1.GSTP1-mediated inhibition of ACSL4-dependent ferroptosis via JNK pathway in DOX-induced cardiomyopathy.
Mingbo WU ; Ye ZHAO ; Dong LI ; Xueli HU ; Jiaojiao ZHOU ; Siyi CHEN ; Xin YANG ; Zegang LI ; Xiaomiao RUAN ; Jingwen YANG ; Wenwu LING
Chinese Medical Journal 2025;138(19):2498-2510
BACKGROUND:
Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC.
METHODS:
A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms.
RESULTS:
Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC.
CONCLUSIONS
This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.
2.Comparative Study of Clinical Application of Fixed-loop and Adjustable-loop in Arthroscopic Anterior Cruciate Ligament Reconstruction With Excessively Short Femoral Tunnel
Yu YIN ; Yu MEI ; Zegang WANG ; Wenjie WU ; Pengfei LIU ; Pengfeng HE ; Shouyi SONG ; Xing XIE
Chinese Journal of Minimally Invasive Surgery 2024;24(12):785-790
Objective To explore the efficacy of fixed-loop fixation and adjustable-loop fixation in arthroscopic anterior cruciate ligament(ACL)reconstruction with excessively short femoral tunnel.Methods A total of 493 patients undergoing ACL reconstruction at our hospital from January 2019 to July 2020 were reviewed,including 57 patients with femoral tunnel<30 mm and 47 patients ultimately included.According to the fixation method,they were divided into EndoButton group(n=31)and TightRope group(n=16).The International Knee Documentation Committee(IKDC)score,Lysholm score,and Tegner score were used to evaluate joint function at 6 and 12 months postoperatively,respectively.The Lachman test and anterior drawer test were used to evaluate joint laxity at 12 months postoperatively.The clinical effects of the two fixation methods were compared.Results At 6 months postoperatively,the IKDC scores of the EndoButton group and TightRope group were(64.1±11.0)points and(62.6±9.2)points,respectively,with no significant difference(t=0.464,P=0.645).The Lysholm scores were(81.9±10.6)points and(85.3±9.3)points,with no significant difference(t=-1.079,P=0.286).The Tegner scores were(2.2±0.9)points and(1.9±0.9)points,with no statistically significant difference(t=0.933,P=0.356).At 12 months postoperatively,the IKDC scores of the EndoButton group and TightRope group were(81.4±9.3)points and(78.2±9.2)points,with no statistically significant difference(t=1.068,P=0.291).The Lysholm scores were(94.6±6.1)points and(93.4±7.4)points,with no statistically significant difference(t=0.626,P=0.534).The Tegner scores were(3.8±1.0)points and(3.4±1.2)points,with no statistically significant difference(t=1.402,P=0.168).There was no significant difference in the Lachman test and front drawer test between the two groups at 12 months after surgery(Z=-0.039,P=0.969;Z=-0.294,P=0.769).Conclusion In arthroscopic ACL reconstruction surgery,both EndoButton(15 mm)and TightRope can achieve good clinical results for excessively short femoral tunnel(<30 mm).
3.Prenatal screening and prenatal diagnosis clinical laboratory diagnostic pathway
Bin QIAO ; Kunbo ZHU ; Zegang WU ; Jingwei WANG ; Hongyun ZHENG ; Yongqing TONG
Chinese Journal of Preventive Medicine 2024;58(9):1465-1472
Congenital defects and genetic diseases in the fetus are the focus of prenatal screening and prenatal diagnosis. Obstetrics and gynecology, pediatrics, medical imaging (ultrasound and magnetic resonance imaging), clinical laboratory, pathology, and other disciplines are mostly involved in this multidisciplinary work on maternal and infant health care, which aims to prevent birth defects in strict accordance with laws, regulations, and pertinent industry standards, such as the Notice of the National Health Commission on Issuing the Basic Standards for Prenatal Screening Technical Medical Institutions and the Basic Standards for Prenatal Diagnosis Technical Medical Institutions (Guowei Maternal and Child Letter [2019] No. 297). To further support the implementation of prenatal screening and diagnosis work and streamline workflow, this study has compiled the timing, inspection, and testing procedures of various projects in each link from the standpoint of the disease clinical laboratory diagnostic pathway. This approach improves communication amongst various disciplines in prenatal screening and diagnosis work and offers clinical service quality, and it also helps improve the standard of the birth population and prevent and controll severe birth defects.
