1.Cordycepin attenuates gentamicin-induced kidney injury by inhibiting oxidative stress and ferroptosis
Lin YUE ; Cao-mei XU ; Min-yan QIAN ; Wen-ting ZHANG ; Xiao ZHENG ; Lu-jun CHEN ; Jing-ting JIANG ; Nan HU
Chinese Pharmacological Bulletin 2025;41(1):65-70
Aim To investigate the effect of cordycepin(COR)on gentamicin(GEN)-induced nephrotoxicity and the molecular mechanism of inhibiting oxidative stress and ferroptosis induced by GEN.Methods The oral SD rats were divided into a control group,GEN group,and GEN+COR group.Following the success-ful setting up of the animal model,the serum creatinine(CR)and urea nitrogen(BUN)levels of rats were measured,and renal tissue injury was assessed using HE staining.In addition,the contents of malondialde-hyde and glutathione in kidney tissues of SD rats in each group were detected,and the expressions of fer-roptosis markers GPX4 and SLC7A11 were analyzed by Western blot.Results Compared with the control group,CR and BUN in GEN-stimulated group signifi-cantly increased(P<0.01),and the level of CR and BUN was effectively reduced after 50 mg·kg-1 COR oral administration.HE results also showed that COR could alleviate the kidney tissue damage caused by GEN.COR could reverse the increase of malondialde-hyde level and the decrease of glutathione level caused by GEN in rat kidney tissue,and COR could restore the decrease of GPX4 and SLC7A11 protein levels induced by GEN.Conclusion COR can reduce GEN-induced kidney injury by inhibiting oxidative stress and ferrop-tosis.
2.Study on synergistic promotion of ferroptosis in human hypertrophic scar fibroblasts by erastin combined with shikonin
Jian-jun WANG ; Yan-hua WANG ; Yu-ting TANG ; Jing-yi ZHANG ; Fang MA ; Xi HE ; Hui-xia YANG ; Qi-peng ZHAO ; Zhi-gang BAI ; Yin-ju HAO ; Gui-zhong LI ; Yi-deng JIANG ; Jiang-yong SHEN
Chinese Pharmacological Bulletin 2025;41(2):268-276
Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50%).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P<0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P<0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P<0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P<0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.
3.Predicting axillary lymph node metastasis in invasive breast cancer using machine learning models based on serum biomarkers and other clinical features
Yilihamu YIPALA ; Wang LEI ; Ma TAO ; Gao CHUNJIE ; Liu JING ; Zhao TING ; Wang YAN
Chinese Journal of Clinical Oncology 2025;52(10):507-514
Objective:Serum tumor markers(STMs)are important indicators associated with metastasis in patients with breast cancer(BC).This study focuses on predicting the risk of axillary lymph node metastasis(ALNM)in patients with invasive BC in Xinjiang by combining STMs and clinicopathological factors.Methods:Data from 3,360 patients diagnosed with invasive BC and treated at the Affiliated Cancer Hospital of Xinjiang Medical University between 2015 and 2019 were analyzed,focusing on 11 relevant demographic and clinical factors.Five ma-chine learning(ML)algorithms were used to develop predictive models for ALNM.Their performance was compared using metrics such as area under the curve(AUC),accuracy,Kappa value,and Brier score.The best-performing model was then compared with a nomogram based on Logistic regression(LR)to determine the final model.Shapley additive explanations(SHAP)values were used to rank the importance of factors contributing to ALNM.Results:Of the 3,266 patients studied,1,368(41.89%)developed ALNM.Among the five constructed ML models,eXtreme gradient boosting(XGBoost)demonstrated the best predictive performance with an AUC of 0.768,an accuracy of 0.735,and a Kappa value of 0.450.In both the training and validation sets,the XGBoost model outperformed the LR-based nomogram(training set AUC and Brier score:0.822(0.810~0.820)vs.0.742(0.721~0.763),0.170(0.163~0.177)vs.0.197(0.189~0.204);validation set AUC and Brier score:0.769(0.740~0.770)vs.0.747(0.716~0.779),0.190(0.178~0.202)vs.0.195(0.189~0.204)).Therefore,XGBoost was selec-ted as the final predictive model.SHAP analysis identified T stage,age,molecular subtype,and CEA level as the four most influential factors for ALNM prediction.Conclusions:The XGBoost model effectively predicts the risk of ALNM in patients with invasive BC based on STMs and clinicopathological features,outperforming traditional nomograms.SHAP analysis highlighted T stage as the most critical factor influencing ALNM.
