1.Effect of HSYA on LCN2-induced iron death of HT22 cells and its mechanism based on SLC7A11/GPX4 signaling pathway
Meng-wei RONG ; Cun-yan DAN ; Tian-qing XIA ; Yi YANG ; Xiu LOU ; Chen-xiang JI ; Bao-guo XIAO ; Cun-gen MA ; Li-juan SONG
Chinese Pharmacological Bulletin 2025;41(11):2097-2105
Aim To explore the effect of hydroxysafflor yellow A(HSYA)on lipocalin 2(LCN2)-induced fer-roptosis in HT22 cells and the related mechanism.Methods Thirty male Sprague-Dawley(SD)rats were used to establish the middle cerebral artery occlu-sion/reperfusion(MCAO/R)model by the suture method.The rats were randomly divided into the Sham group,the MCAO/R group,and the MCAO/R+HSYA group.The infarct area was measured by TTC staining,and the degree of neurological deficit was evaluated by the Z-Longa scoring method.The expressions of LCN2 and 24P3R in brain tissues were detected by Western blot.LCN2 protein was added to HT-22 cells,and the cells were divided into the normal group,the LCN2 group,and the LCN2+HSYA group.The optimal con-centration of LCN2-induced neuronal ferroptosis was screened by LDH assay and Western blot,and the ex-pression levels of ferritin,FPN1,GPX4,SLC7A11,COX2,and 24P3R were detected.LCN2 was knocked down by siRNA transfection,and the expressions of GPX4 and ferritin were detected.The contents of glu-tathione(GSH),malondialdehyde(MDA),GPX4,and Fe2+were determined by colorimetry,and the expres-sion of GPX4 was detected by immunofluorescence.The binding force between HSYA and LCN2 was ana-lyzed by molecular docking technology.Results Ani-mal experiments showed that HSYA could reduce the cerebral infarction area and decrease the neurological function score of MCAO/R rats.Compared with the sham group,the levels of LCN2 and 24P3R increased in the MCAO/R group,while HSYA inhibited their ex-pressions.Cell experiments showed that the optimal concentration of LCN2 to induce ferroptosis in HT22 cells was 2 μmol·L-1.After knocking down LCN2 by siRNA transfection,compared with the LCN2 group,the expression levels of GPX4 and ferritin in the siLCN2 group increased significantly.Compared with the nor-mal group,the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH in the LCN2 group decreased signifi-cantly,while the concentration of Fe2+,and the expres-sions of MDA,COX2,and 24P3R increased.HSYA could increase the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH,reduce the contents of Fe2+and MDA,and inhibit the expressions of COX2 and 24P3R.Molecular docking showed that the binding en-ergy between HSYA and LCN2 was-8.0 kJ·mol-1.Conclusion HSYA can inhibit LCN2-induced ferrop-tosis in HT22 cells through the SLC7A11/GPX4 signa-ling pathway.
2.Job Preferences of Centers for Disease Control and Prevention Workers: A Discrete Choice Experiment in China.
Yan GUO ; Han Lin NIE ; Hao CHEN ; Stephen NICHOLAS ; Elizabeth MAITLAND ; Si Si CHEN ; Lie Yu HUANG ; Xiu Min ZHANG ; Xue Feng SHI
Biomedical and Environmental Sciences 2025;38(6):740-750
OBJECTIVE:
This study explored the job choice preferences of Center for Disease Prevention and Control (CDC) workers to provide CDC management information and recommendations for optimizing employee retention and motivation policies.
METHODS:
A discrete choice experiment was conducted in nine provinces across China. Seven key attributes were identified to analyze the job preferences of CDC workers. Mixed logit models, latent class models, and policy simulation tools were used.
RESULTS:
A valid sample of 5,944 cases was included in the analysis. All seven attributes significantly influenced the job choices of CDC workers. Heterogeneity analyses identified two main groups based on different levels of preference for attribute utility. Income-prioritizers were concerned with income and opportunities for career development, whereas bianzhi-prioritizers were concerned with bianzhi and welfare benefits. The policy simulation analysis revealed that income-prioritizers had a relatively higher sensitivity to multiple job preference incentives.
CONCLUSION
Income and bianzhi were the two key attributes influencing the job choices and retention preferences of CDC workers. Heterogeneity in job preferences was also identified. Based on the preference characteristics of different subgroups, policy content should be skewed to differentiate the importance of incentives.
China
;
Humans
;
Male
;
Female
;
Adult
;
Centers for Disease Control and Prevention, U.S.
