1.Praeruptorin A inhibits neutrophil inflammation through ferritin and its role in sepsis
Pengchao YU ; Hong ZHENG ; Yifan HU ; Zhouxin YANG ; Zejia YU ; Jinnan XIA ; Haiying HAN ; Dongyang GUO
Chinese Journal of Microbiology and Immunology 2025;45(3):248-255
Objective:To investigate the potential of praeruptorin A (PA) in alleviating inflammatory damage in sepsis through the inhibition of ferritin expression.Methods:C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) to establish the model of sepsis. After 6 and 12 h of PA intervention, serum levels of inflammatory cytokines IL-6 and TNF-α were measured by ELISA. Kidney tissues were collected at 72 h for HE staining to assess inflammatory cell infiltration and tissue damage. Human neutrophils were divided into four groups: control, LPS, ferritin, and LPS+ ferritin groups. After 12 h of intervention, qRT-PCR was used to detect the expression of IL-6 and TNF-α mRNA. In order to observe the effect of PA on the expression of inflammatory cytokines and ferritin, human neutrophils were grouped into control, LPS, and LPS+ PA (2/3/4 μmol/L) groups. After 12 h of intervention, qRT-PCR was performed to measure the expression of IL-1β, IL-6, TNF-α, and ferritin mRNA; ELISA was used to quantify the levels of IL-1β, IL-6, and TNF-α in culture supernatants; Western blot was used to analyze the expression of ferritin. Molecular docking was conducted to verify interactions between PA and ferritin.Results:Significant inflammatory cell recruitment, tissue damage, and elevated serum levels of IL-6 and TNF-α ( P<0.01) were observed in mice with LPS-induced sepsis. PA significantly inhibited cytokine secretion ( P<0.01) and alleviated tissue injury in sepsis mice. In human neutrophil models, ferritin upregulated the expression of IL-6 and TNF-α mRNA ( P<0.01); LPS stimulation alone increased the expression of IL-1β, IL-6, TNF-α, and ferritin at both mRNA and protein levels ( P<0.01), while co-stimulation with PA (3/4 μmol/L) significantly reversed the aforementioned results ( P<0.01). Molecular docking confirmed there were interaction sites between PA and ferritin. Conclusion:PA inhibits the release of inflammatory cytokines and alleviates tissue damage in sepsis, and the potential mechanism may involve modulating ferritin expression to suppress inflammatory responses.
2.Tetanus antibody levels in healthy people in Henan Province from 2022 to 2023
Qian LIU ; Jiangnan KONG ; Daxing FENG ; Yonghao GUO ; Minghua SENG ; Yuting TANG ; Yanyang ZHANG ; Dongyang ZHAO ; Linqi DIAO
Chinese Journal of Preventive Medicine 2025;59(8):1239-1245
Objective:To investigate tetanus antibody levels and distribution characteristics in a healthy population of Henan Province.Methods:A cross-sectional survey was conducted in Henan Province from 2022 to 2023 to investigate the permanent population. Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-tetanus toxoid IgG antibody (anti-TT), and the positive rate (≥0.01 IU/ml), protection rate (≥0.1 IU/ml) and concentration differences of tetanus antibodies in different populations were analyzed.Results:The age M ( Q1, Q3) of 5 494 participants was 14 (4, 40) years old, with a minimum age of 8 months and a maximum age of 81 years old. The male-to-female ratio was 1.00∶1.18. The total positive rate, protective rate and mean concentration (MC) [ M ( Q1, Q3)] of Anti-TT were 76.48%, 41.72% and 0.067 (0.010, 0.154) IU/ml, respectively. The positive rates of Anti-TT in individuals aged <3, 3-5, 6-9, and 10-14 were 95.32%, 96.05%, 97.81%, and 93.17%, respectively, but gradually decreased with age ( χ2trend=1 