4.Predicting axillary lymph node metastasis in invasive breast cancer using machine learning models based on serum biomarkers and other clinical features
Yilihamu YIPALA ; Wang LEI ; Ma TAO ; Gao CHUNJIE ; Liu JING ; Zhao TING ; Wang YAN
Chinese Journal of Clinical Oncology 2025;52(10):507-514
Objective:Serum tumor markers(STMs)are important indicators associated with metastasis in patients with breast cancer(BC).This study focuses on predicting the risk of axillary lymph node metastasis(ALNM)in patients with invasive BC in Xinjiang by combining STMs and clinicopathological factors.Methods:Data from 3,360 patients diagnosed with invasive BC and treated at the Affiliated Cancer Hospital of Xinjiang Medical University between 2015 and 2019 were analyzed,focusing on 11 relevant demographic and clinical factors.Five ma-chine learning(ML)algorithms were used to develop predictive models for ALNM.Their performance was compared using metrics such as area under the curve(AUC),accuracy,Kappa value,and Brier score.The best-performing model was then compared with a nomogram based on Logistic regression(LR)to determine the final model.Shapley additive explanations(SHAP)values were used to rank the importance of factors contributing to ALNM.Results:Of the 3,266 patients studied,1,368(41.89%)developed ALNM.Among the five constructed ML models,eXtreme gradient boosting(XGBoost)demonstrated the best predictive performance with an AUC of 0.768,an accuracy of 0.735,and a Kappa value of 0.450.In both the training and validation sets,the XGBoost model outperformed the LR-based nomogram(training set AUC and Brier score:0.822(0.810~0.820)vs.0.742(0.721~0.763),0.170(0.163~0.177)vs.0.197(0.189~0.204);validation set AUC and Brier score:0.769(0.740~0.770)vs.0.747(0.716~0.779),0.190(0.178~0.202)vs.0.195(0.189~0.204)).Therefore,XGBoost was selec-ted as the final predictive model.SHAP analysis identified T stage,age,molecular subtype,and CEA level as the four most influential factors for ALNM prediction.Conclusions:The XGBoost model effectively predicts the risk of ALNM in patients with invasive BC based on STMs and clinicopathological features,outperforming traditional nomograms.SHAP analysis highlighted T stage as the most critical factor influencing ALNM.
5.Construction of a nursing follow-up checklist for patients undergoing autologous hematopoietic stem cell transplantation
Ting WANG ; Jiating WANG ; Aiyun JIN ; Xiaming ZHU ; Yun FANG ; Jing WANG ; Fei TIAN ; Yiqin PU ; Ying WAN ; Jin HE ; Xia YAN
Chinese Journal of Nursing 2025;60(8):914-920
Objective To construct a nursing follow-up checklist for patients undergoing autologous hematopoietic stem cell transplantation,providing a basis for postoperative follow-up care.Methods Using evidence-based methods,the literature from major guide websites and databases using Chinese and English search terms was retrieved,and their quality was evaluated.The relevant items were extracted,and a first draft was formed.15 experts were selected in relevant fields from 14 tertiary hospitals in 13 provinces,cities,and autonomous regions across the country for Delphi inquiry.The nursing follow-up checklist was revised again based on expert opinions and clinical practice.The nursing follow-up checklist was initially applied and then revised again to form the final draft.Results 15 experts include 12 undergraduate and 3 master's degree holders.The positivity coefficients of the 2 rounds of inquiry were 100%;the authority coefficients of the experts were 0.815;the Kendall coefficients were 0.119 and 0.144,respectively;the differences were statistically significant(P<0.001).The final nursing follow-up checklist was formed,which includes 6 primary indicators,including physiological status,psychological status,social and family support,living conditions,disease knowledge,and laboratory tests.19 patients(95%)found the follow-up content to be comprehensive.The follow-up nurses's satisfaction rate exceeded 85%.There were 27 secondary indicators and 61 tertiary indicators,with coefficients of variation of all indicators less than 0.25.Conclusion The nursing follow-up checklist is scientific,reliable,and practical,which can provide a basis for clinical nursing staff to follow up and comprehensively manage patients after autologous hematopoietic stem cell transplantation.
