1.Investigation of tumor-suppressive mechanism of Guiqi Yiyuan Extract combined with cisplatin in Lewis lung cancer mice via TXNIP/NLRP3/Caspase-1/GSDMD pathway
Qiong-qiong GUO ; Wen-jie LI ; Jin-tian LI ; Jian-qing LIANG ; Ping TIAN ; Rong HU ; Xu-chao DONG ; Mei-hao XUE ; Long-xin XU
Chinese Traditional Patent Medicine 2025;47(9):2894-2901
AIM To investigate the tumor-suppressive mechanism of Guiqi Yiyuan Extract combined with cisplatin in Lewis lung cancer mice.METHODS Ten intact C57BL/6J mice were assigned to the blank group.Sixty additional mice were developed into Lewis lung cancer models bearing transplanted tumor and subsequently allocated into the model group,the cisplatin group(5 mg/kg),the high-dose Guiqi Yiyuan Extract group(6.6 g/kg),and the low-dose,medium-dose and high-dose Guiqi Yiyuan Extract combined with cisplatin group(1.6,3.3,6.6 g/kg+5 mg/kg),with 10 mice in each group.Mice in the blank and model groups received saline via daily gavage,while treatment groups were administered Guiqi Yiyuan Extract orally(once daily),and cisplatin injection intraperitoneally(once every other day).After 14 days of drug administration,mice were euthanized for endpoint analysis.The following assessments were conducted:general health status and body weight changes monitored throughout the study period;tumor excision and weighing for inhibition rate calculation;histopathological examination of tumors via hematoxylin-eosin(HE)staining;serum quantification of IL-1 β,IL-18 and HMGB1 by ELISA;ultrastructural analysis of tumor cell death using transmission electron microscopy(TEM);spatial localization of TXNIP and GSDMD-N in tumor sections via immunofluorescence(IF);and Western blot detection of TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD,GSDMD-N protein expressions in tumor tissues.RESULTS Compared to the model group,the cisplatin group and all combination therapy groups exhibited significant reduction in tumor weight(P<0.05)and increased tumor suppression rate;enhanced tumor tissue necrosis with characteristic pyroptotic morphology;elevated serum levels of IL-1β,IL-18 and HMGB1(P<0.05);and upregulated expressions of pyroptosis-associated proteins TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD and GSDMD-N(P<0.05).The high dose combination group demonstrated optimal therapeutic efficacy(P<0.05).CONCLUSION Guiqi Yiyuan Extract enhances cisplatin sensitivity,demonstrating synergistic anti-tumor effects in Lewis lung carcinoma-bearing mice.This combinatorial therapeutic effect likely involves modulation of the TXNIP/NLRP3/Caspase-1/GSDMD pathway.
2.Environmental Temperature and the Risk of Hand, Foot, and Mouth Disease Transmission in the Yangtze River Region of China.
Yan Qing YANG ; Min CHEN ; Jin LI ; Kai Qi LIU ; Xue Yan GUO ; Xin XU ; Qian LIANG ; Xing Lu WU ; Su Wen LEI ; Jing LI
Biomedical and Environmental Sciences 2025;38(3):290-302
OBJECTIVE:
To assess health equity in the Yangtze River region to improve understanding of the correlation between hand, foot, and mouth disease (HFMD) and socioeconomic factors.
METHODS:
From 2014-2016, data on HFMD incidence, population statistics, economic indicators, and meteorology from 26 cities along the Yangtze River were analyzed. A multi-city random-effects meta-analysis was performed to study the relationship between temperature and HFMD transmission, and health equity was assessed with respect to socio-economic impact.
RESULTS:
Over the study period, 919,458 HFMD cases were reported, with Shanghai (162,303) having the highest incidence and Tongling (5,513) having the lowest. Males were more commonly affected (male-to-female ratio, 1.49:1). The exposure-response relationship had an M-shaped curve, with two HFMD peaks occurring at 4 °C and 26 °C. The relative risk had two peaks at 1.30 °C (1.834, 95% CI: 1.204-2.794) and 31.4 °C (1.143, 95% CI: 0.901-1.451), forming an M shape, with the first peak higher than the second. The most significant impact of temperature on HFMD was observed between -2 °C and 18.1 °C. The concentration index (0.2463) indicated moderate concentration differences, whereas the Theil index (0.0418) showed low inequality in distribution.
