1.SiO2 Induces Iron Overload and Ferroptosis in Cardiomyocytes in a Silicosis Mouse Model
Wang YONGHENG ; Li NING ; Guan YI ; LI TONG ; Zhang YUXIU ; Cao HONG ; Yu ZHIHUA ; Li ZHIHENG ; Li SHUOYAN ; Hu JIAHAO ; Zhou WENXIN ; Qin SISI ; Li SHUANG ; Yao SANQIAO
Biomedical and Environmental Sciences 2024;37(6):617-627
Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO2-induced cardiac injury using a mouse model. Methods Male C57BL/6 mice were intratracheally instilled with SiO2 to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed. Results SiO2 altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO2-induced mitochondrial damage and myocardial injury.SiO2 inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion Iron overload-induced ferroptosis contributes to SiO2-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO2 cardiotoxicity,potentially via modulation of the Nrf2 pathway.
2.Etiological analysis of hydronephrosis in adults:A single-center cross-sectional study
Silu CHEN ; Haiju WANG ; Yucai WU ; Zhihua LI ; Yanbo HUANG ; Yuhui HE ; Yangyang XU ; Xue-Song LI ; Hua GUAN
Journal of Peking University(Health Sciences) 2024;56(5):913-918
Objective:To investigate the etiological distribution of hydronephrosis caused by upper uri-nary tract obstruction in adult patients and to improve the diagnostic accuracy for this condition.Me-thods:The clinical information of adult patients with newly diagnosed hydronephrosis in Upper Urinary Tract Repair Outpatient Clinic of Peking University First Hospital from May 2020 to May 2021 were pro-spectively and continuously collected.Patients with ureteral calculi or upper urinary tract tumor were ex-cluded.A total of 767 patients were involved.The underlying causes of upper urinary tract obstruction were identified by senior urological surgeons according to symptoms,medical history,physical examina-tion,and a range of diagnostic imaging techniques including ultrasound,computed tomography(CT),magnetic resonance imaging(MRI),retrograde pyelography,antegrade pyelography,radionuclide reno-gram and ureteroscopy.Results:Among the 767 patients,359(46.8%)were male and 408(53.2%)were female.The median age of these patients was 37 years(range,14-84 years).Hydronephrosis was observed at left-sided in 357 cases(46.6%),right-sided in 251 cases(32.7%),and bilateral in 159 cases(20.7%).The causes of hydronephrosis were classified as follows:(1)Non-iatrogenic factors were found in 464 cases(60.5%).These included urinary malformations in 355 cases(76.5%),infec-tion in 29 cases(6.3%),pelvic lipomatosis and/or cystitis glandularis in 23 cases(5.0%),ureteral en-dometriosis in 18 cases(3.9%),retroperitoneal fibrosis in 15 cases(3.2%),trauma in 7 cases(1.5%)and other non-iatrogenic factors in 12 cases(2.6%).Some of these patients had multiple non-iatrogenic causes.Among the 355 cases with urinary system malformations,252 cases(71.0%)had ureteropelvic junction obstruction.(2)Iatrogenic ureteral injuries accounted for 210 cases(27.4%),including 112 cases(53.3%)of urological surgical injuries,51 cases(24.3%)of radiotherapy for malignant tumor re-lated injuries,34 cases(16.2%)of gynecological and obstetrical surgical injuries,and 13 cases(6.2%)of general surgical injuries.(3)The cause of hydronephrosis remained unknown in 93 cases(12.1%).Conclusion:Hydronephrosis in adults due to upper urinary tract obstruction has a diverse range of cau-ses,with urinary malformations and iatrogenic ureteral injuries being significant contributors.Urological surgeon involved in upper urinary tract reconstruction should be familiar with these potential causes to fa-cilitate accurate diagnosis and effective treatment.
3.Inhibition of Fatty Acid β-Oxidation by Fatty Acid Binding Protein 4 Induces Ferroptosis in HK2 Cells Under High Glucose Conditions
Jiasi CHEN ; Keping WU ; Yan LEI ; Mingcheng HUANG ; Lokyu CHENG ; Hui GUAN ; Jiawen LIN ; Ming ZHONG ; Xiaohua WANG ; Zhihua ZHENG
Endocrinology and Metabolism 2023;38(2):226-244
Background:
Ferroptosis, which is caused by an iron-dependent accumulation of lipid hydroperoxides, is a type of cell death linked to diabetic kidney disease (DKD). Previous research has shown that fatty acid binding protein 4 (FABP4) is involved in the regulation of ferroptosis in diabetic retinopathy. The present study was constructed to explore the role of FABP4 in the regulation of ferroptosis in DKD.
