1.Subchronic exposure to benzoapyrene results in lung tissue cell damage caused by ferroptosis in mice
Chaoli ZHOU ; Shihan DING ; Hui HE ; Zhirui MA ; Jie CHEN ; Xingdi GUO ; Yi LYU ; Jinping ZHENG
Journal of Environmental and Occupational Medicine 2025;42(8):971-977
Background Exposure to benzo[a]pyrene (BaP) may impair lung function through various mechanisms; however, it remains uncertain whether BaP induces ferroptosis in lung tissue cells, resulting in lung function impairment. Objective To investigate the ferroptosis of lung tissue cells triggered by subchronic BaP exposure in mice and its correlation with lung injury, and to explore the function of ferroptosis in BaP-induced lung tissue damage. Method Seventy-two healthy 3-weeks-old male C57BL/6J mice were acclimatized for 1 week and then randomly divided into six groups: control group (corn oil 10 mL·kg−1), low-dose BaP group (2.5 mg·kg−1), medium-dose BaP group (5 mg·kg−1), high-dose BaP group (10 mg·kg−1), BaP+ferrostatin-1 (Fer-1) group (10 mg·kg−1+1 mg·kg−1), and Fer-1 group (1 mg·kg−1), with 12 mice each group. Corn oil and BaP were administered via gavage every other day, followed by an intraperitoneal injection of Fer-1 the subsequent day, throughout a period of 90 d. Whole-body plethysmography was applied to detect lung function; hematoxylin-eosin staining (HE) and Masson staining were used to observe lung tissue injury and fibrosis; microscopy of alveolar epithelial cells was conducted to reveal mitochondrial morphology; biochemical assays were used to measure the content of tissue iron, malondialdehyde (MDA), and glutathione (GSH), as well as the activity of glutathione peroxidase (GSH-Px); Western blotting and real-time quantitative PCR (RT-qPCR) analyses were performed to reveal the protein and mRNA expression of ferroptosis markers. Results Compared to the control group, the high-dose BaP group showed a significant increase in expiration time (Te) (P<0.01), and a significant decrease in ratio rate of achieving peak expiratory flow (Rpef), tidal volume (TVb), peak inspiratory flow (PIF), minute volume (MVb), and peak expiratory flow (PEF) (P<0.05 or 0.01). Based on the results of HE and Masson staining, partial destruction of alveolar structures, thickening of alveolar walls, infiltration of inflammatory cells, significant thickening of tracheal walls and a large deposition of collagen fibers in lung tissue were observed in the medium- and high-dose BaP groups. By microscopy, the alveolar epithelial cells exposed to low-dose BaP showed condensed chromatin, and the mitochondria exposed to medium and high-dose BaP showed wrinkles, increased mitochondrial membrane density, and diminished mitochondrial cristae. Compared to the control group, in the medium- and high-dose BaP groups, the lung tissue iron content and the expression levels of ACSL4 protein and mRNA significantly elevated (P<0.01 or 0.05), while the mRNA expression level of SLC7A11 significantly decreased (P<0.05); in the high-dose BaP group, the MDA content, COX2 protein, and PTGS2 mRNA expression levels significantly increased (P<0.05 or 0.01), GSH content and GSH-Px activity, GPX4 protein and mRNA expression levels, and the expression level of SLC7A11 protein significantly decreased (P<0.01 or 0.05). The ferroptosis inhibitor Fer-1 markedly reversed respiratory function, morphology, mitochondrial alterations, and the aforementioned ferroptosis-related biochemical indicators. Conclusion Subchronic exposure to BaP can induce ferroptosis in mice lung tissue cells, resulting in compromised lung function.