;
Middle Aged
;
Choice Behavior
;
Career Choice
;
Motivation
3.Effect of HSYA on LCN2-induced iron death of HT22 cells and its mechanism based on SLC7A11/GPX4 signaling pathway
Meng-wei RONG ; Cun-yan DAN ; Tian-qing XIA ; Yi YANG ; Xiu LOU ; Chen-xiang JI ; Bao-guo XIAO ; Cun-gen MA ; Li-juan SONG
Chinese Pharmacological Bulletin 2025;41(11):2097-2105
Aim To explore the effect of hydroxysafflor yellow A(HSYA)on lipocalin 2(LCN2)-induced fer-roptosis in HT22 cells and the related mechanism.Methods Thirty male Sprague-Dawley(SD)rats were used to establish the middle cerebral artery occlu-sion/reperfusion(MCAO/R)model by the suture method.The rats were randomly divided into the Sham group,the MCAO/R group,and the MCAO/R+HSYA group.The infarct area was measured by TTC staining,and the degree of neurological deficit was evaluated by the Z-Longa scoring method.The expressions of LCN2 and 24P3R in brain tissues were detected by Western blot.LCN2 protein was added to HT-22 cells,and the cells were divided into the normal group,the LCN2 group,and the LCN2+HSYA group.The optimal con-centration of LCN2-induced neuronal ferroptosis was screened by LDH assay and Western blot,and the ex-pression levels of ferritin,FPN1,GPX4,SLC7A11,COX2,and 24P3R were detected.LCN2 was knocked down by siRNA transfection,and the expressions of GPX4 and ferritin were detected.The contents of glu-tathione(GSH),malondialdehyde(MDA),GPX4,and Fe2+were determined by colorimetry,and the expres-sion of GPX4 was detected by immunofluorescence.The binding force between HSYA and LCN2 was ana-lyzed by molecular docking technology.Results Ani-mal experiments showed that HSYA could reduce the cerebral infarction area and decrease the neurological function score of MCAO/R rats.Compared with the sham group,the levels of LCN2 and 24P3R increased in the MCAO/R group,while HSYA inhibited their ex-pressions.Cell experiments showed that the optimal concentration of LCN2 to induce ferroptosis in HT22 cells was 2 μmol·L-1.After knocking down LCN2 by siRNA transfection,compared with the LCN2 group,the expression levels of GPX4 and ferritin in the siLCN2 group increased significantly.Compared with the nor-mal group,the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH in the LCN2 group decreased signifi-cantly,while the concentration of Fe2+,and the expres-sions of MDA,COX2,and 24P3R increased.HSYA could increase the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH,reduce the contents of Fe2+and MDA,and inhibit the expressions of COX2 and 24P3R.Molecular docking showed that the binding en-ergy between HSYA and LCN2 was-8.0 kJ·mol-1.Conclusion HSYA can inhibit LCN2-induced ferrop-tosis in HT22 cells through the SLC7A11/GPX4 signa-ling pathway.
4.Analysis of Lung Cancer Screening Compliance Among High-Risk Population in Chongqing from 2013 to 2021
Lu XIAO ; Shenglin ZHAO ; Zhikai YU ; Jia DU ; Yan ZHANG ; Xiu LIU ; Qing GUO ; Hong ZHOU ; Mei HE
China Cancer 2025;34(3):203-208
[Purpose]To analyze the compliance and its influencing factors of lung cancer screening using low-dose computed tomography(LDCT)among high-risk population in urban districts of Chongqing from 2013 to 2021.[Methods]The lung cancer screeing of Cancer Early Diagnosis and Treatment Project was conducted among permanent residents aged 40~69 years old from 14 urban districts of Chongqing selected by cluster sampling method from 2013 to 2021.The questionnaire survey was performed to assess the risk level of lung cancer,and individuals with high risk were advised to have LDCT examination.The compliance rate of LDCT examination among high-risk populations was calculated and compared using Chi-square test among residents with different de-mographic features;the influencing factors of compliance was analyzed with generalized linear mixed models.[Results]A total of 316 066 residents completed the risk assessment questionnaire survey,52 858 people were assessed as high-risk(17.17%).Among the high-risk population,20 398 completed LDCT screening,with an overall compliance rate of 38.59%.The generalized linear mixed model showed that male participants(OR=0.871,95%CI:0.823~0.922)and smokers(light smokers:OR=0.829,95%CI:0.775~0.886;heavy smokers:OR=0.842,95%CI:0.792~0.896)had lower compliance rates;while people with higher education level(OR=1.347,95%CI:1.265~1.435),occupational exposure to harmful substances(OR=1.400,95%CI:1.340~1.463),passive smoking for 20 years or more(OR=1.472,95%CI:1.376~1.576),infrequent physical exercise(OR=1.203,95%CI:1.152~1.256),family history of lung cancer(OR=2.312,95%CI:2.201~2.429),and those having media promotion by community staff(OR=1.365,95%CI:1.223~1.524),and trained community staff(OR=1.343,95%CI:1.227~1.470)had higher compliance rates.Comorbidities were also factors influencing compliance,and there was an increasing trend of compliance rate with the increase of comorbidity numbers(P<0.001).[Conclusion]The compli-ance rate of LDCT examination for lung cancer screening in Chongqing needs to be improved,and more precise health education should be implemented for groups with different characteristics to improve the compliance among high-risk population.
