1.Effect of polygonatum odoratum polysaccharide on acute kidney injury in mice induced by cisplatin and its ferroptosis mechanism
Fangyang JIANG ; Jing XIAO ; He CHANG ; Mingyang SUN ; Wenjing ZHANG ; Guangfu LYU ; He LIN ; Zhe LIN ; Xiaowei HUANG ; Yuchen WANG
Journal of Jilin University(Medicine Edition) 2024;50(5):1235-1242
Objective:To discuss the protective effect of polygonatum odoratum polysaccharide(POP)on the mice with cisplatin-induced acute kidney injury(AKI),and to clarify its possible mechanism.Methods:Forty male C57BL/6 mice were randomly divided into control group,model group,POP group,and ferroptosis inducer Erastin combined with POP(Erastin+POP)group,and there were 10 mice in each group.The mice in POP group and Erastin+POP group were given intragastric administration of POP(400 mg·kg-1),and on the 7th day,the mice in model group,POP group,and Erastin+POP group were intraperitoneally injected with cisplatin(20 mg·kg-1)to establish the AKI models,the mice in control group were injected with the same volume of normal saline,and the mice in Erastin+POP group were intraperitoneally injected with Erastin(40 mg·kg-1)one day in advance(on the 6th day of the experiment).After 9 d,the mice were killed and the serum and kidney tissue were collected,and the levels of serum creatinine(Scr)and blood urea nitrogen(BUN)and the levels of malondialdehyde(MDA)and glutathione(GSH)in kidney tissue of the mice in various groups were detected by kit;HE staining was used to observe the pathomorphology of kidney tissue of the mice in various groups;the expression levels of ferroptosis suppressor protein 1(FSP1),ferritin heavy chain 1(FTH1),and glutathione peroxidase 4(GPX4)proteins in kidney tissue of the mice in various groups were detected by immunohistochemistry;Western blotting method was used to detect the expression levels of nuclear factor-E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins in kidney tissue of the mice in various groups.Results:Compared with control group,the levels of Scr and BUN of the mice in model group were significantly increased(P<0.01),the level of MDA in kidney tissue was significantly increased(P<0.01),and the level of GSH was significantly decreased(P<0.01);most kidney tubules were dilated,the epithelial cells were swollen,the vacuolar degeneration and epithelial cells fell off,and the protein-like tubules could be seen in the lumen;the expression levels of FSP1,FTH1,GPX4,Nrf2,and HO-1 proteins in kidney tissue were decreased significantly(P<0.05 or P<0.01).Compared with model group,the levels of Scr and BUN of the mice in POP group were significantly decreased(P<0.01),the level of MDA in kidney tissue was significantly decreased(P<0.01),and the level of GSH was significantly increased(P<0.01);the dilatation of kidney tubular lumen,epithelial cell swelling,vacuolar degeneration,and epithelial cell exfoliation were decreased;the expression levels of FSP1,FTH1,GPX4,Nrf2,and HO-1 proteins in kidney tissue of the mice in POP group were significantly increased(P<0.05 or P<0.01).Compared with POP group,the levels of Scr and BUN of the mice in Erastin+POP group were significantly increased(P<0.01),the level of MDA in kidney tissue was increased(P<0.05),and the level of GSH was significantly decreased(P<0.01);the pathological injury of kidney tissue was aggravated obviously;the expression levels of FSP1,FTH1,GPX4,Nrf2,and HO-1 proteins in kidney tissue were significantly decreased(P<0.05 or P<0.01).Conclusion:POP can reduce the AKI in the mice induced by cisplatin,and its mechanism may be related to the inhibitory effect of POP on the ferroptosis induced by cisplatin.
2.TRIB3 promotes pulmonary fibrosis through inhibiting SLUG degradation by physically interacting with MDM2.