CONCLUSION
The incidence of HFMD varied across cities, particularly with changes in temperature. Economically prosperous areas showed higher risks, indicating disparities. Targeted interventions in these areas are crucial for mitigating the risk of HFMD.
Female
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Humans
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Male
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China/epidemiology*
;
Cities/epidemiology*
;
Hand, Foot and Mouth Disease/transmission*
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Incidence
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Risk Factors
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Temperature
3.NFKBIE: Novel Biomarkers for Diagnosis, Prognosis, and Immunity in Colorectal Cancer: Insights from Pan-cancer Analysis.
Chen Yang HOU ; Peng WANG ; Feng Xu YAN ; Yan Yan BO ; Zhen Peng ZHU ; Xi Ran WANG ; Shan LIU ; Dan Dan XU ; Jia Jia XIAO ; Jun XUE ; Fei GUO ; Qing Xue MENG ; Ren Sen RAN ; Wei Zheng LIANG
Biomedical and Environmental Sciences 2025;38(10):1320-1325
4.Changing antimicrobial resistance profiles of Burkholderia cepacia in hospitals across China:results from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Chunyue GE ; Yunjian HU ; Xiaoman AI ; Yang YANG ; Fupin HU ; Demei ZHU ; Yingchun XU ; Xiaojiang ZHANG ; Hui LI ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Hong ZHANG ; Chun WANG ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Jilu SHEN ; Wenhui HUANG ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(5):557-562
Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1%(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5%,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3%(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1%)were isolated from sputum and respiratory secretions,followed by urine(10.7%)and blood samples(8.1%).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1%.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4%in the patients<18 years old to 20.6%in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.
5.Astragaloside Ⅳ attenuates pathological myocardial hypertrophy and fibrosis in mice via EGR1-SIRT1-PPARα-SCAD signaling pathway
Li-yuan QING ; Lan-ting LIU ; Qing-ping XU ; Huan PENG ; Yu-hong CAO ; Xue-diao PAN ; Si-gui ZHOU
Chinese Pharmacological Bulletin 2025;41(2):242-250
Aim To elucidate whether Astragaloside Ⅳcould ameliorate pathological myocardial hypertrophy and fibrosis via the EGR1-SIRT1-PPARα-SCAD signa-ling pathway in TAC mice.Methods After randomi-zing mice into groups,the Sham+AS-Ⅳ group and TAC+AS-Ⅳ group were intragastrically administered 20 mg·kg-1AS-Ⅳ once daily,whereas the Sham+NS group and TAC+NS group were given equivalent saline.Six weeks post-surgery,an evaluation of cardiac function was conducted,heart weight index was compu-ted,morphological alterations in heart were noted,vari-ations in collagen and myocardial hypertrophy indexes were analyzed,ATP content,free fatty acid content,hydroxyproline content,SCAD expression,and enzyme activity were measured,and an initial investigation into the protein expression of EGR1-SIRT1-PPARα-SCAD in myocardial tissues was undertaken.Results After AS-Ⅳ intervention,the heart weight index of TAC mice decreased(P<0.01),LVAWd,LVAWs,LVPWd and LVPWs values decreased(P<0.01,P<0.05),EF%and FS%values increased(all P<0.01),myocardial hypertrophy markers and collagen area decreased,FFA content,HYP content and collagen expression de-creased(all P<0.01),SCAD enzyme activity and ex-pression increased(P<0.01,P<0.05),and ATP content increased(P<0.01).The expression of EGR1 protein decreased,and the expression of SIRT1 and PPARα protein increased(all P<0.01).Conclu-sions AS-Ⅳ may improve fatty acid oxidation via the EGR1-SIRT1-PPARα-SCAD signaling pathway,thereby ameliorating pathological myocardial hypertrophy and fibrosis in TAC model mice.
