1.Construction of etiological diagnosis model for pathogen-negative pulmonary tuberculosis using tuberculosis scores of GBP5, DUSP3, and TBP genes combined with inflammatory factors
Miaomiao ZHAO ; Yanyang ZHOU ; Qiuxiang HU ; Hui CHEN ; Tingting CHEN ; Yingqi CHEN ; Ping XU
Chinese Journal of Preventive Medicine 2025;59(11):1965-1971
To evaluate the diagnostic performance of a three-gene (GBP5, DUSP3, and TBP) tuberculosis (TB) score in bacteriologically-negative pulmonary tuberculosis, and to develop and validate a discriminative diagnostic model by integrating inflammatory cytokines (IL-2, IL-5, IL-17, and IFN-γ). A prospective cohort study was conducted, a total of 238 patients admitted to the Affiliated Infectious Disease Hospital of Soochow University from May 2023 to May 2024 were enrolled, including 119 pathogen-negative pulmonary tuberculosis patients and 119 patients with other pulmonary diseases (OPD). The GeneXpert MTB-HR kit was used to detect the three-gene TB scores from residual blood routine samples. The diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis. Concurrent data on 12 inflammatory cytokines were collected from patients. Potential biomarkers were screened using univariate analysis and multivariate logistic regression, and selected features were incorporated into the construction of four machine learning models: logistic regression, support vector machine (SVM), K-nearest neighbors (KNN), and adaptive boosting (AdaBoost). The samples were randomly split into a training set (85%) and a test set (15%). The models were trained on the training set, and their diagnostic performance was validated using the test set. The predictive ability of each model was evaluated based on ROC curve parameters. The results showed that the three-gene TB score alone yielded an AUC of 0.539 (sensitivity: 50.94%, specificity: 60.50%) in distinguishing pathogen-negative pulmonary tuberculosis from OPD. Four non-col-linear inflammatory factors (IL-2, IL-5, IL-17, and IFN-γ) were selected and combined with the three-gene TB score to construct machine learning models. The AdaBoost model demonstrated the best performance, achieving an AUC of 0.893 (sensitivity: 85.4%, specificity: 73.0%) in the training set and an AUC of 0.873 (sensitivity: 88.2%, specificity: 72.2%) in the test set. In conclusion,the AdaBoost diagnostic model integrating the three-gene TB score with inflammatory factors (IL-2, IL-5, IL-17, and IFN-γ) exhibits superior discriminating performance for pathogen-negative pulmonary tuberculosis compared to OPD, significantly outperforming the three-gene TB score alone.
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.Clinical value of guanylate binding protein 5 gene in diagnosis of Mycobacterium tuberculosis infection
Miaomiao ZHAO ; Yanyang ZHOU ; Hui CHEN ; Tingting CHEN ; Ping XU
Chinese Journal of Nosocomiology 2025;35(20):3100-3104
OBJECTIVE To explore the diagnostic value of the guanylate binding protein 5(GBP5)gene in pa-tients infected with Mycobacterium tuberculosis(MTB).METHODS Patients who visited the Fifth People's Hos-pital of Suzhou from Jan.2024 to May 2024,as well as individuals undergoing health examinations during the same period,were selected as the study subjects.Based on the diagnostic criteria,the subjects were divided into active tuberculosis(ATB)group(230 cases),pneumonia group(207 cases),latent tuberculosis infection(LTBI)group(48 cases)and healthy control(HC)group(122 cases).Real-time quantitative reverse transcription poly-merase chain reaction was used to detect the expression level of the GBP 5 gene in the whole blood of the subjects,and receiver operating characteristic(ROC)curves were employed to analyze its diagnostic performance.RESULTS There were statistically significant differences in GBP5 gene expression among the four groups(P<0.001).The area under the ROC curve(AUC)for GBP5 in distinguishing the ATB group from the HC group,LTBI group and pneumonia group was 0.902,0.813 and 0.745,respectively.In the ATB group,the positive de-tection rate of the GBP5 method was 67.39%,higher than that of Gene Xpert MTB/RIF(62.20%),tuberculosis culture(60.00%)and smear acid-fast staining(35.20%)(P<0.05).When distinguishing between ATB and LTBI patients,the positive prediction value of GBP5 was 95.09%,higher than that of IGRA testing(79.92%)(P<0.05).The expression level of GBP5 was negatively correlated with the MTB bacterial load(P<0.001).CONCLUSIONS The detection of the GBP5 gene has important clinical significance in the auxiliary diagno-sis of tuberculosis and can serve as an effective supplement to existing diagnostic methods for tuberculosis.