6.Relationship between cognitive function and sleep quality in Alzheimer's disease
Yan YAN ; Junlei ZHANG ; Jingnian NI ; Ting LI ; Jing SHI ; Jinzhou TIAN ; Mingqing WEI
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(4):440-444
Objective To investigate the relationship between cognitive function and sleep quality in patients with Alzheimer's disease(AD).Methods A case-control trial was conducted on 151 patients admitted to our department from May 2024 to December 2024.The patients with mild-to-moderate AD were assigned into the AD group(59 cases),and the cognitively normal patients in-to the control group(92 cases).All patients received neuropsychological assessment and sleep quality evaluation,including mini-mental state examination(MMSE),Montreal cognitive assess-ment(MoCA)and Pittsburgh sleep quality index(PSQI).The general clinical data and sleep qual-ity were compared between the two groups.Spearman correlation analysis was applied to analyze the relationship between cognitive function and sleep quality in the AD patients.Results The education level,MMSE score,MoCA score,instant story recall(ISR)score,delayed story recall(DSR)score,clock dawning test(CDT)score and Boston naming test score were significantly lower,while the activity of daily living(ADL)score was obviously higher in the AD group than the cognitively normal group(P<0.05,P<0.01).The AD patients had notably higher total score of PSQI and scores of sleep efficiency,nocturnal sleep disturbance and daytime dysfunction than the cognitively normal patients(P<0.05,P<0.01).In the AD patients,the total sleep time was positively correlated with the DSR score and the CDT score(r=0.300,P=0.021;r=0.308,P=0.018);hypnotic medication was negatively correlated with MMSE score,ISR score,and DSR score,and positively with ADL score(r=-0.320,P=0.013;r=-0.400,P=0.002;r=-0.331,P=0.010;r=0.355,P=0.006).Multiple linear regression analysis showed that benzodiazepines use and education level were independent influencing factors for cognitive function in the AD patients(P<0.05,P<0.01).Conclusion In AD patients,sleep quality is closely associated with cognitive function,as manifested by decreased sleep quality,reduced sleep efficiency,and worsened nocturnal sleep disturbances and daytime dysfunction.Administration of benzodiazepines may exacerbate cognitive impairment in AD patients.So,it is recommended that AD patients should be cautious about taking such drugs.
7.The role and research progress of m6A modification in sepsis and its induced multi-organ dysfunction disease
Lu-lu ZHANG ; Rui GONG ; Jin-yi ZHAO ; Fei MU ; Yan-ping YIN ; Wang-ting LI ; Ling-ling ZHENG ; Yu-ping TANG ; Jing-wen WANG
Chinese Pharmacological Bulletin 2025;41(3):421-427
Sepsis is a life-threatening organ dysfunction disease caused by a dysregulated host response to infection.It has com-plex pathophysiological changes,and in severe cases,it can rap-idly develop into septic shock and multiple organ dysfunction or multiple organ failure.At present,the pathological mechanism of sepsis and its induced organ dysfunction is complex and the in-fluencing factors are numerous.So far,there is still a lack of specific and effective treatment strategies.RNA modify-N6-methyladenosine(m6 A)is one of the most common post-tran-scriptional modifications on eukaryotic RNAs.It is involved in the regulation of the occurrence and development of a variety of inflammatory diseases,including sepsis,and even multiple organ dysfunction induced by sepsis by affecting the metabolism of RNAs.It includes cardiac dysfunction,acute lung injury(ALI)and acute kidney injury(AKI).Therefore,this article will dis-cuss the effect of m6A modification on the function of immune cells,and its important role in sepsis and its induced multiple or-gan dysfunction diseases by regulating inflammatory signals,py-roptosis,mitochondrial damage and ferroptosis.This will provide new therapeutic targets and strategies for the clinical prevention and treatment of sepsis and its induced multiple organ dysfunc-tion diseases.
8.Effect of salidroside combined with rosavin on ischemic brain injury in rats
Wen-fang LAI ; Yu-ting JIANG ; Jing-quan CHEN ; Xue-rui ZHENG ; Hui-ling WU ; Qing-qing WU ; Yan CHEN ; Ya LIN
Chinese Pharmacological Bulletin 2025;41(11):2058-2065
Aim To study the mechanism of salidro-side combined with rosavin in rats with ischemic stroke.Methods The MCAO rats was established by using thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside com-bined with rosavin group,and positive control group;the drug was given continuously for seven days.Western blot was used to detect apoptosis indicators.Proteomics was used to analyse differential proteins(DEPs).STEP receptor inhibitor was injected into the lateral ventricles,the rats were administered for seven days,then the apoptosis indicators were detected.Re-sults Salidroside combined with rosavin could reduce neurological function scores in MCAO rats and inhibit cell apoptosis.Quantitative proteomics identified 496 DEPs in brain tissue and discovered core proteins STEP,p38,and CRTC1.Salidroside combined with rosavin could promote the STEP and CRTC1 while in-hibiting p38 protein.After treatment with STEP inhibi-tor,those effects were reversed.Conclusion Salidro-side combined with rosavin can inhibit cell apoptosis in MCAO rats,which is closely related to the regulation of the STEP/p38/CRTC1 signaling pathway.