Methods:
We first detected the expression of FABP4 and proteins related to ferroptosis in renal biopsies of patients with DKD. Then, we used a FABP4 inhibitor and small interfering RNA to investigate the role of FABP4 in ferroptosis induced by high glucose in human renal proximal tubular epithelial (HG-HK2) cells.
Results:
In kidney biopsies of DKD patients, the expression of FABP4 was elevated, whereas carnitine palmitoyltransferase-1A (CP-T1A), glutathione peroxidase 4, ferritin heavy chain, and ferritin light chain showed reduced expression. In HG-HK2 cells, the induction of ferroptosis was accompanied by an increase in FABP4. Inhibition of FABP4 in HG-HK2 cells changed the redox state, sup-pressing the production of reactive oxygen species, ferrous iron (Fe2+), and malondialdehyde, increasing superoxide dismutase, and reversing ferroptosis-associated mitochondrial damage. The inhibition of FABP4 also increased the expression of CPT1A, reversed lipid deposition, and restored impaired fatty acid β-oxidation. In addition, the inhibition of CPT1A could induce ferroptosis in HK2 cells.
Conclusion
Our results suggest that FABP4 mediates ferroptosis in HG-HK2 cells by inhibiting fatty acid β-oxidation.
4.Feasibility and safety of robotic-assisted laparoscopic adrenalectomy with the assistance of three-dimensional reconstruction of computed tomography image to treat huge adrenal tumors
Heng LI ; Jun YANG ; Fan LI ; Yuchao LU ; Chunguang YANG ; Xing ZENG ; Zheng LIU ; Zhihua WANG ; Wei GUAN ; Xiao YU ; Zhiquan HU ; Shaogang WANG
Chinese Journal of Urology 2023;44(12):897-900
Objective:Efficacy and safety of robot-assisted laparoscopic adrenalectomy as a treatment for large adrenal tumors.Three-dimensional(3D) reconstruction can effectively assist in preoperative planning of robotic adrenalectomy and reduce potential complications.Methods:We retrospectively reviewed the relevant information of patients who had a preoperative 3D reconstruction and underwent RA for adrenal masses larger than 10 cm. Thirteen male patients and sixteen female patients were included. The median(range) age was 43(25, 57) years old and the median tumor diameter was 12.1(10.3, 16.2) cm. The patients underwent preoperative CT enhancement scanning, and three-dimensional images were reconstructed based on the examination data. Robot-assisted laparoscopic adrenalectomy was performed under general anesthesia in 29 cases in this cohort.Results:All surgeries were completed successfully without major complications such as massive bleeding, secondary surgery, or even patient death. The median operative time was 131 (80, 245) min, and the median intraoperative bleeding was 330 (50, 2 200 ml) ml. 9 patients received blood transfusions. There were 11 cases of pheochromocytoma (37.9%), 10 cases of adenocarcinoma (34.5%) as well as 2 cases of teratoma (6.9%) and 6 cases of cortical carcinoma (20.7%). The patients were followed up for a median of 30 months after surgery. Except for 3 cases lost to follow-up and 2 patients with cortical cancer who developed recurrence or metastasis after surgery and died at 16 and 23 months after surgery, respectively, the remaining 24 cases have survived to date.Conclusions:RA is a safe and effective treatment for huge adrenal tumors. The 3D reconstruction could help the preoperative planning of RA and reduce potential complications.
5.The application of Hood technique in robotic-assisted radical prostatectomy
Jun YANG ; Jia HU ; Wei GUAN ; Zheng LIU ; Zhihua WANG ; Zhiquan HU ; Qianyuan ZHUANG ; Shaogang WANG
Chinese Journal of Urology 2022;43(3):176-180
Objective:To explore the feasibility, safety and short-term effect of the Hood technique in robotic-assisted radical prostatectomy (RARP).Methods:The data of 24 patients with localized prostate cancer underwent RARP with Hood technique From June 2020 to March 2021 were retrospectively reviewed. The mean age was 67.8 (57-76) years, and the mean body mass index was 25.17(18.31-32.54)kg/m 2. The mean tPSA value was 18.36(4.21-67.57)ng/ml and the mean biopsy Gleason score was 7.3 (6-8). In term of the clinical T stage, the 24 cases were composed of the T 1c stage in 1 case, T 2a stage in 5 cases, T 2b stage in 4 cases and T 2c stage in 14 cases. During Hood technique, the anterior bladder were limitedly isolated without exposing the outline of pelvis and prostate. Results:All the cases were completed robotically without conversion, transfusion or positive surgical margin. The average robot-assisted operation time was 84.5(63-110) mins. Estimated blood loss was 75.3(20-180) ml. The average time for maintaining the drain was 3.7(3-5) days. The mean postoperative hospital stay was 7.1(4-11) days. The mean catheterization time was 7.3(6-9) days after surgery. 23 patients achieved continence immediately after catheter removal, while 1 patient had continence full-recovery 2 weeks after surgery. The mean surgical Gleason score was 7.9 (6-9). In term of the surgical T stage, the 24 cases were composed of the pT 2a stage in 4 case, T 2b stage in 6 cases, T 2c stage in 14 cases.During 3-12 months’ follow-up, no biochemical recurrence was found. Conclusions:Hood technique were safe and valid in RARP with excellent immediate continence recovery. It facilitated Retzius sparing in a convenient approach with low positive surgical margin rate.
