDMs were obtained after 29 d of in vitro differentiation.Flow cytometry and RT-qPCR confirmed that approximately 23.1%of IPSDMs expressed CD14,and IPSDMs exhibited higher expression of monocyte-macrophage marker genes compared to the U-937 cell line.All cells in the PBDM dataset were annotated as macrophages.After constructing a scmap reference dataset using PBDMs,59.8%of IPSDMs were annotated as macrophages through mapping their highly variable genes to the PBDM dataset.The remaining 40.2%of IPSDM cells could not be matched to the variable genes of PBDMs.Further manual annotation of IPSDMs revealed a composition of 97.15%macrophages,2.71%hematopoietic precursor cell-like cells,and 0.14%dendritic cells.When comparing the expression of macrophage markers,both IPSDMs and PBDMs highly expressed the classical macrophage marker CD68 gene,while IPSDMs exhibited higher expression of markers associated with tissue-resident macrophages.GO analysis of DEGs showed enrichment in the molecular functions such as ubiquitin-like protein ligase binding,cellular components such as the nuclear speck and nuclear envelope,and biological processes such as the regulation of translation.KEGG pathway enrichment indicated that the DEGs between IPSDMs and PBDMs might be related to various intracellular pathogen infections.Conclusion·Human IPSDMs and PBDMs exhibit certain similarities and heterogeneity at the single-cell transcriptional level.Transcriptomic analysis indicates that IPSDMs display more characteristics of tissue-resident macrophages.The DEGs between IPSDMs and PBDMs are potentially associated with intracellular infection immunity.
8.Comparison of human-induced pluripotent stem cell-derived macrophages with peripheral blood-derived macrophages using single-cell genomics
Yutong ZHANG ; Guojun HOU ; Nan SHEN
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(12):1477-1489
Objective·To explore the heterogeneity in single-cell genomics between human-induced pluripotent stem cell(iPSC)-derived macrophages(IPSDM)and human peripheral blood-derived macrophages(PBDM).Methods·iPSCs were differentiated into IPSDMs in vitro using a feeder-free and serum-free protocol.The expression of cluster of differentiation antigen 14(CD14)and monocyte-macrophage marker genes in IPSDMs was analyzed using flow cytometry and real-time reverse transcription quantitative polymerase chain reaction(RT-qPCR),respectively.Single-cell sequencing was then performed on IPSDMs.Simultaneously,the single-cell sequencing dataset GSE126085 was downloaded from the Gene Expression Omnibus database as a reference dataset for PBDMs.Sequencing data for both IPSDMs and PBDMs were processed and analyzed using the seurat package in R software,with PBDMs annotated using the singleR package.A reference dataset was constructed with highly variable genes from PBDMs,and the highly variable genes of IPSDMs were projected onto the PBDM dataset using the scmap package to infer IPSDMs cell identities based on variable gene similarity.IPSDMs were annotated using cell-type annotation tools and referenced against relevant studies.The expression distribution of macrophage marker genes was compared between IPSDMs and PBDMs.Differentially expressed genes(DEGs)between IPSDMs and PBDMs were identified using the seurat package,and their potential biological functions were explored through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.Results·Suspended IPSDMs were obtained after 29 d of in vitro differentiation.Flow cytometry and RT-qPCR confirmed that approximately 23.1%of IPSDMs expressed CD14,and IPSDMs exhibited higher expression of monocyte-macrophage marker genes compared to the U-937 cell line.All cells in the PBDM dataset were annotated as macrophages.After constructing a scmap reference dataset using PBDMs,59.8%of IPSDMs were annotated as macrophages through mapping their highly variable genes to the PBDM dataset.The remaining 40.2%of IPSDM cells could not be matched to the variable genes of PBDMs.Further manual annotation of IPSDMs revealed a composition of 97.15%macrophages,2.71%hematopoietic precursor cell-like cells,and 0.14%dendritic cells.When comparing the expression of macrophage markers,both IPSDMs and PBDMs highly expressed the classical macrophage marker CD68 gene,while IPSDMs exhibited higher expression of markers associated with tissue-resident macrophages.GO analysis of DEGs showed enrichment in the molecular functions such as ubiquitin-like protein ligase binding,cellular components such as the nuclear speck and nuclear envelope,and biological processes such as the regulation of translation.KEGG pathway enrichment indicated that the DEGs between IPSDMs and PBDMs might be related to various intracellular pathogen infections.Conclusion·Human IPSDMs and PBDMs exhibit certain similarities and heterogeneity at the single-cell transcriptional level.Transcriptomic analysis indicates that IPSDMs display more characteristics of tissue-resident macrophages.The DEGs between IPSDMs and PBDMs are potentially associated with intracellular infection immunity.