283.02, P<0.001). The antibody protection rate [82.13% (579/705)] and MC [ M ( Q1, Q3) of 0.160 (0.122, 0.259) IU/ml] in the population under 3 years old were relatively high, and both showed a decreasing trend with age (protection rate: χ2trend=1 889.49, P<0.001; MC: t=-54.22, P<0.001). There were significant differences in antibody levels among populations of different ages, regions, occupations, and immunization histories (all P<0.001). Within 13 years after the last dose of TTCV vaccination, the positive rate of Anti-TT was all greater than 90%, but the protection rate and MC continued to decrease with the prolongation of vaccination time (protection rate: χ2trend=160.58, P<0.001; MC: t=-14.93, P<0.001). After the last dose of vaccination, the protection rate and MC [ M ( Q1, Q3)] decreased to 30.43% and 0.055 (0.036, 0.115) IU/ml, respectively, for 10-13 years. The protection rates of Anti-TT for farmers, workers, people aged 60 and above, and women of childbearing age (20-45 years old) were 7.77%, 22.96%, 8.39%, and 12.72%, respectively. Conclusion:The level of tetanus antibodies in infants and young children in Henan Province is relatively high from 2022 to 2023, but it decreases with age and prolonged post-immunization time. There are significant differences in antibody levels among individuals of different ages, regions, occupations, and immunization histories. Occupational high-risk groups such as farmers and workers, elderly people, and women of childbearing age lack sufficient immunization protection.
3.Epidemiological and molecular traceability analysis of the first cluster outbreak of D8 genotype measles in Henan Province
Xiaoxiao ZHANG ; Binghui DU ; Daxing FENG ; Wenhui WANG ; Jing LI ; Lili LIU ; Hui ZI ; Qihua WAN ; Songtao ZHAO ; Xiaoli WANG ; Xiaobo WU ; Yonghao GUO ; Yanyang ZHANG ; Dongyang ZHAO
Chinese Journal of Preventive Medicine 2025;59(8):1294-1298
In February 2025, a local cluster outbreak caused by the D8 genotype Measles virus (MV) was first discovered in Henan Province. Epidemiological investigations and laboratory testing were conducted, including the collection of serum and throat swabs for MV IgM antibody and nucleic acid detection, virus isolation and genetic homology analysis. Measures such as close contact tracing, vaccination rate assessment and supplementary immunization activities were implemented, successfully preventing broader community transmission. A total of three cases were reported during the outbreak, including one imported-related adolescent and two secondary local adult cases. All cases presented with typical symptoms such as fever and rash. Both adult cases were complicated by pneumonia, with one case developing into severe pneumonia. MV genotyping showed that the two secondary cases were both the D8 genotype, with the viral sequences being completely homologous to the Kazakhstan strain. Among the close contacts, 98.2% were adults, and 142 individuals received emergency vaccination.
4.Tetanus antibody levels in healthy people in Henan Province from 2022 to 2023
Qian LIU ; Jiangnan KONG ; Daxing FENG ; Yonghao GUO ; Minghua SENG ; Yuting TANG ; Yanyang ZHANG ; Dongyang ZHAO ; Linqi DIAO
Chinese Journal of Preventive Medicine 2025;59(8):1239-1245