6.Effectiveness of the proactive risk prevention nursing procedure in patients undergoing digestive endoscopy
Ying LIU ; Zhihua GUAN ; Kunkun LI ; Lei ZHANG
Chinese Journal of Modern Nursing 2022;28(28):3976-3978
Objective:To explore the effect of proactive risk prevention nursing procedure in patients undergoing digestive endoscopy.Methods:Using convenience sampling method, patients who underwent digestive endoscopy in Zhengzhou Central Hospital affiliated to Zhengzhou University from August 2017 to August 2018 were selected as the control group ( n=75) . Patients who underwent digestive endoscopy in Zhengzhou Central Hospital affiliated to Zhengzhou University from March 2019 to March 2020 were selected as the observation group ( n=75) . The patients in the control group received the routine nursing, and the patients in the observation group were treated the proactive risk prevention nursing procedure. The adverse reactions and nursing satisfaction of the two groups were compared. Results:The total incidence of adverse reactions in the observation group was lower than that in the control group, and the nursing satisfaction was higher than that in the control group, with statistical differences ( P<0.05) . Conclusions:The proactive risk prevention nursing procedure can reduce the incidence of adverse reactions in patients undergoing digestive endoscopy and improve nursing satisfaction.
7.20()-Protopanaxatriol promotes the binding of P53 and DNA to regulate the antitumor network multiomic analysis.
Zhihua WANG ; Wenbo WU ; Xiangchen GUAN ; Shuang GUO ; Chaowen LI ; Ruixue NIU ; Jie GAO ; Min JIANG ; Liping BAI ; Elaine Laihan LEUNG ; Yuanyuan HOU ; Zhihong JIANG ; Gang BAI
Acta Pharmaceutica Sinica B 2020;10(6):1020-1035
Although the tumor suppressor P53 is known to regulate a broad network of signaling pathways, it is still unclear how certain drugs influence these P53 signaling networks. Here, we used a comprehensive single-cell multiomics view of the effects of ginsenosides on cancer cells. Transcriptome and proteome profiling revealed that the antitumor activity of ginsenosides is closely associated with P53 protein. A miRNA-proteome interaction network revealed that P53 controlled the transcription of at least 38 proteins, and proteome-metabolome profiling analysis revealed that P53 regulated proteins involved in nucleotide metabolism, amino acid metabolism and "Warburg effect". The results of integrative multiomics analysis revealed P53 protein as a potential key target that influences the anti-tumor activity of ginsenosides. Furthermore, by applying affinity mass spectrometry (MS) screening and surface plasmon resonance fragment library screening, we confirmed that 20()-protopanaxatriol directly targeted adjacent regions of the P53 DNA-binding pocket and promoted the stability of P53-DNA interactions, which further induced a series of omics changes.