6.Expert Consensus on the Ethical Requirements for Generative AI-Assisted Academic Writing
You-Quan BU ; Yong-Fu CAO ; Zeng-Yi CHANG ; Hong-Yu CHEN ; Xiao-Wei CHEN ; Yuan-Yuan CHEN ; Zhu-Cheng CHEN ; Rui DENG ; Jie DING ; Zhong-Kai FAN ; Guo-Quan GAO ; Xu GAO ; Lan HU ; Xiao-Qing HU ; Hong-Ti JIA ; Ying KONG ; En-Min LI ; Ling LI ; Yu-Hua LI ; Jun-Rong LIU ; Zhi-Qiang LIU ; Ya-Ping LUO ; Xue-Mei LV ; Yan-Xi PEI ; Xiao-Zhong PENG ; Qi-Qun TANG ; You WAN ; Yong WANG ; Ming-Xu WANG ; Xian WANG ; Guang-Kuan XIE ; Jun XIE ; Xiao-Hua YAN ; Mei YIN ; Zhong-Shan YU ; Chun-Yan ZHOU ; Rui-Fang ZHU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(6):826-832
With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.
7.Changing prevalence and antibiotic resistance profiles of carbapenem-resistant Enterobacterales in hospitals across China:data from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Wenxiang JI ; Tong JIANG ; Jilu SHEN ; Yang YANG ; Fupin HU ; Demei ZHU ; Yuanhong XU ; Ying HUANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yingchun XU ; Xiaojiang ZHANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Hong ZHANG ; Chun WANG ; Wenhui HUANG ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(4):445-454
Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43%(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38%,9.73%,and 8.47%,respectively.The prevalence of CRE strains in Escherichia coli was 1.99%.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)%,followed by blood(20.88±3.40)%and urine(18.40±3.45)%.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)%.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.
8.Changing distribution and antibiotic resistance profiles of the respiratory bacterial isolates in hospitals across China:data from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Ying FU ; Yunsong YU ; Jie LIN ; Yang YANG ; Fupin HU ; Demei ZHU ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Hong ZHANG ; Chun WANG ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Jilu SHEN ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE ; Wenhui HUANG
Chinese Journal of Infection and Chemotherapy 2025;25(4):431-444
Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6%of the isolates were Gram-negative bacteria and 17.4%were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)%and(94.0±0.1)%,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P<0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9%.The prevalence of penicillin-resistant S.pneumoniae was 1.4%.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8%and 41.3%,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7%,20.8%,9.4%,29.8%,and 73.3%,respectively.The prevalence of β-lactamase was 96.1%in Moraxella catarrhalis and 60.0%in Haemophilus influenzae.The H.influenzae isolates from children(<18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P<0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.
9.Investigation of tumor-suppressive mechanism of Guiqi Yiyuan Extract combined with cisplatin in Lewis lung cancer mice via TXNIP/NLRP3/Caspase-1/GSDMD pathway
Qiong-qiong GUO ; Wen-jie LI ; Jin-tian LI ; Jian-qing LIANG ; Ping TIAN ; Rong HU ; Xu-chao DONG ; Mei-hao XUE ; Long-xin XU
Chinese Traditional Patent Medicine 2025;47(9):2894-2901
AIM To investigate the tumor-suppressive mechanism of Guiqi Yiyuan Extract combined with cisplatin in Lewis lung cancer mice.METHODS Ten intact C57BL/6J mice were assigned to the blank group.Sixty additional mice were developed into Lewis lung cancer models bearing transplanted tumor and subsequently allocated into the model group,the cisplatin group(5 mg/kg),the high-dose Guiqi Yiyuan Extract group(6.6 g/kg),and the low-dose,medium-dose and high-dose Guiqi Yiyuan Extract combined with cisplatin group(1.6,3.3,6.6 g/kg+5 mg/kg),with 10 mice in each group.Mice in the blank and model groups received saline via daily gavage,while treatment groups were administered Guiqi Yiyuan Extract orally(once daily),and cisplatin injection intraperitoneally(once every other day).After 14 days of drug administration,mice were euthanized for endpoint analysis.The following assessments were conducted:general health status and body weight changes monitored throughout the study period;tumor excision and weighing for inhibition rate calculation;histopathological examination of tumors via hematoxylin-eosin(HE)staining;serum quantification of IL-1 β,IL-18 and HMGB1 by ELISA;ultrastructural analysis of tumor cell death using transmission electron microscopy(TEM);spatial localization of TXNIP and GSDMD-N in tumor sections via immunofluorescence(IF);and Western blot detection of TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD,GSDMD-N protein expressions in tumor tissues.RESULTS Compared to the model group,the cisplatin group and all combination therapy groups exhibited significant reduction in tumor weight(P<0.05)and increased tumor suppression rate;enhanced tumor tissue necrosis with characteristic pyroptotic morphology;elevated serum levels of IL-1β,IL-18 and HMGB1(P<0.05);and upregulated expressions of pyroptosis-associated proteins TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD and GSDMD-N(P<0.05).The high dose combination group demonstrated optimal therapeutic efficacy(P<0.05).CONCLUSION Guiqi Yiyuan Extract enhances cisplatin sensitivity,demonstrating synergistic anti-tumor effects in Lewis lung carcinoma-bearing mice.This combinatorial therapeutic effect likely involves modulation of the TXNIP/NLRP3/Caspase-1/GSDMD pathway.