Objective:To investigate tetanus antibody levels and distribution characteristics in a healthy population of Henan Province.Methods:A cross-sectional survey was conducted in Henan Province from 2022 to 2023 to investigate the permanent population. Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-tetanus toxoid IgG antibody (anti-TT), and the positive rate (≥0.01 IU/ml), protection rate (≥0.1 IU/ml) and concentration differences of tetanus antibodies in different populations were analyzed.Results:The age M ( Q1, Q3) of 5 494 participants was 14 (4, 40) years old, with a minimum age of 8 months and a maximum age of 81 years old. The male-to-female ratio was 1.00∶1.18. The total positive rate, protective rate and mean concentration (MC) [ M ( Q1, Q3)] of Anti-TT were 76.48%, 41.72% and 0.067 (0.010, 0.154) IU/ml, respectively. The positive rates of Anti-TT in individuals aged <3, 3-5, 6-9, and 10-14 were 95.32%, 96.05%, 97.81%, and 93.17%, respectively, but gradually decreased with age ( χ2trend=1 283.02, P<0.001). The antibody protection rate [82.13% (579/705)] and MC [ M ( Q1, Q3) of 0.160 (0.122, 0.259) IU/ml] in the population under 3 years old were relatively high, and both showed a decreasing trend with age (protection rate: χ2trend=1 889.49, P<0.001; MC: t=-54.22, P<0.001). There were significant differences in antibody levels among populations of different ages, regions, occupations, and immunization histories (all P<0.001). Within 13 years after the last dose of TTCV vaccination, the positive rate of Anti-TT was all greater than 90%, but the protection rate and MC continued to decrease with the prolongation of vaccination time (protection rate: χ2trend=160.58, P<0.001; MC: t=-14.93, P<0.001). After the last dose of vaccination, the protection rate and MC [ M ( Q1, Q3)] decreased to 30.43% and 0.055 (0.036, 0.115) IU/ml, respectively, for 10-13 years. The protection rates of Anti-TT for farmers, workers, people aged 60 and above, and women of childbearing age (20-45 years old) were 7.77%, 22.96%, 8.39%, and 12.72%, respectively. Conclusion:The level of tetanus antibodies in infants and young children in Henan Province is relatively high from 2022 to 2023, but it decreases with age and prolonged post-immunization time. There are significant differences in antibody levels among individuals of different ages, regions, occupations, and immunization histories. Occupational high-risk groups such as farmers and workers, elderly people, and women of childbearing age lack sufficient immunization protection.
5.Epidemiological and molecular traceability analysis of the first cluster outbreak of D8 genotype measles in Henan Province
Xiaoxiao ZHANG ; Binghui DU ; Daxing FENG ; Wenhui WANG ; Jing LI ; Lili LIU ; Hui ZI ; Qihua WAN ; Songtao ZHAO ; Xiaoli WANG ; Xiaobo WU ; Yonghao GUO ; Yanyang ZHANG ; Dongyang ZHAO
Chinese Journal of Preventive Medicine 2025;59(8):1294-1298
In February 2025, a local cluster outbreak caused by the D8 genotype Measles virus (MV) was first discovered in Henan Province. Epidemiological investigations and laboratory testing were conducted, including the collection of serum and throat swabs for MV IgM antibody and nucleic acid detection, virus isolation and genetic homology analysis. Measures such as close contact tracing, vaccination rate assessment and supplementary immunization activities were implemented, successfully preventing broader community transmission. A total of three cases were reported during the outbreak, including one imported-related adolescent and two secondary local adult cases. All cases presented with typical symptoms such as fever and rash. Both adult cases were complicated by pneumonia, with one case developing into severe pneumonia. MV genotyping showed that the two secondary cases were both the D8 genotype, with the viral sequences being completely homologous to the Kazakhstan strain. Among the close contacts, 98.2% were adults, and 142 individuals received emergency vaccination.