Xiaoxi LV ; Shanshan LIU ; Chang LIU ; Yunxuan LI ; Tingting ZHANG ; Jie QI ; Ke LI ; Fang HUA ; Bing CUI ; Xiaowei ZHANG ; Yuxin LIU ; Jiaojiao YU ; Jinmei YU ; Li LI ; Xia LI ; Zhigang YAO ; Bo HUANG
Acta Pharmaceutica Sinica B 2023;13(4):1631-1647
Pulmonary fibrosis (PF) is the pathological structure of incurable fibroproliferative lung diseases that are attributed to the repeated lung injury-caused failure of lung alveolar regeneration (LAR). Here, we report that repetitive lung damage results in a progressive accumulation of the transcriptional repressor SLUG in alveolar epithelial type II cells (AEC2s). The abnormal increased SLUG inhibits AEC2s from self-renewal and differentiation into alveolar epithelial type I cells (AEC1s). We found that the elevated SLUG represses the expression of the phosphate transporter SLC34A2 in AEC2s, which reduces intracellular phosphate and represses the phosphorylation of JNK and P38 MAPK, two critical kinases supporting LAR, leading to LAR failure. TRIB3, a stress sensor, interacts with the E3 ligase MDM2 to suppress SLUG degradation in AEC2s by impeding MDM2-catalyzed SLUG ubiquitination. Targeting SLUG degradation by disturbing the TRIB3/MDM2 interaction using a new synthetic staple peptide restores LAR capacity and exhibits potent therapeutic efficacy against experimental PF. Our study reveals a mechanism of the TRIB3-MDM2-SLUG-SLC34A2 axis causing the LAR failure in PF, which confers a potential strategy for treating patients with fibroproliferative lung diseases.
3.The association of hyponatremia with clinicopathological and prognostic characteristics of non-small cell lung cancer patients: A systematic review and meta-analysis
Xiaowei WANG ; Shuai CHANG ; Wenpeng SONG ; Guowei CHE
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(03):428-433
Objective To explore the association of pretreatment hyponatremia with clinicopathological and prognostic characteristics of non-small cell lung cancer (NSCLC) patients. Methods The PubMed, EMbase, Web of Science, VIP, CNKI and WanFang databases were searched from the inception to July 12, 2021 for relevant literatures. The quality of included studies was assessed by the Newcastle-Ottawa Scale (NOS) score. The relative risk (RR) and hazard ratio (HR) with 95% confidence interval (CI) were combined to assess the relationship between pretreatment hyponatremia and clinicopathological and prognostic characteristics. The prognostic indicators included the overall survival (OS) and progression-free survival (PFS). All statistical analysis was conducted by the STATA 15.0 software. Results A total of 10 high-quality studies (NOS score≥6 points) involving 10 045 patients were enrolled and all participants were from Asian or European regions. The pooled results demonstrated that male [RR=1.18, 95%CI (1.02, 1.36), P=0.026], non-adenocarcinoma [RR=0.86, 95%CI (0.81, 0.91), P<0.001] and TNM Ⅲ-Ⅳ stage [RR=1.17, 95%CI (1.12, 1.21), P<0.001] patients were more likely to experience hyponatremia. Besides, pretreatment hyponatremia was significantly related to worse OS [HR=1.83, 95%CI (1.53, 2.19), P<0.001] and PFS [HR=1.54, 95%CI (1.02, 2.34), P=0.040]. Pretreatment hyponatremia was a risk factor for poor prognosis of NSCLC patients. Conclusion Male, non-adenocarcinoma and advance stage NSCLC patients are more likely to experience hyponatremia. Meanwhile, the pretreatment sodium level can be applied as one of the prognostic evaluation indicators in NSCLC and patients with hyponatremia are more likely to have poor survival. However, more researches are still needed to verify above findings.
4.The cell cycle inhibitor P21 promotes the development of pulmonary fibrosis by suppressing lung alveolar regeneration.
Xiaoxi LV ; Chang LIU ; Shanshan LIU ; Yunxuan LI ; Wanyu WANG ; Ke LI ; Fang HUA ; Bing CUI ; Xiaowei ZHANG ; Jiaojiao YU ; Jinmei YU ; ZhuoWei HU
Acta Pharmaceutica Sinica B 2022;12(2):735-746
The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.