8.DPHL:A DIA Pan-human Protein Mass Spectrometry Library for Robust Biomarker Discovery
Zhu TIANSHENG ; Zhu YI ; Xuan YUE ; Gao HUANHUAN ; Cai XUE ; Piersma R. SANDER ; Pham V. THANG ; Schelfhorst TIM ; Haas R.G.D. RICHARD ; Bijnsdorp V. IRENE ; Sun RUI ; Yue LIANG ; Ruan GUAN ; Zhang QIUSHI ; Hu MO ; Zhou YUE ; Winan J. Van Houdt ; Tessa Y.S. Le Large ; Cloos JACQUELINE ; Wojtuszkiewicz ANNA ; Koppers-Lalic DANIJELA ; B(o)ttger FRANZISKA ; Scheepbouwer CHANTAL ; Brakenhoff H. RUUD ; Geert J.L.H. van Leenders ; Ijzermans N.M. JAN ; Martens W.M. JOHN ; Steenbergen D.M. RENSKE ; Grieken C. NICOLE ; Selvarajan SATHIYAMOORTHY ; Mantoo SANGEETA ; Lee S. SZE ; Yeow J.Y. SERENE ; Alkaff M.F. SYED ; Xiang NAN ; Sun YAOTING ; Yi XIAO ; Dai SHAOZHENG ; Liu WEI ; Lu TIAN ; Wu ZHICHENG ; Liang XIAO ; Wang MAN ; Shao YINGKUAN ; Zheng XI ; Xu KAILUN ; Yang QIN ; Meng YIFAN ; Lu CONG ; Zhu JIANG ; Zheng JIN'E ; Wang BO ; Lou SAI ; Dai YIBEI ; Xu CHAO ; Yu CHENHUAN ; Ying HUAZHONG ; Lim K. TONY ; Wu JIANMIN ; Gao XIAOFEI ; Luan ZHONGZHI ; Teng XIAODONG ; Wu PENG ; Huang SHI'ANG ; Tao ZHIHUA ; Iyer G. NARAYANAN ; Zhou SHUIGENG ; Shao WENGUANG ; Lam HENRY ; Ma DING ; Ji JIAFU ; Kon L. OI ; Zheng SHU ; Aebersold RUEDI ; Jimenez R. CONNIE ; Guo TIANNAN
Genomics, Proteomics & Bioinformatics 2020;18(2):104-119
To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.
9. Study of the prevalence and disease burden of chronic disease in the elderly in China
Linmin WANG ; Zhihua CHEN ; Mei ZHANG ; Zhenping ZHAO ; Zhengjing HUANG ; Xiao ZHANG ; Chun LI ; Yunqi GUAN ; Xuan WANG ; Zhihui WANG ; Maigeng ZHOU
Chinese Journal of Epidemiology 2019;40(3):277-283
Objective:
To understand the prevalence and disease burden of major chronic diseases in the elderly in China and provide scientific basis for the prevention and control of chronic diseases and for the rational allocation of health resources.
Methods:
We analyzed the prevalence of chronic diseases in residents aged ≥60 years in China by using national and provincial surveillance data of chronic diseases and related risk factors in China. We conducted the analysis on the burden of chronic diseases in the elderly in China by using the data of global burden of disease.
Results:
The prevalence rates of hypertension, diabetes and hypercholesterolemia were 58.3
10.Performance evaluation of the automated SNPs analyzer for the detection of JAK2 V617F mutation
Weizhe MA ; Lujia CHEN ; Zhihua KANG ; Xiao XU ; Yuming CHEN ; Xinju ZHANG ; Yan WANG ; Ming GUAN
Chinese Journal of Laboratory Medicine 2018;41(6):470-474
Objective To test and evaluate the JAK2 gene V617F mutation in patients with myeloproliferative tumors based on i-densy IS-5320 platform according to ISO15189 accreditation requirements.Methods Instrument performance verification.Selected from December 2014 to February 2017, 20 cases of JAK2 V617F mutation positive peripheral blood samples from Huashan Hospital of the Shanghai FuDan University Medical College and 20 cases of peripheral blood samples with negative JAK2V617F mutation.The Realtime PCR with TaqMan MGB probe was selected as the control method to verify and evaluate the accuracy of testing JAK 2 V617F mutation on i-densy IS-5320 platform.Whole blood samples were used to evaluate the reproducibility , cross-contamination and anti-interference ability of this platform.The ability of mutation load was verified by detecting mixtures of human erythnoleukemia cells and colorectal cancer cell HCT116 with 12 different proportions.Results I-densy IS-5320 platform and TaqMan MGB probe real-time fluorescence quantitative PCR show the same result .The within-run reproducibility and between-run reproducibility are both 100%.There is no observed contamination .High bilirubin and high triglyceride blood samples have no obvious interference on mutation detection .The mutation ratio with a load as low as 0.25%could be tested stably by i-densy IS-5320 platform.The detecting peak of melting curve can reflect the ratio of JAK2 V617F mutation to some extent.Conclusions I-densy IS-5320 can detect the mutation of JAK2 V617F gene in the whole blood directly.It has high sensitivity, accuracy and stability, and is easy to operate, and also can reflect the mutation load of JAK2 V617F, which could meet the clinical requirements for the detection of mutations.

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