2.Diagnostic quality analysis of negative etiological pulmonary tuberculosis test results in Wuhan
Jianjie WANG ; Jun CHEN ; Ling XU ; Zhirui BAI ; Zhengbin ZHANG ; Yuehua LI
International Journal of Laboratory Medicine 2024;45(18):2197-2200,2206
Objective To analyze the diagnosis status of negative etiological pulmonary tuberculosis test re-sults in Wuhan,and to provide scientific basis for improving the diagnosis strategy of etiological negative pul-monary tuberculosis.Methods From January 1 to February 28,2019,a total of 241 patients with negative eti-ological tuberculosis who were registered,reported and treated in 1 municipal and 2 district-level designated hospitals were selected.The medical record data,chest imaging examination and laboratory examination re-sults of the selected patients were reviewed and extracted,and the quality of etiological examination and ima-ging examination of patients with negative etiological pulmonary tuberculosis were analyzed.Results Among the 241 patients,88.8%(214/241)of the patients met the diagnostic criteria for negative etiological pulmona-ry tuberculosis,and 96.3%(232/241)of the patients had chest imaging examinations that were consistent with the original diagnostic results.Patients received sputum smear examination,sputum culture,and molecu-lar biology test accounted for 97.9%(236/241),73.9%(178/241)and 65.6%(158/241),respectively.Patients received anti-tuberculosis antibody test,tuberculin skin test,y-interferon release and diagnostic anti-infection treatment accounted for 54.8%(132/241),46.5%(112/241),26.1%(63/241),and 53.1%(128/241),respec-tively.The sputum culture detection rate of urban area was higher than those of central and remote urban are-as,the rate of central urban area was higher than that of remote urban areas,and the molecular biology detec-tion rate of urban area was higher than those of central and remote urban area,with statistical significance(P<0.001).The detection rate of anti-tuberculosis antibody of urban area was lower than that of central ur-ban area,and the differences were statistically significant(P<0.001).The rate of diagnostic anti-infective therapy of central urban area was higher than that of urban area and the remote urban area,and the rate in ur-ban area was higher than that of remote urban area,and the differences were statistically significant(P<0.001).Conclusion It is necessary to further standardize the diagnosis of negative etiological pulmonany tu-berculosis of designated tuberculosis hospitals.The proportion of diagnostic anti-infection treatment and auxil-iary examination at the municipal level needs to be increased,and the frequency and items of laboratory etio-logical examination at the district level need to be increased.
3.Pharmacological inhibition of BAP1 recruits HERC2 to competitively dissociate BRCA1-BARD1, suppresses DNA repair and sensitizes CRC to radiotherapy.
Xin YUE ; Tingyu LIU ; Xuecen WANG ; Weijian WU ; Gesi WEN ; Yang YI ; Jiaxin WU ; Ziyang WANG ; Weixiang ZHAN ; Ruirui WU ; Yuan MENG ; Zhirui CAO ; Liyuan LE ; Wenyan QIU ; Xiaoyue ZHANG ; Zhenyu LI ; Yong CHEN ; Guohui WAN ; Xianzhang BU ; Zhenwei PENG ; Ran-Yi LIU
Acta Pharmaceutica Sinica B 2023;13(8):3382-3399
Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.
4.A longitudinal survey of death anxiety in patients with newly diagnosed cancer
Furong CHEN ; Yongyi CHEN ; Xiangyu LIU ; Zhirui XIAO ; Xianghua XU
Chinese Mental Health Journal 2023;37(12):1052-1058
Objective:To investigate the level of death anxiety and its related factors in patients with newly diagnosed cancer at different stages.Methods:A total of 266 cancer patients in a tertiary oncology hospital were se-lected and investigated at admission(Tl),discharge(T2),and 1 month after discharge(T3).They were assessed with the self-compiled general information questionnaire,Templer's Death Anxiety Scale(T-DAS),Acceptance and Action Questionnaire Second Edition(AAQ-Ⅱ.),and the Chinese version of the Meaning in Life Questionnaire(C-MLQ).The Kruskal-Wallis H test and generalized estimating equation were used to analyze the level of death anxi-ety and its influencing factors in cancer patients at different time points.Results:The Kruskal-Wallis H test showed that the total T-DAS scores and the difference in the scores of the four dimensions were statistically significant at three time points(Ps<0.01),with the highest T1 score and the lowest T3 score.The results of generalized estima-ting equation showed that male gender(β=1.25),junior high school education(β=2.59),worker(β=1.46),farmer(β=1.67),respiratory(β=1.74),digestive system tumor(β=2.51),and AAQ-Ⅱ score(β=0.23)posi-tively predicted death anxiety in patients with cancer.Head and neck(β=-1.73),breast tumors(β=-1.84),stage Ⅰ(β=-2.58)and stage Ⅱ tumors(β=-2.11),and C-MLQ score(β=-0.15)negatively predicted death anxiety in patients with cancer.Conclusion:Death anxiety in patients with newly diagnosed cancer is highest on ad-mission and gradually relieves after discharge.
