Objective:To investigate the inhibitory effect of astragaloside Ⅳ(AS-Ⅳ)on cisplatin(CDDP)-induced liver injury in the mice,and to elucidate its possible mechanism.Methods:Forty male C57BL/6 mice with body weights of 18-22 g were randomly divided into control group,model group,AS-Ⅳ group and adenosine 5'-monophosphate-activated protein kinase(AMPK)inhibitor(Compound C)+AS-Ⅳ group.The mice in control group and model group were gavaged with the same volume of normal saline,and the drug was administered continuously for 9 d.The mice in AS-Ⅳ group and Compound C+AS-Ⅳ group were given AS-Ⅳ aqueous solution(150 mg·kg-1·d-1),respectively.On the 6th day of experiment,the mice in Compound C+AS-Ⅳ group were intraperitoneally injected with Compound C(20 mg·kg-1),and on the 7th day,except for control group,the mice in other groups were intraperitoneally injected with 20 mg·kg-1 CDDP to establish the mouse liver injury models,and the mice were sacrificed 48 h later.Serum and liver tissues were collected,and the levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)in the serum of the mice,as well as the activities of superoxide dismutase(SOD)and catalase(CAT)and the levels of malondialdehyde(MDA)in the liver tissue of the mice in various groups were detected by kits.The pathomorphology of liver tissue of the mice in various groups were detected by HE staining.The expression levels of glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1)and ferroptosis inhibitory protein 1(FSP1)proteins in liver tissue of the mice in various groups were detected by immunohistochemical staining,and the expression levels of nuclear factor-E2-related factor 2(Nrf2),heme oxygenase-1(HO-1)and AMPK proteins in liver tissue of the mice in various groups were detected by Western blotting method.Results:Compared with control group,the levels of AST and ALT in serum of the mice in model group were increased(P＜0.01),the activities of SOD and CAT in the liver tissue were significantly decreased(P＜0.01),and the MDA level was increased(P＜0.01);compared with model group,the levels of AST and ALT in serum of the mice in AS-Ⅳ group were decreased(P＜0.01),the MDA level in the liver tissue was decreased(P＜0.01),and the activities of SOD and CAT were increased(P＜0.01);compared with AS-Ⅳ group(P＜0.01),the levels of AST and ALT in serum of the mice in Compound C+AS-Ⅳ group were increased(P＜0.01),the level of MDA in liver tissue was increased(P＜0.05),and the activities SOD and CAT were decreased(P＜0.01).The HE staining results showed that compared with control group,the liver damage degree of the mice in model group was enhanced,the hepatocyte arrangement was disordered,and some hepatocyte edema were increased;compared with model group,the liver morphology of the mice in AS-Ⅳ group returned to normal;compared with AS-Ⅳ group,the hepatocyte arrangement of the mice in Compound C+AS-Ⅳ group was disordered and the edges were blurred.The immunohistochemistry results showed that compared with control group,the expression levels of GPX4,FTH1 and FSP1 proteins in liver tissue of the mice in model group were decreased(P＜0.05);compared with model group,the expression levels of GPX4,FTH1 and FSP1 proteins in liver tissue of the mice in AS-Ⅳ group were increased(P＜0.05);compared with AS-Ⅳ group,the expression levels of GPX4,FTH1 and FSP1 proteins in liver tissue of the mice in Compound C+AS-Ⅳ group were decreased(P＜0.05 or P＜0.01).The Western blotting results showed that compared with control group,the expression levels of Nrf2,HO-1 and AMPK proteins in liver tissue of the mice in model group were decreased(P＜0.01);compared with model group,the expression levels of Nrf2,HO-1 and AMPK proteins in liver tissue of the mice in AS-Ⅳgroup were increased(P＜0.01);compared with AS-Ⅳ group,the expression levels of Nrf2,HO-1 and AMPK proteins in liver tissue of the mice in Compound C+AS-Ⅳ group were decreased(P＜0.01).Conclusion:AS-Ⅳ can alleviate the CDDP-induced liver injury,and its mechanism may be related to the regulation of AMPK/Nrf2/HO-1 signal pathway and ferroptosis by AS-Ⅳ.