6.Praeruptorin A inhibits neutrophil inflammation through ferritin and its role in sepsis
Pengchao YU ; Hong ZHENG ; Yifan HU ; Zhouxin YANG ; Zejia YU ; Jinnan XIA ; Haiying HAN ; Dongyang GUO
Chinese Journal of Microbiology and Immunology 2025;45(3):248-255
Objective:To investigate the potential of praeruptorin A (PA) in alleviating inflammatory damage in sepsis through the inhibition of ferritin expression.Methods:C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) to establish the model of sepsis. After 6 and 12 h of PA intervention, serum levels of inflammatory cytokines IL-6 and TNF-α were measured by ELISA. Kidney tissues were collected at 72 h for HE staining to assess inflammatory cell infiltration and tissue damage. Human neutrophils were divided into four groups: control, LPS, ferritin, and LPS+ ferritin groups. After 12 h of intervention, qRT-PCR was used to detect the expression of IL-6 and TNF-α mRNA. In order to observe the effect of PA on the expression of inflammatory cytokines and ferritin, human neutrophils were grouped into control, LPS, and LPS+ PA (2/3/4 μmol/L) groups. After 12 h of intervention, qRT-PCR was performed to measure the expression of IL-1β, IL-6, TNF-α, and ferritin mRNA; ELISA was used to quantify the levels of IL-1β, IL-6, and TNF-α in culture supernatants; Western blot was used to analyze the expression of ferritin. Molecular docking was conducted to verify interactions between PA and ferritin.Results:Significant inflammatory cell recruitment, tissue damage, and elevated serum levels of IL-6 and TNF-α ( P<0.01) were observed in mice with LPS-induced sepsis. PA significantly inhibited cytokine secretion ( P<0.01) and alleviated tissue injury in sepsis mice. In human neutrophil models, ferritin upregulated the expression of IL-6 and TNF-α mRNA ( P<0.01); LPS stimulation alone increased the expression of IL-1β, IL-6, TNF-α, and ferritin at both mRNA and protein levels ( P<0.01), while co-stimulation with PA (3/4 μmol/L) significantly reversed the aforementioned results ( P<0.01). Molecular docking confirmed there were interaction sites between PA and ferritin. Conclusion:PA inhibits the release of inflammatory cytokines and alleviates tissue damage in sepsis, and the potential mechanism may involve modulating ferritin expression to suppress inflammatory responses.
7.Seroepidemiological analysis of hepatitis B virus infection among adolescents aged 0-14 years in Henan Province and preliminary evaluation of the effectiveness of childhood hepatitis B vaccine immunization program
Yonghao GUO ; Yanping CHEN ; Qiaohua DOU ; Qian LIU ; Jianhui YANG ; Minghua SENG ; Wanyu LYU ; Changshuang WANG ; Mingxia LU ; Jin XU ; Yanyang ZHANG ; Dongyang ZHAO
Chinese Journal of Preventive Medicine 2024;58(2):202-207
Objective:To analyze the seroepidemiological characteristics of hepatitis B virus (HBV) infection among adolescents aged 0-14 years in Henan Province and to evaluate the effectiveness of the childhood hepatitis B vaccine (HepB) immunization program.Methods:From September 2021 to March 2022, a total of 4 883 adolescents aged 0-14 years were selected from 25 villages or communities of 18 provincial-level cities in Henan Province by using the multi-stage random cluster sampling method. Demographic data were collected through questionnaires. The 3 ml of blood samples were collected from individuals aged 0-4 years and 5 ml of blood samples were collected from individuals aged 5-14 years to test HBsAg, HBcAb and HBsAb. Data on vaccination were collected through Henan Provincial Immunization Information System and hepatitis B cases in Henan Province were collected through China Infectious Disease Reporting System. The effectiveness of the childhood HepB immunization program was analyzed.Results:The average age of 4 883 subjects was (7.32±2.81) years old. The positive rates of HBsAg and HBcAb were 0.1% (7/4 883) and 1.0% (50/4 883), and the population standardized rates were 0.3% and 1.7%. In 2002, the positive rate of HBsAg among adolescents aged 0-14 years in Henan Province was 3.39%. Compared with that in 2002, the number of chronic HBV infections among adolescents in Henan Province in 2022 decreased by about 0.7 million. In 2002, the vaccination rate of newborns who completed all three doses of vaccine was 6.26%. In 2003, the vaccination rate of the hepatitis B vaccine rose rapidly, reaching 90% in 2013 for the first time. After 2014, the vaccination rate in Henan Province continued to remain above 95%. The proportion of cases among children aged 1-4 years in clinical reports decreased from 0.43% (1 108/256 566) in 2006 to 0.01% (78/80 655) in 2021. The proportion of cases among adolescents aged 5-19 years decreased from 18.21% (46 710/256 566) in 2006 to 1.1% (827/80 655) in 2021.Conclusions:From 2002 to 2022, the positive rate of HBsAg among adolescents aged 0-14 years has decreased significantly in Henan Province. The effectiveness of the HepB immunization program for children is good.