5.Clinical Features of PD-1/PD-L1 Inhibitors-Related Thyroid Dysfunction in Lung Cancer Patients and Their Predictive Value for Therapeutic Efficacy
Siyi LIN ; Yanyang LIU ; Feng ZHAO ; Qiuxiao JIANG ; Shuyu YANG ; He ZHANG ; Bin FENG ; Wei GAN
Journal of Sichuan University (Medical Sciences) 2025;56(2):514-520
Objective To investigate the clinical features of thyroid dysfunction in lung cancer patients treated with programmed cell death receptor-1(PD-1)or programmed cell death receptor-ligand 1(PD-L1)and their value for predicting therapeutic efficacy.Methods Lung cancer patients treated with PD-1/PD-L1 inhibitors at West China Hospital,Sichuan University between March 2018 and September 2022 were retrospectively enrolled.Data concerning the medical records,therapeutic efficacy,and thyroid function indicators of the patients were retrieved from the hospital electronic medical record information system.The data were then analyzed to identify risk factors and predictive factors for immune-related adverse events(irAEs)of the thyroid.The predictive value of thyroid irAEs for treatment efficacy and prognosis was assessed.Objective response rate(ORR)was defined as the indicator for therapeutic efficacy and progression-free survival(PFS)was defined as the prognostic indicator.Results A total of 368 lung cancer patients were enrolled.Among them,31.5%(116/368)developed thyroid irAEs.According to the results of logistic regression analysis,baseline thyroid stimulating hormone(TSH)concentration and baseline positive results for thyroglobulin antibody(TGAb)and thyroid peroxidase antibody(TPOAb)were risk factors for thyroid dysfunction caused by PD-1/PD-L1 inhibitors.Among the three measures,baseline TPOAb concentration demonstrated good predictive value for thyroid irAEs,with an area under the receiver-operating characteristic(ROC)curve(AUC)of 0.745.Patients with thyroid irAEs had a longer median PFS(16.0 months vs.9.7 months,P<0.001)and a higher ORR(55.2%vs.34.9%,P<0.001)compared to those without thyroid irAEs.Patients with thyroid irAEs had a better ORR than those without thyroid irAEs did.It was more likely for patients with thyroid irAEs to achieve an objective response compared to those without thyroid irAEs(odds ratio[OR]=2.29;95%CI,1.46-3.60).Conclusion In lung cancer patients treated with the PD-1/PD-L1 inhibitors,the TPOAb antibody demonstrates good predictive value for thyroid irAEs.Patients who develop thyroid irAEs have better treatment outcomes and prognosis.
6.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.
7.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.
8.Clinical value of guanylate binding protein 5 gene in diagnosis of Mycobacterium tuberculosis infection
Miaomiao ZHAO ; Yanyang ZHOU ; Hui CHEN ; Tingting CHEN ; Ping XU
Chinese Journal of Nosocomiology 2025;35(20):3100-3104
OBJECTIVE To explore the diagnostic value of the guanylate binding protein 5(GBP5)gene in pa-tients infected with Mycobacterium tuberculosis(MTB).METHODS Patients who visited the Fifth People's Hos-pital of Suzhou from Jan.2024 to May 2024,as well as individuals undergoing health examinations during the same period,were selected as the study subjects.Based on the diagnostic criteria,the subjects were divided into active tuberculosis(ATB)group(230 cases),pneumonia group(207 cases),latent tuberculosis infection(LTBI)group(48 cases)and healthy control(HC)group(122 cases).Real-time quantitative reverse transcription poly-merase chain reaction was used to detect the expression level of the GBP 5 gene in the whole blood of the subjects,and receiver operating characteristic(ROC)curves were employed to analyze its diagnostic performance.RESULTS There were statistically significant differences in GBP5 gene expression among the four groups(P<0.001).The area under the ROC curve(AUC)for GBP5 in distinguishing the ATB group from the HC group,LTBI group and pneumonia group was 0.902,0.813 and 0.745,respectively.In the ATB group,the positive de-tection rate of the GBP5 method was 67.39%,higher than that of Gene Xpert MTB/RIF(62.20%),tuberculosis culture(60.00%)and smear acid-fast staining(35.20%)(P<0.05).When distinguishing between ATB and LTBI patients,the positive prediction value of GBP5 was 95.09%,higher than that of IGRA testing(79.92%)(P<0.05).The expression level of GBP5 was negatively correlated with the MTB bacterial load(P<0.001).CONCLUSIONS The detection of the GBP5 gene has important clinical significance in the auxiliary diagno-sis of tuberculosis and can serve as an effective supplement to existing diagnostic methods for tuberculosis.
