1.Erratum: Author correction to "SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade" Acta Pharm Sin B 9 (2019) 304-315.
Mingxia ZHAO ; Wenjie GUO ; Yuanyuan WU ; Chenxi YANG ; Liang ZHONG ; Guoliang DENG ; Yuyu ZHU ; Wen LIU ; Yanhong GU ; Yin LU ; Lingdong KONG ; Xiangbao MENG ; Qiang XU ; Yang SUN
Acta Pharmaceutica Sinica B 2025;15(5):2810-2812
[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].
2.Construction and optimization of 1, 4-butanediamine biosensor based on transcriptional regulator PuuR.
Junjie LIU ; Minmin JIANG ; Tong SUN ; Xiangxiang SUN ; Yongcan ZHAO ; Mingxia GU ; Fuping LU ; Ming LI
Chinese Journal of Biotechnology 2025;41(1):437-447
Biosensors have become powerful tools for real-time monitoring of specific small molecules and precise control of gene expression in biological systems. High-throughput sensors for 1, 4-butanediamine biosynthesis can greatly improve the screening efficiency of high-yielding 1, 4-butanediamine strains. However, the strategies for adapting the characteristics of biosensors are still rarely studied, which limits the applicability of 1, 4-butanediamine biosensors. In this paper, we propose the development of a 1, 4-butanediamine biosensor based on the transcriptional regulator PuuR, whose homologous operator puuO is installed in the constitutive promoter PgapA of Escherichia coli to control the expression of the downstream superfolder green fluorescent protein (sfGFP) as the reporter protein. Finally, the biosensor showed a stable linear relationship between the GFP/OD600 value and the concentration of 1, 4-butanediamine when the concentration of 1, 4-butanediamine was 0-50 mmol/L. The promoters with different strengths in the E. coli genome were used to modify the 1, 4-butanediamine biosensor, and the functional properties of the PuuR-based 1, 4-butanediamine biosensor were explored and improved, which laid the groundwork for high-throughput screening of engineered strains highly producing 1, 4-butanediamine.
Biosensing Techniques/methods*
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Escherichia coli/metabolism*
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Promoter Regions, Genetic/genetics*
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Green Fluorescent Proteins/metabolism*
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Transcription Factors/genetics*
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Escherichia coli Proteins/genetics*
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Diamines/metabolism*
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Gene Expression Regulation, Bacterial
3.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.
4.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.
5.Research on the present situation of detection strategies for infectious markers related to transfusion transimission in China
Wei TAN ; Shengyan YING ; Ning CHENG ; Yujun LI ; Xiaoli CHEN ; Fang WANG ; Yang ZHANG ; Xiaojie LIU ; Lin BAO ; Yong DUAN ; Chen MA ; Chunlan LIU ; Dengfeng WANG ; Zhijun ZHEN ; Li LI ; Jian ZHANG ; Ranran LU ; Peng WANG ; Mingxia LI ; Xinli JIN ; Xiaobo CAI ; Mei YU ; Jianling ZHONG ; Lili ZHU ; Jianping LI
Chinese Journal of Experimental and Clinical Virology 2023;37(4):383-388
Objective:To analyze the detection strategy and basic detection situation of markers of infectious diseases transmitted by transfusion in blood testing laboratories of blood stations in China.Methods:Based on the data of practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021, the data on the testing strategies and the basic detection information of the markers for the transmission of infectious diseases through transfusion in the member laboratories of the practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021 were collected, and the situation of the selection for testing markers, testing strategy and the testing method and other relevant aspects were sorted out and analyzed by charts.Results:The selection of the testing markers was consistent, but HTLV testing item was added in some member laboratories. The detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously was adopted in 47 member blood stations; 3) NAT method was dominated by mini pool-NAT in member laboratories. The number of members adopting mini-pools of 8 (MP8)-NAT decreased from 17 in 2017 to 14 in 2021, while the number of members adopting mini-pools of 6 (MP6)-NAT increased from 13 in 2017 to 22 in 2021; Roche NAT system accounted for the largest proportion.Conclusions:In order to ensure blood safety and avoid missing detection, the blood stations still adopt the detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously; Meanwhile, in order to increase the NAT positive rate, the proportion of mini pool-NAT mainly decreased year by year despite its dominating role, while the proportion of individual donation-NAT increased year by year; NAT method is transiting from mini-pools of 8 (MP8) to mini-pools of 6 (MP6); The proportion of imported NAT system used in NAT laboratory is relatively large.
6.Comparison of Effect of Different Microbial Agents on Quality of Lycii Fructus Based on Multiple Index Components
Jia HE ; Youyuan LU ; Mingxia XIE ; Haixia SUN ; Tao WANG ; Jiahui XUE ; Wanliang HAO ; Hanqing WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(24):177-184
ObjectiveTo reveal the effects of different microbial agents on quality of Lycii Fructus by comparing the differences in the contents of multiple types of chemical components in Lycii Fructus after the application of different microbial agents. MethodTaking Ningqi No. 7 as experimental material, four microbial agents, namely Peiyuan combined with Xinterui(TP group), Trichoderma harzianum combined with Bacillus subtilis(BW group), Genwuyou(MT group) and Junyiduo(JYD group), were applied, and no microbial agents was used as the blank group(CK group). Then the contents of total phenolics, total flavonoids, saccharides, amino acids, nucleosides and bases, betaine and other components in Lycii Fructus were determined by ultraviolet spectrophotometry(UV), high performance liquid chromatography(HPLC) and ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS/MS), and the methods such as multiple comparisons, principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) were used to analyze the effect of different microbial agents on the quality of Lycii Fructus. ResultMicrobial agents had different effects on chemical components of Lycii Fructus. The content of total phenolics was the highest in the TP group, and it varied significantly from the CK group(P<0.05). The total flavonoid content was the highest in the BW group, followed by the TP group. Both polysaccharide and alduronic acid contents were the highest in the JYD group. Betaine content in the TP and BW groups were significantly higher than that in the CK group(P<0.05). For the determined 23 kinds of amino acids, most of them were the lowest in the JYD group, and the highest in the MT group, while the nucleoside bases were higher in the MT and BW groups. It indicated that Lycii Fructus from different treatment groups could be distinguished clearly based on the determined 45 chemical components. The result of PLS-DA showed that the major differential components in each group were polysaccharides, glucose, fructose, betaine, alduronic acid, asparagine, sucrose, threonine, total flavonoids, alanine and total phenolics. The results of PCA composite scores based on the main differential components showed that composite scores of chemical components in each group were BW group>TP group>MT group>CK group>JYD group. ConclusionThe application of microbial agents of BW, TP and MT can promote the quality improvement of Lycii Fructus, and the application of JYD can promote the accumulation of polysaccharides and alduronic acid to a certain extent, but the overall effect on the quality of Lycii Fructus is not clear. This study lays the foundation for the green and healthy development of Lycii Fructus industry.