4.Establishment of a clinical laboratory diagnostic pathway for hepatitis C for the teaching of laboratory diagnostics
Zegang WU ; Hongyun ZHENG ; Jian GU ; Jingwei WANG ; Qian WU ; Anyu BAO ; Yongqing TONG
Chinese Journal of Medical Education Research 2024;23(2):237-241
Objective:To establish a clinical laboratory diagnostic pathway for hepatitis C covering diagnosis, differential diagnosis, drug toxicity monitoring, and therapeutic and prognostic evaluation, and to explore a new teaching model for laboratory diagnostics based on the clinical laboratory diagnostic pathway.Methods:According to the clinical diagnosis and treatment guidelines for hepatitis C, laboratory testing strategies for different stages of diagnosis and treatment of the disease were formulated to establish a clinical laboratory diagnostic pathway for hepatitis C. The pathway was applied in the teaching for undergraduate medical students of the seven-year program of grade 2019 of The First Clinical College of Wuhan University, with those of grade 2018 as the control to receive traditional teaching. The teaching effect was compared through questionnaires and quizzes in class. The data were analyzed through the t test with the use of SPSS 19.0. Results:A clinical laboratory diagnostic pathway for hepatitis C recognized by clinicians was established, covering the entire process of clinical diagnosis, differential diagnosis, monitoring of drug side effects, and therapeutic and prognostic evaluation. The students of grade 2019 receiving the pathway-based teaching model had significant improvements in teaching quality evaluation indicators ( P<0.05), with the most marked improvement in "having mastered the key and difficult points of this lesson", with a score of (60.90±2.15) points for grade 2018 and (84.80±3.44) points for grade 2019. The total score for teaching evaluation was significantly higher in students of grade 2019 than in those of grade 2018 [(94.02±4.29) vs. (79.21±3.68)] points, P<0.05). Grade 2019 also had a significantly higher classroom quiz score than grade 2018 (94.60±5.63) vs. (78.10±4.92), P<0.01]. Conclusions:We established and applied a clinical laboratory diagnostic pathway of hepatitis C in the teaching model of laboratory diagnostics, which organically integrates laboratory diagnostics and clinical medicine, and significantly improves the quality of teaching.
5.Prenatal screening and prenatal diagnosis clinical laboratory diagnostic pathway
Bin QIAO ; Kunbo ZHU ; Zegang WU ; Jingwei WANG ; Hongyun ZHENG ; Yongqing TONG
Chinese Journal of Preventive Medicine 2024;58(9):1465-1472
Congenital defects and genetic diseases in the fetus are the focus of prenatal screening and prenatal diagnosis. Obstetrics and gynecology, pediatrics, medical imaging (ultrasound and magnetic resonance imaging), clinical laboratory, pathology, and other disciplines are mostly involved in this multidisciplinary work on maternal and infant health care, which aims to prevent birth defects in strict accordance with laws, regulations, and pertinent industry standards, such as the Notice of the National Health Commission on Issuing the Basic Standards for Prenatal Screening Technical Medical Institutions and the Basic Standards for Prenatal Diagnosis Technical Medical Institutions (Guowei Maternal and Child Letter [2019] No. 297). To further support the implementation of prenatal screening and diagnosis work and streamline workflow, this study has compiled the timing, inspection, and testing procedures of various projects in each link from the standpoint of the disease clinical laboratory diagnostic pathway. This approach improves communication amongst various disciplines in prenatal screening and diagnosis work and offers clinical service quality, and it also helps improve the standard of the birth population and prevent and controll severe birth defects.