5.Analysis on Screening Results of Breast Cancer Among Women Aged 45~74 in Chongqing from 2012 to 2022
Jia DU ; Zhikai YU ; Shenglin ZHAO ; Yan ZHANG ; Qing GUO ; Xiu LIU ; Hong ZHOU ; Mei HE
China Cancer 2025;34(1):43-51
[Purpose]To analyze the results of breast cancer screening among women aged 45~74 in Chongqing from 2012 to 2022 and compare the risk of breast cancer among women with differ-ent characteristics.[Methods]The Urban Cancer Early Diagnosis and Treatment Program was con-ducted in Chongqing from 2012 to 2022,female residents aged 45~74 years old participated in breast cancer screening.The participants who were assessed as at high risk of breast cancer in the preliminary screening were advised to receive ultrasonography and mammography examination in designated hospitals.The study population was followed up annually to obtain information on their health outcomes.The high risk rate of breast cancer,compliance of further examination,the inci-dence density and breast cancer risk were calculated.[Results]A total of 207 891 women com-pleted the questionnaires survey and risk assessment,and 35 947 were assessed as the individuals with high risk of breast cancer with a high risk rate of 17.29%.Among them 14 713 received the imaging screening with a compliance rate of 40.93%.After a mean follow-up of(5.43±3.01)years,847 cases of breast cancer were diagnosed with a cumulative incidence rate of 407.43/105,an in-cidence density of 75.03/105 person-years(95%CI:70.15/105~80.26/105 person-years).Cox pro-portional hazards regression showed that the risk of breast cancer was higher in obese women than that in normal weight women(HR=1.26,95%CI:1.00~1.59);the risk of breast cancer was signifi-cantly higher in those with family history of breast cancer than that in those without family history(HR=1.69,95%CI:1.36~2.09).Compared with non-high-risk groups of breast cancer,the risk of breast cancer was increased in high-risk individuals who were screened or not screened(HR=1.36,95%CI:1.06~1.73 and HR=1.26,95%CI:1.01~1.56).[Conclusion]The breast cancer screening program combining primary risk assessment with ultrasonography and mammography for the high-risk groups can improve the detection rate,and the compliance rate of imaging screening need to be improved in the future and make accurate screening for people with high risk of breast cancer.
6.Clinical Characteristics and Prognosis of B-cell Acute Lymphoblastic Leukemia Patients with IKZF1 Deletion
Li-Hua WANG ; Yan GUO ; Yuan ZHANG ; Xiu-Feng WANG ; Xian-Kai LIU ; Yan HUANG
Journal of Experimental Hematology 2025;33(4):966-971
Objective:To analyze clinical characteristics and prognosis of B-cell acute lymphoblastic leukemia(B-ALL)patients with IKZF1 deletion.Methods:72 patients with B-ALL admitted to our hospital from April 2020 to January 2023 were selected,IKZF1 deletion were detected,and clinical characteristics and prognosis were analyzed.Results:Among the 72 patients,a total of 32 patients(44.4%)were identified with IKZF1 deletions(IKZF1+).There was no statistically significant difference in basic clinical data between patients with normal IKZF1(IKZF1-)and those with IKZF1+(P>0.05).The proportion of patients with IKZF1+in Ph+group was significantly higher than that in Ph-group(P<0.05).The main types of IKZF1+were exon 1-8 deletion(34.4%)and exon 4-7 deletion(31.2%).The median OS and PFS of IKZF1-patients were significantly longer than those of IKZF1+patients(OS:26.0 months vs 16.0 months,x2=23.094,P<0.05;PFS:26.0 months vs 16.0 months,x2=11.150,P<0.05).Among IKZF1+patients,the median OS of patients who received allogeneic hematopoietic stem cell transplantation(allo-HSCT)was significantly longer than that of patients who did not receive allo-HSCT(no reached vs 15.0 months,x2=5.685,P<0.05).Conclusion:IKZF1 deletion is a risk factor affecting the prognosis of B-ALL patients.