5.Function and mechanism of ferroptosis in the radiation resistance of colorectal tumor-repopulating cells
CHANG Yuhan ; Ge Yutong ; HA Wentao ; WEI Xiaowei ; GONG Yongling
Chinese Journal of Cancer Biotherapy 2022;29(5):426-433
[Abstract] Objective: To investigate the function and mechanism of ferroptosis in the radiation resistance of colorectal tumor-repopulating cells. Methods: Human colorectal tumor cells HCT116 (defined as Control cells) were cultured in two-dimensional normal conditions, and tumor regenerative cells with high tumorigenicity (defined as TRCs) were cultured and screened in three-dimensional fibrin soft gels by the mechanical force method. Both the control group and TRC group cells were exposed to X-rays with different doses (2, 4, 6, 8 Gy) and MTS and the clone formation assay were used tomeasure the cell viability rate and proliferation ability. After the Control cells and TRCs were treated with ferroptosis inducer (Erastin) and X-rays respectively, they were stained with C11-BODIPY reagent, and the lipid peroxidation level of the cells was observed and determined by confocal microscopy and flow cytometry. qPCR was used to determine the effects of Erastin and X-rays treatments on the expressions of ferroptosis-related genes glutathione peroxidase 4 (GPX4) and acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) in the Control cells and TRCs; WB assay was performed to determine the effects on the expressions of ferroptosis-related proteins GPX4 and ACSL4. Results: Colorectal TRCs with high stemness were cultured and screened out from soft fibrin gels. After irradiation with different doses (2, 4, 6, 8 Gy) of X-rays, the viability rate, the clone sizeand the number of clones in the control group were significantly lower than those in the TRC group (all P<0.05). After the cells in the control group were irradiated with different doses of X-rays (4, 8 Gy) and treated with Erastin, the lipid peroxidation level of the cells in the X-ray treated group was significantly higher than that in the untreated group (P<0.05). The lipid peroxidation level of the cells in the Erastin-treated group was significantly higher than that in the DMSO-treated group (P<0.05). There was no statistical difference among all treatment subgroups in the TRC group (all P>0.05). The mechanism study indicated that compared with those in control cells, GPX4 and ACSL4 in TRCs under ferroptosis-inducing conditions (X-ray radiation and Erastin treatment) presented expressions that contributed more to radiation resistance, i.e., continued upregulation of GPX4 and downregulation of ACSL4 and their expressions were dependent on the doses of Erastin. Conclusion: Colorectal TRCs may resist ferroptosis through a high expression of GPX4 and a low expression of ACSL4, which in turn induces radiation resistance.
6.Status of nutritional knowledge, attitude and practice of tumor nursing staff and its influencing factors
Hu CHANG ; Xiaowei ZHANG ; Ruixian HE
Chinese Journal of Modern Nursing 2022;28(8):1061-1065
Objective:To explore status of nutritional knowledge, attitude and practice of tumor nursing staff and analyze the influencing factors.Methods:Using the convenient sampling method, a total of 800 nurses from Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College were selected as the research objects from January to February 2021. General data questionnaire, Nutrition Knowledge, Attitude and Practice Questionnaire for Tumor Nursing Staff and Nutrition Knowledge Acquisition Way Questionnaire for Tumor Nursing Staff were used to investigate. A total of 800 questionnaires were sent out and 797 were valid.Results:For 797 tumor nursing staff, the total score of Nutrition Knowledge, Attitude and Practice Questionnaire for Tumor Nursing Staff was (63.50±14.87) . The passing rate was 62.0% and the excellent rate was 13.8%. The results of multivariate analysis showed that professional title, educational background and department were the influencing factors of nutrition knowledge, attitude and practice of tumor nurses ( P<0.05) . Conclusions:Tumor nursing staff have positive attitudes and practice towards nutrition therapy, but their knowledge of nutrition needs to be strengthened. It is necessary to carry out nutrition-related training based on influencing factors.