9.Study on the Efficacy of Cervi Colla in Yiqi Buxue Based on the Zebrafish Model
Yutong LIU ; Yong HUANG ; Hongyun MAO ; Tong ZHANG ; Jie CUI ; Mengyu LI ; Rong HOU ; Yunfeng ZHENG ; Yongqing HUA
Herald of Medicine 2023;42(12):1765-1771
Objective To quickly observe the tonic effects of Cervi Colla on enriching blood,strengthening bones and anti-aging in zebrafish model.Methods Glyphosate(Gly)was used to construct the erythrocyte injury model in adult zebrafish,and methotrexate(MTX)was used to construct the hematopoietic function injury model of juvenile zebrafish.Prednisolone(Pred)was used to establish the inhibition model of bone formation in zebrafish larvae.The ocular cell apoptosis model of zebrafish larvae was established by dibutyl phthalate(DBP).Results Cervi Colla could improve the Gly-induced abnormal erythrocyte nucleus in adult zebrafish and promote the expression of hematopoietic factors SCL and GATA1.Cervi Colla improved Pred-induced inhibition of bone formation in juvenile zebrafish,and promoted the expression of osteoblast-related gene ALP and Runx2a.The number of ocular cell apoptosis induced by DBP was decreased,and the expression of anti-apoptotic factor Bcl-2 was promoted.Conclusion Cervi Colla has significant effects on protecting erythrocyte,protecting hematopoiesis,protecting bone formation and anti-apoptosis.These effects may be related to replenish blood,anti-osteoporosis,and anti-aging.This study provides a scientific basis for the clinical application of Cervi Colla,and lays a foundation for further development and application.
10.Corrective effect of 3D printed scoliosis orthoses
Wenqiang YU ; Yutong HOU ; Chenglan HUANG ; Yunxiao YANG ; Dezhi LU ; Caiping WANG ; Jinwu WANG
Chinese Journal of Rehabilitation Theory and Practice 2023;29(4):390-395
ObjectiveTo investigate the in-brace and short-term correction of 3D-printed scoliosis orthoses. MethodsFrom July to December 2021, 36 patients with adolescent idiopathic scoliosis from Ninth People's Hospital, Shanghai Jiaotong University School of Medicine were selected to complete full-length radiographs of the spine before and immediately after wearing the orthosis. They wore the orthosis more than 20 hours a day, and took radiographs six months later. Cobb angle was calculated. They were assessed with Chinese version of the Scoliosis Research Society's outcomes instrument 22 (SRS-22) before wearing and six months follow-up. ResultsThe mean Cobb angle was (22.10±6.29)° before wearing, and it was (7.85±10.90)° immediately after wearing (t = 4.775, P < 0.01) and (14.33±0.74)° six months follow-up (t = 4.189, P < 0.01). The score of functional status of SRS-22 increased six months follow-up (Z = -2.676, P < 0.01). The Cobb angle immediately after wearing correlated with the Cobb angle six months follow-up (r = 0.826, P < 0.05). Conclusion3D-printed scoliosis orthoses can correct the scoliosis satisfactorily, in-brace and in short-term.

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