7.Correlation Analysis of Inflammatory Indexes and Bone Marrow Cytological Characteristics with Prognosis in Patients with Hemophagocytic Lymphohistiocytosis
Guo-Xiang CHEN ; Jian-Shu HAO ; Qing-Qing ZHANG ; Hai-Xia AN ; Yan-Qing SUN ; Xiu-Juan HUANG
Journal of Experimental Hematology 2025;33(4):1086-1093
Objective:To investigate the clinical characteristics and prognosis of patients with hemophagocytic lymphohistiocytosis(HLH).Methods:Clinical data of 78 patients with HLH admitted to Gansu Provincial People's Hospital from January 2014 to May 2023 were collected,and the correlation between relevant indicators and patient prognosis was analyzed.Results:Among the 78 HLH patients,there were 48 males and 30 females,with a median age of onset of 48(1-84)years old;26 patients were treated with chemotherapy,44 patients were treated with glucocorticoids,immunoglobulin or cyclosporine,5 patients received symptomatic treatment,1 patient received plasma exchange,and 2 patients refused treatment.By the end of the follow-up,there were 39 survivors,35 deaths,and 4 patients lost to follow-up.There was no significant correlation between sex,ferritin,triglycerides,hemophagocytosis,bone marrow cellularity,Epstein-Barr virus(EBV)infection,SUV value of PET-CT,alanine aminotransferase(ALT),interleukin-6(IL-6),platelet-to-lymphocyte ratio(PLR)and overall survival(OS)of the patients(P>0.05).Patients with age ≥ 60 years,neutrophil-to-lymphocyte ratio(NLR)>0.59,red cell distribution width-to-platelet ratio(RPR)>0.30,lymphocyte-to-monocyte ratio(LMR)≤ 2.74,red blood cell distribution width(RDW)>16.45%,tumor-associated HLH,aspartate aminotransferase(AST)≥ 148 U/L,procalcitonin(PCT)≥ 0.66 ng/ml,neutrophils(NEU)<2 × 109/L,fibrinogen(FIB)<1.85 g/L,lactate dehydrogenase(LDH)≥ 1 740 U/L,hemoglobin(Hb)<85 g/L,platelet(PLT)<57 × 109/L had significantly shorter OS,with statistical significance(P<0.05).Multivariate analysis showed that LMR ≤ 2.74,RDW>16.45%,LDH ≥ 1 740 U/L,and NEU<2 × 109/L were independent risk factors affecting OS in HLH patients(P<0.05).Conclusion:Some blood-based inflammatory markers are significantly associated with OS in patients with HLH.NLR,RPR,LMR,RDW and PCT can be used to assess the prognosis of HLH patients,and RDW and LMR are independent factors affecting OS of HLH patients,which provide greater predictive value for prognosis.Hypercellular bone marrow in HLH patients may indicate a poor prognosis.