8.Improvement of insulin sensitivity in T2DM patients by glucagon-like peptide fusion protein
Huan LIU ; Yang LIU ; Dan LUO ; Lixin GUO ; Dongyang LIU
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(8):879-886
AIM:In order to quantitatively exam-ine the improvement of insulin sensitivity(IS)in pa-tients with type 2 diabetes mellitus(T2DM)when exendin-4-lgG4-Fc(E4F4)was given for 12 weeks,the present study was conducted to establish E4F4 population oral glucose minimal models based on the meal tolerance test(MTT)data of E4F4 pre-and post-dosing,and to analyze whether low-dose(2.7 mg)administration for 12 weeks significantly improved insulin sensitivity in patients with T2DM.METHODS:Blood glucose and insulin concentra-tions were collected among 16 subjects in the study who completed MTT before or after dosing.Nonlinear mixed-effects model construction for the population oral glucose minimal models was per-formed using NONMEN 7.2 software using pre-and post-dosing data,respectively.The insulin sensitivi-ty parameters obtained from the models before and after the administration of the drug were sta-tistically analyzed using GraphPad Prism 8.0.RE-SULTS:Nonparametric test of IS before and after dosing showed statistical difference(P=0.02),and insulin sensitivity after dosing was significantly higher than the baseline value before dosing.CON-CLUSION:12 weeks of low-dose E4F4 treatment in patients with type 2 diabetes mellitus resulted in an improvement in insulin sensitivity.This study provides a pharmacodynamic basis for the efficacy of this novel biologic.
9.Seroepidemiological analysis of hepatitis B virus infection among adolescents aged 0-14 years in Henan Province and preliminary evaluation of the effectiveness of childhood hepatitis B vaccine immunization program
Yonghao GUO ; Yanping CHEN ; Qiaohua DOU ; Qian LIU ; Jianhui YANG ; Minghua SENG ; Wanyu LYU ; Changshuang WANG ; Mingxia LU ; Jin XU ; Yanyang ZHANG ; Dongyang ZHAO
Chinese Journal of Preventive Medicine 2024;58(2):202-207
Objective:To analyze the seroepidemiological characteristics of hepatitis B virus (HBV) infection among adolescents aged 0-14 years in Henan Province and to evaluate the effectiveness of the childhood hepatitis B vaccine (HepB) immunization program.Methods:From September 2021 to March 2022, a total of 4 883 adolescents aged 0-14 years were selected from 25 villages or communities of 18 provincial-level cities in Henan Province by using the multi-stage random cluster sampling method. Demographic data were collected through questionnaires. The 3 ml of blood samples were collected from individuals aged 0-4 years and 5 ml of blood samples were collected from individuals aged 5-14 years to test HBsAg, HBcAb and HBsAb. Data on vaccination were collected through Henan Provincial Immunization Information System and hepatitis B cases in Henan Province were collected through China Infectious Disease Reporting System. The effectiveness of the childhood HepB immunization program was analyzed.Results:The average age of 4 883 subjects was (7.32±2.81) years old. The positive rates of HBsAg and HBcAb were 0.1% (7/4 883) and 1.0% (50/4 883), and the population standardized rates were 0.3% and 1.7%. In 2002, the positive rate of HBsAg among adolescents aged 0-14 years in Henan Province was 3.39%. Compared with that in 2002, the number of chronic HBV infections among adolescents in Henan Province in 2022 decreased by about 0.7 million. In 2002, the vaccination rate of newborns who completed all three doses of vaccine was 6.26%. In 2003, the vaccination rate of the hepatitis B vaccine rose rapidly, reaching 90% in 2013 for the first time. After 2014, the vaccination rate in Henan Province continued to remain above 95%. The proportion of cases among children aged 1-4 years in clinical reports decreased from 0.43% (1 108/256 566) in 2006 to 0.01% (78/80 655) in 2021. The proportion of cases among adolescents aged 5-19 years decreased from 18.21% (46 710/256 566) in 2006 to 1.1% (827/80 655) in 2021.Conclusions:From 2002 to 2022, the positive rate of HBsAg among adolescents aged 0-14 years has decreased significantly in Henan Province. The effectiveness of the HepB immunization program for children is good.