6.Comparative Study of Clinical Application of Fixed-loop and Adjustable-loop in Arthroscopic Anterior Cruciate Ligament Reconstruction With Excessively Short Femoral Tunnel
Yu YIN ; Yu MEI ; Zegang WANG ; Wenjie WU ; Pengfei LIU ; Pengfeng HE ; Shouyi SONG ; Xing XIE
Chinese Journal of Minimally Invasive Surgery 2024;24(12):785-790
Objective To explore the efficacy of fixed-loop fixation and adjustable-loop fixation in arthroscopic anterior cruciate ligament(ACL)reconstruction with excessively short femoral tunnel.Methods A total of 493 patients undergoing ACL reconstruction at our hospital from January 2019 to July 2020 were reviewed,including 57 patients with femoral tunnel<30 mm and 47 patients ultimately included.According to the fixation method,they were divided into EndoButton group(n=31)and TightRope group(n=16).The International Knee Documentation Committee(IKDC)score,Lysholm score,and Tegner score were used to evaluate joint function at 6 and 12 months postoperatively,respectively.The Lachman test and anterior drawer test were used to evaluate joint laxity at 12 months postoperatively.The clinical effects of the two fixation methods were compared.Results At 6 months postoperatively,the IKDC scores of the EndoButton group and TightRope group were(64.1±11.0)points and(62.6±9.2)points,respectively,with no significant difference(t=0.464,P=0.645).The Lysholm scores were(81.9±10.6)points and(85.3±9.3)points,with no significant difference(t=-1.079,P=0.286).The Tegner scores were(2.2±0.9)points and(1.9±0.9)points,with no statistically significant difference(t=0.933,P=0.356).At 12 months postoperatively,the IKDC scores of the EndoButton group and TightRope group were(81.4±9.3)points and(78.2±9.2)points,with no statistically significant difference(t=1.068,P=0.291).The Lysholm scores were(94.6±6.1)points and(93.4±7.4)points,with no statistically significant difference(t=0.626,P=0.534).The Tegner scores were(3.8±1.0)points and(3.4±1.2)points,with no statistically significant difference(t=1.402,P=0.168).There was no significant difference in the Lachman test and front drawer test between the two groups at 12 months after surgery(Z=-0.039,P=0.969;Z=-0.294,P=0.769).Conclusion In arthroscopic ACL reconstruction surgery,both EndoButton(15 mm)and TightRope can achieve good clinical results for excessively short femoral tunnel(<30 mm).
7.Association between physical activity and cardiopulmonary endurance of Chinese children and adolescents
CHEN Zegang,DING Ji, WAN Qin, YIN Xiaojian, WU Huipan, DENG Ting, LI Jiawei, WANG Jinxian
Chinese Journal of School Health 2022;43(3):429-432
Objective:
To understand physical activity status and its relation with cardiopulmonary endurance among Chinese children and adolescents, so as to provide reference for cardiopulmonary endurance improvement and intervention of Chinese children and adolescents.
Methods:
During September to November 2018, a stratified cluster sampling method was used to select 4 269 children and adolescents aged 7-18 years in six major regions of China, 20 m shuttle run test and physical activity were assessed.
Results:
Average duration for daily lowintensity physical activity among boys was (31.49±30.01) min, for moderate to vigorous physical activity (68.37±46.50) min. Average duration for low intensity physical activity among girls was (34.02±31.58) min, for moderate to vigorous physical activity was (63.02±44.91) min. The number of 20 m shuttle run test for boys reached ( 36.17 ±21.94) times, and the maximal oxygen uptake per minute was (44.51±5.05) mL/kg; the number of 20 m shuttle run test for girls reached (26.59±12.56) times, and the maximal oxygen uptake per minute was (41.99±5.29) mL/kg. There were statistically significant differences in the number of 20 m shuttle run test and maximal oxygen uptake across age groups in boys ( F= 589.37 , 152.79, P <0.01), as well as that in girls ( F=305.21, 1 032.46, P <0.01). The proportion of boys and girls who met moderate to vigorous physical activity standard was 49.24% and 42.92%, respectively. Linear regression analysis showed that there was a significant positive correlation between the duration of moderate to vigorous physical activity and maximal oxygen uptake ( β=0.11, P < 0.01).
Conclusion
There is a significant correlation between moderate to vigorous physical activity with cardiorespiratory endurance among Chinese children and adolescents. Higher level of moderate to vigorous physical activity is important to help improve cardiopulmonary endurance among children and adolescents.