10.Non-invasive model diagnostic efficacy assessment for liver fibrosis in patients with chronic hepatitis B combined with metabolic associated fatty liver disease
Yixuan ZHU ; Liang XU ; Youwen TAN ; Qinglei ZENG ; Guojun LI ; Weimao DING ; Fajuan RUI ; Xue BAI ; Leyao JIA ; Sisi ZHOU ; Qing XIE ; Junping SHI ; Jie LI
Chinese Journal of Hepatology 2025;33(9):852-861
Objective:To investigate the efficacy of fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet count ratio (APRI), liver stiffness value (LSM), and Agile 3+ score and their combined model in predicting advanced-stage liver fibrosis in patients with chronic hepatitis B (CHB) combined with metabolic-associated fatty liver disease (MAFLD).Methods:A multicenter retrospective cohort study was conducted on the BMOVE population.Nine hundred twenty CHB cases combined with MAFLD who underwent liver biopsy at seven medical centers in China from April 2006 to December 2023 were included. The patients were divided into advanced-stage liver fibrosis (159 cases) and non-advanced-stage liver fibrosis (761 cases) according to the Scheuer's scoring system.The area under the receiver operating characteristic curve (AUROC), decision curve, and calibration curve analysis were used to evaluate the efficacy of the firbrosis-4 index (FIB-4) score, NFS score, APRI index, LSM, and Agile 3+ score and their combined model in predicting advanced-stage fibrosis. The liver fibrosis grade of all patients was diagnosed by liver biopsy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each scoring model and combined model, as well as the proportion of correctly classified patients, were calculated based on different cutoff values.Results:AUROC analysis showed that Agile 3+ (0.814, 95% CI: 0.787-0.838) and LSM (0.805, 95% CI: 0.778-0.829) had similar accuracy and were superior to FIB-4 (0.721, 95% CI: 0.691-0.749), NFS (0.687, 95% CI: 0.656-0.716) and APRI ( 0.689, 95% CI: 0.658-0.718); however, HBV DNA level and HBV e antigen status had no effect on this outcome. Decision curve analysis showed that interventions based on LSM and Agile 3+ had provided higher net benefits compared with serological scores. Calibration curves showed that Agile 3+ had better predicitive accuracy than all other models. Agile 3+ had the highest PPV (0.54), minimal uncertainty interval (11.6%), and the highest proportion of correctly classified patients (76%); followed by LSM (PPV: 0.43, uncertainty interval: 15.5%, correct classification rate: 66%), and FIB-4 (PPV: 0.42, uncertainty interval: 26.1%, correct classification rate: 62.6%) in terms of identifying advanced-stage liver fibrosis. Combined model analysis demonstrated that FIB-4 combined with Agile 3+ had improved the correct classification rate and reduced the proportion of missed patients compared with FIB-4 combined with LSM. Conclusion:The Agile 3+ score is superior than LSM, FIB-4, NFS, and APRI index at identifying advanced-stage fibrosis in patients with CHB combined with MAFLD. This study supports the use of FIB-4 index combined with Agile 3+ for risk stratification in patients with CHB combined with MAFLD.

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