10.Galangin inhibits the pyroptosis of macrophages mediated by NOD-like receptor proteins 3
Lingzhi SHEN ; Li LI ; Zhouxin YANG ; Dongyang GUO ; Changqin CHEN ; Jing YAN
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(1):28-33
Objective To investigate the effect of Galangin on pyroptosis of bone marrow derived macrophages(BMDMs).Methods BMDMs were cultured in vitro and divided into blank control group,model group and Galangin group with different concentrations.Lipopolysaccharide(LPS)and adenosine triphosphate(ATP)were used to construct the pyroptosis model.The effect of different concentrations of Galangin on the proliferation of BMDMs was detected by cell counting Kit-8(CCK-8).The level of cysteinyl aspartate specific proteinase-1 p10 subunit(caspase-1 p10),interleukin-1β(IL-1β)in supernatant and intracellular nucleotide NOD-like receptor protein 3(NLRP3)were detected by Western blotting.IL-1β in supernatant was detected by enzyme-linked immunosorbent assay(ELISA).The cell death was observed by propidium iodide(PI)staining.High-throughput sequencing was used to compare the gene expression in the model group and Galangin groups at 20 μmol/L.Results There was no statistically significant difference between the 5,10,20,40,60,80 μmol/L Galangin groups on the proliferation level of BMDMs(all P>0.05),indicating that no significant effect of Galangin at 5,10,20,40,60,80 μmol/L was observed on the proliferation of BMDMs.So we selected Galangin at 5,10,20 μmol/L and treatment for 1,2 and 4 hours as the effects of different concentrations and time on the pyroptosis of BMDMs.Compared with blank control group,the expression of caspase-1 p10 and mature IL-1β protein and IL-1β in supernatant in model group were significantly increased(all P<0.05).Compared with model group,the expression of caspase-1 p10 and mature IL-1β protein and IL-1β in supernatant of Galangin at 5,10 and 20 μmol/L were significantly decreased[IL-1β protein expression(gray value):0.155±0.006,0.113±0.006,0.111±0.007 vs.1.000±0.000,caspase-1 p10 protein expression(gray value):0.207±0.044,0.160±0.008,0.082±0.008 vs.1.000±0.000,IL-1β(μg/L):99.80±10.36,85.21±8.78,26.53±4.56 vs.494.10±35.47,all P<0.05].There was no significant difference between the different concentration groups(all P>0.05),but with the extension of treatment time of Galangin,the inhibitory effect was enhanced.The inhibitory effect of Galangin at 20 μmol/L for 4 hours was the most obvious[IL-1β protein expression(gray value):0.186±0.004 vs.1.000±0.000,caspase-1 p10 protein expression(gray value):0.247±0.009 vs.1.000±0.000,IL-1β(μg/L):173.80±10.56 vs.653.80±76.02,all P<0.05].Treatment with 20 μmol/L Galangin for 4 hours could reduce the number of pyroptotic cell deaths(number of view:23.00±3.61 vs.67.67±15.63,P<0.05)and inhibited the expression of NLRP3 protein(gray value:0.178±0.025 vs.0.406±0.066,P<0.05).High-throughput sequencing showed that,compared with the model group,Galangin down-regulated the genes of Nlrp3,Nod2,IL-1β and up-regulated genes of Skp2(also known as Fbxl1),Fbxl20,Fbxl4,Fbxo32 and Fbxw7.Conclusion Galangin inhibited pyroptosis mediated by NLRP3 inflammasome in macrophages.

Result Analysis
Print
Save
E-mail