5.Arctigenin regulates the effect of miR-21 on hypoxia-reoxygenation-induced pyroptosis of cardiomyocytes
Xiaoxia YAO ; Zhirui CHEN ; Jing LEI ; Ping TANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2022;43(5):763-768
【Objective】 To investigate the effect and mechanism of arctigenin (ARG) on hypoxia-reoxygenation (H/R) induced pyroptosis of cardiomyocytes. 【Methods】 H9C2 cells were cultured in vitro, and underwent hypoxia for 2 hours and reoxygenation for 4 hours to establish H/R cell injury model. The cells were divided into control group (Control), model group (H/R), ARG group, miR-21 simulation group (miR-21 mimic), and ARG+miR-21 inhibitor group (ARG+miR-21 inhibitor). TUNEL staining was used to detect the pyroptosis index of H9C2 cells; the lactate dehydrogenase (LDH) kit was used to detect the release of LDH in each group of cells; the enzyme-linked immunosorbent assay (ELISA) was used to detect the content of interleukin-1β (IL-1β) and interleukin-18 (IL-18). Western blotting was used to detect the expressions of pyroptosis-related proteins (Caspase-1, GSDMD, IL-1β and IL-18) in each group. 【Results】 Compared with those in the control group, the pyroptosis index, the release of LDH, IL-1β and IL-18, and the protein expressions of Caspase-1p20, GSDMD-N, IL-1β and IL-18 in the H/R group were significantly increased (P<0.01). Compared with H/R group, ARG group and miR-21 mimic group had significantly reduced pyroptosis index, LDH, IL-1β and IL-18 release, and protein expressions of Caspase-1 p20, GSDMD-N, IL-1β and IL-18 (P<0.01), and the above-mentioned index changes could be reversed after treatment with +miR-21 inhibitor. 【Conclusion】 ARG can inhibit H/R-induced pyroptosis of cardiomyocytes, and its mechanism is related to the promotion of miR-21 expression.
6.Experimental study of the effects of Yunpi-Xiefei-Huatan Decoction on the expression of EGFR and MUC5AC in lung tissue of asthmatic rat model
Na CHEN ; Zhu CHEN ; Yuan ZHANG ; Shengzuan LI ; Zhi ZHENG ; Heping YANG ; Diqin LUO ; Zhirui ZHANG
International Journal of Traditional Chinese Medicine 2021;43(9):880-886
Objective:To observe the effect of Yunpi-Xiefei-Huatan Decoction on airway mucus hypersecretion of asthmatic rats and its regulation on epidermal growth factor receptor (EGFR) / mucin 5AC (MUC5AC) signal pathway. Methods:Seventy SD rats were randomly divided into normal group, model group, high dose group, medium dose group, low dose group, western medicine group and combined group, with 10 rats in each group. Except the normal group, the other groups were sensitized with 1 ml ovalbumin and aluminum hydroxide mixture to establish the asthma rat model. On the 16th day of the experiment, the high, medium and low dose groups were given Yunpi-Xiefei-Huatan Decoction of 40, 20, 10 g/kg, respectively, the western medicine group was given carboxymethylstein tablets of 150 mg/kg, and the combined group was given Yunpi-Xiefei-Huatan Decoction of 20 g/kg and carboxymethylstein tablets of 150 mg/kg, once a day, for 4 weeks. The levels of tumor necrosis factor (TNF-α) and interleukin-13 (IL-13) in serum of rats were detected by Enzyme-linked Immunosorbent Assay (ELISA), the total number and classification of leukocytes in BALF were observed by Wright Giemsa staining, the pathological changes of lung tissue were observed by glycogen staining (PAS). The protein expression of epidermal growth factor receptor (EGFR) and MUC5AC (MUC5AC) were detected by Western blotting, and the mRNA expression of EGFR and MUC5AC was detected by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). Results:Compared with the