7.Status quo and influencing factors of professional identity of nursing undergraduates in Beijing
Huiling WU ; Liping WU ; Chang ZHANG ; Xiaowei SHAO ; Litong LIU
Chinese Journal of Modern Nursing 2022;28(14):1951-1955
Objective:To investigate the status quo of professional identity of nursing undergraduates in Beijing and analyze its influencing factors and to provide basis for carrying out professional identity education of nursing undergraduates.Methods:Using the convenient sampling method, a total of 726 nursing undergraduates from four undergraduate colleges in Beijing from June to September 2020 were selected as research objects. General information questionnaire, Professional Identity Questionnaire for Nurse Students (PIQNS) and Professional Self-efficacy Questionnaire for Nurse Students (PSQNS) were used to investigate them. A total of 726 questionnaires were distributed and 615 valid questionnaires were recovered.Results:The total scores of PIQNS and PSQNS among 615 nursing undergraduates in Beijing were respectively 55.00 (36.00, 66.00) and 86.00 (60.00, 101.00) . There was a positive correlation between PIQNS total score and PSQNS total score of nursing undergraduates ( r=0.928, P<0.01) . The results of multiple linear regression analysis showed that gender, whether there was a class tenure, whether he was an only child, reasons for attending nursing major and whether he had clinical practice or internship experience were the influencing factors of professional identity of nursing undergraduates in Beijing ( P<0.01) , which could explain 17.6% of the total variation. Conclusions:The professional identity of nursing undergraduates in Beijing is at the medium level and still needs to be improved. Nursing educators should pay attention to the emotional and psychological status of nursing undergraduates and take appropriate measures to provide vocational education for nursing undergraduates, so as to further improve their professional identity.
8.TRIB3‒GSK-3
Shanshan LIU ; Xiaoxi LV ; Xupeng WEI ; Chang LIU ; Qiao LI ; Jiali MIN ; Fang HUA ; Xiaowei ZHANG ; Ke LI ; Pingping LI ; Yang XIAO ; Zhuowei HU ; Bing CUI
Acta Pharmaceutica Sinica B 2021;11(10):3105-3119
Pulmonary fibrosis (PF) is a chronic, progressive, fatal interstitial lung disease with limited available therapeutic strategies. We recently reported that the protein kinase glycogen synthase kinase-3
9.Repair experience of skin necrosis after penile thickening with acellular dermal matrix patch
Haichen SONG ; Xiaowei WU ; Wenchuan CHANG
Chinese Journal of Urology 2021;42(11):864-866
A serious complication of penile girth enhancement with acellular dermal matrix(ADM) patch is large area penile skin necrosis. Since the penile skin has characteristics such as thin, elasticity, pliability, and durability to withstand erection and friction, the repair surgery is often difficult to achieve good results. Furthermore, the implantation of ADM patch increases the difficulty of surgery. From March 2014 to August 2019, a total of 13 patients with skin necrosis after penile girth enhancement with ADM patch were treated in our center.The debridement and change dressing, according to the condition of the necrotic skin of penis, were performed in all patients. 7 patients used the repairing method of scrotal skin flap via one side scrotal artery, 6 patients used the repairing method of full thickness skin graft. The penile function was not affected with 6 to 12 months′ follow-up after surgery and the curative effect was satisfactory.
10.Correlation analysis of adolescent depression, suicidal intention and parental rearing style
Suping LI ; Linbo LI ; Xiaowei CHANG
Chinese Journal of Modern Nursing 2021;27(20):2753-2757
Objective:To understand the status quo of adolescent depression, suicidal intention and parental rearing style and to analyze the correlations of the three.Methods:Using the convenient sampling method, a total of 175 adolescent depressive patients who were hospitalized in the Department of Mental Health in First Hospital of Shanxi Medical University from October 2019 to November 2020 were selected for questionnaire survey. The Hamilton Depression Scale (HAMD) , the Scale of Suicide Ideation (SSI) and Egma Minnen av Bardndosnauppforstran (EMBU) were used to understand the current status of adolescent depression, suicidal intentions and parental rearing style. Pearson correlation analysis method was used to analyze the correlation between adolescent depression, suicidal intention and parental rearing style. In this study, a total of 175 questionnaires were distributed and 172 valid questionnaires were returned. The effective recovery rate was 98.3%.Results:The scores of HAMD, SSI and EMBU in 172 patients were (22.72±7.90) , (20.19±8.45) and (205.51±21.91) , respectively. Adolescent depression was positively correlated with paternal overprotection, maternal overprotection intervention and maternal severe punishment ( P<0.05) , and negatively correlated with paternal (maternal) warm understanding ( P<0.01) . Adolescent suicide intention was negatively correlated with parental (maternal) warm understanding ( P<0.01) , and positively correlated with paternal preference for subjects, maternal severe punishment and maternal overprotective interference ( P<0.05) . Conclusions:Giving positive and correct guidance to adolescent parents, digging out the causes of negative parenting styles and helping parents form positive parenting styles are of great significance for improving adolescent depression and suicidal intention.

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