Objective:To explore the diagnostic value of blood flow parameters of carotid ultrasound combined with serum Sortilin and paraoxonase-1 (PON-1) for stability of carotid atherosclerotic plaque (CAP). Methods:A total of 100 CAP patients who admitted to Rugao Hospital of Traditional Chinese Medicine from January 2021 to December 2023 were selected,and they were divided into a stable plaque group (n=54) and a unstable plaque group (n=46). Enzyme linked immunosorbent assay (ELISA) was adopted to determine the expression levels of serum Sortilin and PON-1 of patients in two groups. Multi factor logistic regression was implemented to analyze the influencing factors on CAP stability. The receiver operating characteristic (ROC) curves were drawn to analyze the diagnostic efficiency of blood flow parameters of carotid ultrasound combined with Sortilin and PON-1 on CAP stability. Results:Compared with the end diastolic blood flow velocity (EDV) and intima-media thickness (IMT) of stable plaque group,unstable plaque group showed increased EDV and IMT,and decreased PSV,and the differences were significant (t=7.536,4.680,5.487,P<0.05),respectively. Compared with stable plaque group,the serum Sortilin level in unstable plaque group significantly increased,while the PON-1 level significantly decreased,and the differences of them were significant (t=8.362,5.581,P<0.05),respectively. Multivariate logistic analysis found that Sortilin was a risk factor that affected CAP stability (OR=3.165,P<0.05),while PON-1 was a protective factor that affected CAP stability (OR=0.765,P<0.05). ROC curve analysis indicated that the area under curve (AUC) values of single Sortilin,PON-1,EDV,IMT,PSV,and the combination of them were respectively 0.788 (95％CI:0.695-0.864),0.814 (95％CI:0.724-0.885),0.847 (95％ CI:0.761-0.911),0.767 (95％ CI:0.672-0.846),0.707 (95％ CI:0.607-0.793) and 0.963 (95％ CI:0.839-0.907). The AUC value of the combination of above 5 indicators was highest,which was better than that of each single indicator,and its sensitivity and specificity were respectively 95.65％ and 83.33％. Conclusion:The EDV,IMT and PSV of blood flow parameters of ultrasound can provide CAP information of morphology and hemodynamics,and serum Sortilin level and PON-1 level can reflect the biological processes of formation and development of CAP. The combined detection of the five indicators can better diagnose CAP stability.

Objective:To explore the diagnostic value of blood flow parameters of carotid ultrasound combined with serum Sortilin and paraoxonase-1 (PON-1) for stability of carotid atherosclerotic plaque (CAP). Methods:A total of 100 CAP patients who admitted to Rugao Hospital of Traditional Chinese Medicine from January 2021 to December 2023 were selected,and they were divided into a stable plaque group (n=54) and a unstable plaque group (n=46). Enzyme linked immunosorbent assay (ELISA) was adopted to determine the expression levels of serum Sortilin and PON-1 of patients in two groups. Multi factor logistic regression was implemented to analyze the influencing factors on CAP stability. The receiver operating characteristic (ROC) curves were drawn to analyze the diagnostic efficiency of blood flow parameters of carotid ultrasound combined with Sortilin and PON-1 on CAP stability. Results:Compared with the end diastolic blood flow velocity (EDV) and intima-media thickness (IMT) of stable plaque group,unstable plaque group showed increased EDV and IMT,and decreased PSV,and the differences were significant (t=7.536,4.680,5.487,P<0.05),respectively. Compared with stable plaque group,the serum Sortilin level in unstable plaque group significantly increased,while the PON-1 level significantly decreased,and the differences of them were significant (t=8.362,5.581,P<0.05),respectively. Multivariate logistic analysis found that Sortilin was a risk factor that affected CAP stability (OR=3.165,P<0.05),while PON-1 was a protective factor that affected CAP stability (OR=0.765,P<0.05). ROC curve analysis indicated that the area under curve (AUC) values of single Sortilin,PON-1,EDV,IMT,PSV,and the combination of them were respectively 0.788 (95％CI:0.695-0.864),0.814 (95％CI:0.724-0.885),0.847 (95％ CI:0.761-0.911),0.767 (95％ CI:0.672-0.846),0.707 (95％ CI:0.607-0.793) and 0.963 (95％ CI:0.839-0.907). The AUC value of the combination of above 5 indicators was highest,which was better than that of each single indicator,and its sensitivity and specificity were respectively 95.65％ and 83.33％. Conclusion:The EDV,IMT and PSV of blood flow parameters of ultrasound can provide CAP information of morphology and hemodynamics,and serum Sortilin level and PON-1 level can reflect the biological processes of formation and development of CAP. The combined detection of the five indicators can better diagnose CAP stability.

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.

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.

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.

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.

[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.

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.

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.