model group, the level of IL-13 and TNF-α in the high, medium and low dose groups of traditional Chinese medicine, western medicine group and combined group was significantly decreased ( P<0.05). The levels of WBC, eosinophils and neutrophils in rat alveolar lavage fluid were significantly decreased ( P<0.05). The expression of EGFR (0.466 ± 0.023, 0.354 ± 0.047, 0.667 ± 0.066, 0.553 ± 0.065, 0.290 ± 0.033 vs. 0.782 ± 0.047) and MUC5AC (0.424 ± 0.022, 0.313 ± 0.033, 0.603 ± 0.051, 0.495 ± 0.041, 0.243 ± 0.024 vs. 0.806 ± 0.090) significantly decreased ( P<0.05), the m RNA expression of EGFR (2.302 ± 0.321, 2.549 ± 0.623, 3.084 ± 0.453, 2.585 ± 0.314, 1.810 ± 0.379 vs. 4.101 ± 0.567), MUC5AC (3.243 ± 0.742, 3.283 ± 1.064, 4.419 ± 0.572, 3.817 ± 0.637, 2.469 ± 0.424 vs. 5.840 ± 0.661) in the high, medium and low dose groups, western medicine group and combined group was significantly decreased ( P<0.05). Conclusion:Yunpi-Xiefei-Huatan Decoction ccould inhibit asthma, and its mechanism mightbe related to the EGFR/MUC5AC signaling pathway.
7.Development Status of Irreversible Electric Perforated Tumor Ablation Device.
Tianshuai HE ; Kun TAN ; Qianqian SUN ; Zhirui ZHANG ; Xue CHEN ; Yi LYU ; Rongqian WU
Chinese Journal of Medical Instrumentation 2021;45(6):655-661
This study firstly introduced the mechanism, benefits and applications of irreversible electroporation(IRE) for tumor ablation. In addition, this study also introduced the most advanced IRE systems cleared by FDA or CFDA and IRE research equipment. The clinically licensed IRE systems include the Nanoknife 3.0 of Angiodynamics, the Dophi
Electricity
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Electroporation
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Heart Rate
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Humans
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Neoplasms/therapy*
8.Study on the Effects of Deoxyschizandrin on the Proliferation ,Migration and Invasion of Human Nasopharyngeal Carcinoma Cell HONE- 1 via Met/PI 3K/Akt Signaling Pathway
Tengxiang CHEN ; Li LIANG ; Zhirui ZENG ; Shan LEI ; Jingya WANG ; Yuanmei SUN ; Jinzhi LAN ; Yan XUE
China Pharmacy 2020;31(19):2376-2381
OBJECTIVE:To study the effects and potential mechani sm of deoxyschizandrin on the proliferation ,migration and invasion of nasopharyngeal carcinoma cell HONE- 1. METHODS :HONE-1 cell was set as cell model ,while CCK- 8 test,wound healing assay and Transwell chamber test were used to detect the proliferation ,migration and invasion ability changes of HONE- 1 cells after treatment with different concentrations [ 0(blank control ),10,20,40 μmol/L] of deoxyschizandrin. Computer molecular docking was performed to analyze the binding ability between deoxyschizandrin and Met protein. Western blotting assay was used to detect the relative protein expressions of p-Met ,p-PI3K,p-Akt,Bcl-2 and N-cadherin in cells. RESULTS :Compared with blank control ,the proliferation ,migration and invasion ability of cells after treated with 10,20,40 μmol/L deoxyschizandrin were all decreased significantly (P<0.05). Results of molecular docking revealed that deoxyschizandrin could stably bind with the activity pocket of Met protein. Results of Western blotting assay demonstrated that compared with blank control ,10,20,40 μmol/L deoxyschizandrin all decreased the relative protein expressions of p-Met ,p-PI3K,p-Akt,Bcl-2 and N-cadherin in cells significantly(P<0.05). CONCLUSIONS :Deoxyschizandrin can inhibit the proliferation ,migration and invasion of HONE- 1 cell via inhibiting the activation of Met/PI 3K/Akt signaling pathway.