9.Effect of salidroside combined with rosavin on ischemic brain injury in rats
Wen-fang LAI ; Yu-ting JIANG ; Jing-quan CHEN ; Xue-rui ZHENG ; Hui-ling WU ; Qing-qing WU ; Yan CHEN ; Ya LIN
Chinese Pharmacological Bulletin 2025;41(11):2058-2065
Aim To study the mechanism of salidro-side combined with rosavin in rats with ischemic stroke.Methods The MCAO rats was established by using thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside com-bined with rosavin group,and positive control group;the drug was given continuously for seven days.Western blot was used to detect apoptosis indicators.Proteomics was used to analyse differential proteins(DEPs).STEP receptor inhibitor was injected into the lateral ventricles,the rats were administered for seven days,then the apoptosis indicators were detected.Re-sults Salidroside combined with rosavin could reduce neurological function scores in MCAO rats and inhibit cell apoptosis.Quantitative proteomics identified 496 DEPs in brain tissue and discovered core proteins STEP,p38,and CRTC1.Salidroside combined with rosavin could promote the STEP and CRTC1 while in-hibiting p38 protein.After treatment with STEP inhibi-tor,those effects were reversed.Conclusion Salidro-side combined with rosavin can inhibit cell apoptosis in MCAO rats,which is closely related to the regulation of the STEP/p38/CRTC1 signaling pathway.
10.Investigation of effects of petroleum ether fraction from Derris eriocarpa on glucose and lipid metabolism in a mouse model of metabolic syndrome via ATF3/HNF4ɑ/CYP7A1 pathway
Jing YAN ; Jie WENG ; Xuan ZHANG ; Xue LI ; Chao-nan KONG ; Hong-cun LIU ; Li-fang YANG ; Ming-guo JIANG ; Qiu-yan LIANG ; Li-ting HE
Chinese Traditional Patent Medicine 2025;47(9):2902-2911
AIM To investigate effects of petroleum ether fraction from Derris eriocarpa How on glucose and lipid metabolism in a mouse model of metabolic syndrome(MS).METHODS KM mice were fed a high-fat diet and administered streptozotocin intraperitoneally to establish MS models.The MS mice were then randomly assigned to the model group,the metformin hydrochloride group,the lovastatin group,the ursolic acid group,and the high-,medium-and low-dose D.eriocarpa petroleum ether fraction groups,with 10 mice in each group.Ten additional mice maitained on a normal diet served as the normal control group.After 4 weeks of intragastric administration,glucose and lipid metabolism indicators were measured.Hepatic pathological changes were assessed using HE staining and oil red O staining.Liver tissue mRNA expressions of ATF3,PEPCK,FXR,CYP7A1,HNF4ɑ,CYP8B1 and SRB1 were quantified by RT-qPCR.Hepatic protein expressions of ATF3,HNF4ɑ,PEPCK,FXR and CYP7A1 was analyzed by Western blot in MS mice.RESULTS Compared to the model group,the high-dose D.eriocarpa petroleum ether fraction group exhibited significant glucose tolerance improvement(reduced OGTT-AUC,P<0.01);favorable serum lipid modulation in terms of increased HDL-C levels(P<0.01)and decreased TG,TC,LDL-C(P<0.01);reduced renal biomarkers(BUN,SCR)and hepatotoxic indicators of TBA,AST and ALT activities(P<0.01);alleviated hepatic lipid accumulation and histopathological damage;downregulated mRNA and protein expressions of ATF3,HNF4ɑ and PEPCK,as well as CYP8B1 mRNA expression(P<0.01);and upregulated mRNA and protein expressions of FXR and CYP7A1,along with SRB1 mRNA expression(P<0.01).CONCLUSION D.eriocarpa petroleum ether fraction ameliorates glucose and lipid metabolism dysregulation in MS mice by modulating the ATF3/HNF4ɑ/CYP7A1 signaling pathway,consequently eliciting hypoglycemic,hypolipidemic,hepatoprotective and nephroprotective effects.

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