8.Analysis of Lung Cancer Screening Compliance Among High-Risk Population in Chongqing from 2013 to 2021
Lu XIAO ; Shenglin ZHAO ; Zhikai YU ; Jia DU ; Yan ZHANG ; Xiu LIU ; Qing GUO ; Hong ZHOU ; Mei HE
China Cancer 2025;34(3):203-208
[Purpose]To analyze the compliance and its influencing factors of lung cancer screening using low-dose computed tomography(LDCT)among high-risk population in urban districts of Chongqing from 2013 to 2021.[Methods]The lung cancer screeing of Cancer Early Diagnosis and Treatment Project was conducted among permanent residents aged 40~69 years old from 14 urban districts of Chongqing selected by cluster sampling method from 2013 to 2021.The questionnaire survey was performed to assess the risk level of lung cancer,and individuals with high risk were advised to have LDCT examination.The compliance rate of LDCT examination among high-risk populations was calculated and compared using Chi-square test among residents with different de-mographic features;the influencing factors of compliance was analyzed with generalized linear mixed models.[Results]A total of 316 066 residents completed the risk assessment questionnaire survey,52 858 people were assessed as high-risk(17.17%).Among the high-risk population,20 398 completed LDCT screening,with an overall compliance rate of 38.59%.The generalized linear mixed model showed that male participants(OR=0.871,95%CI:0.823~0.922)and smokers(light smokers:OR=0.829,95%CI:0.775~0.886;heavy smokers:OR=0.842,95%CI:0.792~0.896)had lower compliance rates;while people with higher education level(OR=1.347,95%CI:1.265~1.435),occupational exposure to harmful substances(OR=1.400,95%CI:1.340~1.463),passive smoking for 20 years or more(OR=1.472,95%CI:1.376~1.576),infrequent physical exercise(OR=1.203,95%CI:1.152~1.256),family history of lung cancer(OR=2.312,95%CI:2.201~2.429),and those having media promotion by community staff(OR=1.365,95%CI:1.223~1.524),and trained community staff(OR=1.343,95%CI:1.227~1.470)had higher compliance rates.Comorbidities were also factors influencing compliance,and there was an increasing trend of compliance rate with the increase of comorbidity numbers(P<0.001).[Conclusion]The compli-ance rate of LDCT examination for lung cancer screening in Chongqing needs to be improved,and more precise health education should be implemented for groups with different characteristics to improve the compliance among high-risk population.
9.Genetic profiling and intervention strategies for phenylketonuria in Gansu, China: an analysis of 1 159 cases.
Chuan ZHANG ; Pei ZHANG ; Bing-Bo ZHOU ; Xing WANG ; Lei ZHENG ; Xiu-Jing LI ; Jin-Xian GUO ; Pi-Liang CHEN ; Ling HUI ; Zhen-Qiang DA ; You-Sheng YAN
Chinese Journal of Contemporary Pediatrics 2025;27(7):808-814
OBJECTIVES:
To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies.
METHODS:
A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene.
RESULTS:
For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295).
CONCLUSIONS
Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans
;
Phenylketonurias/epidemiology*
;
Female
;
Male
;
Retrospective Studies
;
Phenylalanine Hydroxylase/genetics*
;
Mutation
;
Child, Preschool
;
China/epidemiology*
;
Child
;
Infant
10.Analysis on Screening Results of Breast Cancer Among Women Aged 45~74 in Chongqing from 2012 to 2022
Jia DU ; Zhikai YU ; Shenglin ZHAO ; Yan ZHANG ; Qing GUO ; Xiu LIU ; Hong ZHOU ; Mei HE
China Cancer 2025;34(1):43-51
[Purpose]To analyze the results of breast cancer screening among women aged 45~74 in Chongqing from 2012 to 2022 and compare the risk of breast cancer among women with differ-ent characteristics.[Methods]The Urban Cancer Early Diagnosis and Treatment Program was con-ducted in Chongqing from 2012 to 2022,female residents aged 45~74 years old participated in breast cancer screening.The participants who were assessed as at high risk of breast cancer in the preliminary screening were advised to receive ultrasonography and mammography examination in designated hospitals.The study population was followed up annually to obtain information on their health outcomes.The high risk rate of breast cancer,compliance of further examination,the inci-dence density and breast cancer risk were calculated.[Results]A total of 207 891 women com-pleted the questionnaires survey and risk assessment,and 35 947 were assessed as the individuals with high risk of breast cancer with a high risk rate of 17.29%.Among them 14 713 received the imaging screening with a compliance rate of 40.93%.After a mean follow-up of(5.43±3.01)years,847 cases of breast cancer were diagnosed with a cumulative incidence rate of 407.43/105,an in-cidence density of 75.03/105 person-years(95%CI:70.15/105~80.26/105 person-years).Cox pro-portional hazards regression showed that the risk of breast cancer was higher in obese women than that in normal weight women(HR=1.26,95%CI:1.00~1.59);the risk of breast cancer was signifi-cantly higher in those with family history of breast cancer than that in those without family history(HR=1.69,95%CI:1.36~2.09).Compared with non-high-risk groups of breast cancer,the risk of breast cancer was increased in high-risk individuals who were screened or not screened(HR=1.36,95%CI:1.06~1.73 and HR=1.26,95%CI:1.01~1.56).[Conclusion]The breast cancer screening program combining primary risk assessment with ultrasonography and mammography for the high-risk groups can improve the detection rate,and the compliance rate of imaging screening need to be improved in the future and make accurate screening for people with high risk of breast cancer.

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