9.Construction of etiological diagnosis model for pathogen-negative pulmonary tuberculosis using tuberculosis scores of GBP5, DUSP3, and TBP genes combined with inflammatory factors
Miaomiao ZHAO ; Yanyang ZHOU ; Qiuxiang HU ; Hui CHEN ; Tingting CHEN ; Yingqi CHEN ; Ping XU
Chinese Journal of Preventive Medicine 2025;59(11):1965-1971
To evaluate the diagnostic performance of a three-gene (GBP5, DUSP3, and TBP) tuberculosis (TB) score in bacteriologically-negative pulmonary tuberculosis, and to develop and validate a discriminative diagnostic model by integrating inflammatory cytokines (IL-2, IL-5, IL-17, and IFN-γ). A prospective cohort study was conducted, a total of 238 patients admitted to the Affiliated Infectious Disease Hospital of Soochow University from May 2023 to May 2024 were enrolled, including 119 pathogen-negative pulmonary tuberculosis patients and 119 patients with other pulmonary diseases (OPD). The GeneXpert MTB-HR kit was used to detect the three-gene TB scores from residual blood routine samples. The diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis. Concurrent data on 12 inflammatory cytokines were collected from patients. Potential biomarkers were screened using univariate analysis and multivariate logistic regression, and selected features were incorporated into the construction of four machine learning models: logistic regression, support vector machine (SVM), K-nearest neighbors (KNN), and adaptive boosting (AdaBoost). The samples were randomly split into a training set (85%) and a test set (15%). The models were trained on the training set, and their diagnostic performance was validated using the test set. The predictive ability of each model was evaluated based on ROC curve parameters. The results showed that the three-gene TB score alone yielded an AUC of 0.539 (sensitivity: 50.94%, specificity: 60.50%) in distinguishing pathogen-negative pulmonary tuberculosis from OPD. Four non-col-linear inflammatory factors (IL-2, IL-5, IL-17, and IFN-γ) were selected and combined with the three-gene TB score to construct machine learning models. The AdaBoost model demonstrated the best performance, achieving an AUC of 0.893 (sensitivity: 85.4%, specificity: 73.0%) in the training set and an AUC of 0.873 (sensitivity: 88.2%, specificity: 72.2%) in the test set. In conclusion,the AdaBoost diagnostic model integrating the three-gene TB score with inflammatory factors (IL-2, IL-5, IL-17, and IFN-γ) exhibits superior discriminating performance for pathogen-negative pulmonary tuberculosis compared to OPD, significantly outperforming the three-gene TB score alone.
10.Paeoniflorin ameliorates chronic colitis via the DR3 signaling pathway in group 3 innate lymphoid cells
Huang SHAOWEI ; Xie XUEQIAN ; Xu BO ; Pan ZENGFENG ; Liang JUNJIE ; Zhang MEILING ; Pan SIMIN ; Wang XIAOJING ; Zhao MENG ; Wang QING ; Chen JINYAN ; Li YANYANG ; Zhou LIAN ; Luo XIA
Journal of Pharmaceutical Analysis 2024;14(6):889-901
Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)pre-sents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2%dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2% DSS-induced Rag1-/-mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage indepen-dently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned me-dium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

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