9. Electrocardiographic characteristics of idiopathic ventricular arrhythmias originating from the tricuspid annulus regions
Xuliang CHEN ; Ping LI ; Shujie WU ; Zhirui LIU ; Jiafeng LIN ; Xueqiang GUAN
Chinese Journal of Cardiology 2018;46(8):611-616
Object:
To explore the electrocardiographic characteristics of ventricular arrhythmias (VAs) originating from tricuspid annulus region.
Methods:
Present study included 169 consecutive patients undergoing catheter ablation of VAs from tricuspid annulus origin in our department from August 2007 to September 2016. Based on the origin sites, the patients were divided into two subgroups, the free wall group (81 cases) and septal wall group (88 cases). Based on the location, patients in the free wall group were classified into anterolateral (22 cases), lateral (26 cases) and posterolateral (33 cases) subgroups. Patients in the septal group were classified into anteroseptal (10 cases), midseptal (71 cases) and posteroseptal (7 cases) subgroups. We analyzed the electrocardiographic features of these patients and in 87 patients with PVCs/VT originating from right ventricular outflow tract.
Results:
(1) A positive R wave inⅠ, aVL, V5-V6 leads were found among most of patients, only few cases originating from tricuspid annulus anteroseptum group and tricuspid annulus anterolateral group demonstrated qr or qs pattern in aVL lead. 97.53% (79/81) patients demonstrated rS pattern in V1-V3 leads with VAs originating from tricuspid annulus free wall, and 9/10 patients demonstrated rS pattern in V1 lead with VAs originating from anteroseptum, and 97.44% (76/78) patients demonstrated QS pattern in V1 lead with VAs originating from midseptum and posteroseptum. Precordial lead transition zone was on or behind V3 for tricuspid annulus free wall group (96.3%, 78/81), but in front of V3 for tricuspid annulus septum wall group (47.73%, 42/88) (
10.The influence of different modes of transport on emergency intervention time in patients with ST segment elevation myocardial infarction
Panpan CHEN ; Shujuan DONG ; Jingchao LI ; Haijia YU ; Huihui LI ; Juntao WANG ; Leimin ZHANG ; Zhirui LI ; Kun QIAO ; Yuanyuan TAN ; Chunling KONG ; Yingjie CHU
Chinese Journal of Emergency Medicine 2017;26(7):756-762
Objective To study the time extended for getting emergency intervention in different modes of transportation and factors influencing the modes of transportation of patients with ST elevation myocardial infarction (STEMI).Methods A total of 564 consecutive patients with STEMI admitted from September 2013 to June 2016 were enrolled in the study.The clinical data about time consumed for getting emergency intervention and modes of transportation were collected.Results According to the mode of transportation,patients were divided into three groups:emergency care system (EMS) transportation group (n =96),self-transportation group (n =206) and referral group in which the patients were sent in from other hospitals (n =262).EMS transportation group had significantly shorter total ischemic time before emergency treatment than self-transportation group (229 rin vs.418 min,P < 0.05) and referral group (229 min vs.512 rin,P < 0.05),and significantly shorter length of pre-hospital time than self-arrival group (55 min vs.110 min;P<0.05) and referral group (55 min vs.372 min;P<0,05).The referral group had longer pre-hospital time and the self-transportation group had longer door-to-balloon time,but there was no difference in total ischemic time between the self-arrival and referral group (Z =-1.882,P =0.068).Multivariate logistic regression was used to analyze influence factors in mode of transportation:(1) patients characterized with high school or university education,profession of civil service,and their transportation distance more than 30 km were greater in number than referral group (P < 0.05);(2) patients identified with senior middle school education,staff member of public sectors or company,their transportation distance less than 30 km,and with killip grade above Ⅱ were more likely to have EMS transport (P < 0.05);(3) patients defined as businessmen without taking out new rural cooperative medical insurance,taking up transportation distance less than 80 km,and subjecting to killip grade Ⅰ had a higher proportion of individuals of this kind taking self-transportation (P < 0.05).Conclusion Mode of transportation is an important factor that affects the time extended to get emergency intervention.Education level,occupation,medical insurance type,transportation distance,killip grade are associated with modes of transport.

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