8. Analysis of 8 274 cases of new coronavirus nucleic acid detection and co-infection in Wuhan
Ming WANG ; Qing WU ; Wanzhou XU ; Bin QIAO ; Jingwei WANG ; Hongyun ZHENG ; Shupeng JIANG ; Junchi MEI ; Zegang WU ; Yayun DENG ; Fangyuan ZHOU ; Wei WU ; Yan ZHANG ; Zhihua LYU ; Jingtao HUANG ; Xiaoqian GUO ; Zhen CHEN ; Lina FENG ; Zunen XIA ; Di LI ; Tiangang LIU ; Pingan ZHANG ; Yongqing TONG ; Zhiliang XU ; Yan LI
Chinese Journal of Laboratory Medicine 2020;43(0):E016-E016
Objective:
To investigate the positive rate for 2019-nCoV tests and co-infections in Wuhan district.
Methods:
A total of 8 274 cases in Wuhan were enrolled in this cross-sectional study during January 20 to February 9, 2020, and were tested for 2019-nCoV using fluorescence quantitative PCR. Both respiratory tract samples (nasopharynx, oropharynx, sputum and alveolar lavage fluid) and non-respiratory tract samples (urine, feces, anal swabs, blood and conjunctival sac swabs) were collected. If both orf1ab and N genes are positive, they are classified as nucleic acid test positive group; if both orf1ab and N genes are negative, they are classified as negative group; if single gene target is positive, they are classified as suspicious group. Individuals were divided into male group and female group according to sex. At the same time, 316 patients were tested for 13 respiratory pathogens by multiplex PCR.
Results:
Among the 8 274 subjects, 2 745 (33.2%) were 2019-nCoV infected; 5 277 (63.8%) subjects showed negative results in the 2019-nCoV nucleic acid test; and 252 cases (3.05%) was not definitive (inconclusive result). The age of cases with COVID-19 patients and inconclusive cases was significantly higher than that of cases without 2019-nCoV infection (40 vs 56,
9.Analysis on HCV Genotype of Patients with Chronic Hepatitis C in Hubei
Zegang WU ; Yan LI ; Hongyun ZHENG
Journal of Modern Laboratory Medicine 2016;(1):38-40
Objective To detect the genotype of hepatitis C virus(HCV)in chronic hepatitis C(CHC)infection patients using gene sequence method and observe the distributive characteristic of HCV genotype in Hubei.Methods A total of 447 HCV-RNA-positive plasma samples were collected from chronic hepatitis C patients in Infectious Diseases Department of Renmin Hospital of Wuhan University from February 2013 to July 2015.Then NS5B region gene sequence of HCV genome were de-tected by Sanger sequencing method and compared with HCV genotype in NCBI genebank database for analyzing HCV geno-type.Results A total of 11 kinds of genotypes were detected,including genotypes 1a,1b,2a,3a,3b,6a,6b,1b/2a,1b/2k,6a/1b and 6d/6k,respectively.Detection cases of various genotypes were respectively 7 cases (1.57%),325 cases (72.71%),67 cases (14.99%),7 cases (1.57%),20 cases (4.47%),14 cases (3.13%),2 cases (0.45%),2 cases (0.45%),1 case (0.22%),1 case (0.22%)and 1 case (0.22%).Conclusion Genotype 1b was the major type of HCV-RNA genotype,fol-lowed by 2a,also other genotypes existed,which prompted that the prevalence of HCV genotype was diversity in Hubei.
10.Analysis on Gene Polymorphism of UGT1A1 Gene Promoter in Patients with Malignant Tumour
Zegang WU ; Yan LI ; Hongyun ZHENG ; Ge XIONG
Journal of Modern Laboratory Medicine 2015;(3):35-37,42
Objective To detect UGT1A1 gene promoter polymorphism with gene sequence method and analyze the distribu-tion of UGT1A1*28 and UGT1A1*6 gene polymorphism in Wuhan.Methods A total of 230 samples were collected from tumor patient in Medical Oncology Department of Renmin Hospital of Wuhan University from January 2013 to December 2014,then gene sequence of the target fragments were detected by Sanger sequencing method and analyzed patient UGT1A1 gene promoter polymorphism TA box.Results In this research examination 230 example tumor patient,198 patients (86.1%)were identified with TA6/TA6 genotype,29 patients (12.6%)were identified with TA6/TA7 genotype,3 pa-tients (1.3%)TA7/TA7 variant.Conclusion TA6/TA6 wild-typewas higher frequence in patients with malignant tumour in Wuhan.


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