7.Sorting nexin 3 exacerbates doxorubicin-induced cardiomyopathy via regulation of TFRC-dependent ferroptosis.
Wenjing YU ; Yuehuai HU ; Zhiping LIU ; Kaiteng GUO ; Dinghu MA ; Mingxia PENG ; Yuemei WANG ; Jing ZHANG ; Xiaolei ZHANG ; Panxia WANG ; Jiguo ZHANG ; Peiqing LIU ; Jing LU
Acta Pharmaceutica Sinica B 2023;13(12):4875-4892
The clinical utilization of doxorubicin (Dox) in various malignancies is restrained by its major adverse effect: irreversible cardiomyopathy. Extensive studies have been done to explore the prevention of Dox cardiomyopathy. Currently, ferroptosis has been shown to participate in the incidence and development of Dox cardiomyopathy. Sorting Nexin 3 (SNX3), the retromer-associated cargo binding protein with important physiological functions, was identified as a potent therapeutic target for cardiac hypertrophy in our previous study. However, few study has shown whether SNX3 plays a critical role in Dox-induced cardiomyopathy. In this study, a decreased level of SNX3 in Dox-induced cardiomyopathy was observed. Cardiac-specific Snx3 knockout (Snx3-cKO) significantly alleviated cardiomyopathy by downregulating Dox-induced ferroptosis significantly. SNX3 was further demonstrated to exacerbate Dox-induced cardiomyopathy via induction of ferroptosis in vivo and in vitro, and cardiac-specific Snx3 transgenic (Snx3-cTg) mice were more susceptible to Dox-induced ferroptosis and cardiomyopathy. Mechanistically, SNX3 facilitated the recycling of transferrin 1 receptor (TFRC) via direct interaction, disrupting iron homeostasis, increasing the accumulation of iron, triggering ferroptosis, and eventually exacerbating Dox-induced cardiomyopathy. Overall, these findings established a direct SNX3-TFRC-ferroptosis positive regulatory axis in Dox-induced cardiomyopathy and suggested that targeting SNX3 provided a new effective therapeutic strategy for Dox-induced cardiomyopathy through TFRC-dependent ferroptosis.
8.SWOT analysis of influenza vaccination promotion of primary care staff based on the perspective of the supplier, customer, and management
Bo SUN ; Jiandong ZHENG ; Shengyang ZHANG ; Mingxia LU ; Heng YUAN ; Junren WANG ; Jincheng LI ; Jinfeng SU ; Mu LI ; Zhifeng WANG
Chinese Journal of Epidemiology 2022;43(6):953-959
Objective:To analyze the situation of influenza vaccination among primary healthcare workers, find out the problems, and explore the strategies and measures to promote influenza vaccination among grass-roots medical staff.Methods:From April to May 2021, key insider interviews and literature research were carried out based on the perspectives of influenza vaccine suppliers (influenza vaccine manufacturers), consumers (primary medical institutions and primary healthcare workers), and managers (governments at all levels, health administrative departments and disease prevention and control departments). The SWOT (strengths, weaknesses, opportunities, and threats) analysis technique was used to comprehensively evaluate the current situation of influenza vaccination among grass-roots healthcare workers, and a SWOT analysis matrix was established.Results:Influenza vaccination of grass-roots healthcare workers have advantages and opportunities, including primary medical and health institutions' vital influenza vaccination accessibility, influenza vaccine safety is higher, COVID-19 outbreak improves the public awareness of respiratory infectious diseases and vaccine production enthusiasm, coronavirus vaccination has strengthened the capacity of the vaccine distribution system. There are also disadvantages and threats such as the high price of influenza vaccine, insufficient supply, low awareness of influenza vaccine vaccination among grass-roots healthcare workers, lack of demand assessment mechanism on influenza vaccine, poor vaccine deployment, structural imbalance in vaccine supply in different areas, and severe vaccine waste. SWOT analysis matrix of the influenza vaccination status of grass-roots healthcare workers was established, forming dominant opportunity (SO) strategy, dominant threat (ST) strategy, inferior opportunity (WO) strategy, and inferior threat (WT) strategy.Conclusion:Measures should be taken by the supplier, the demand—side, and the management side to improve the influenza vaccine coverage rate of primary healthcare workers, but the emphasis should be on the coordination and management of the management side.
9.Investigation on the knowledge of pediatric nurses about intravenous infusion therapy
Xuhong WU ; Mingxia DUAN ; Lu WANG ; Yu GUO ; Jianli WANG ; Xin LIANG ; Qian DAI ; Yu CAO ; Linqi ZHANG
Chinese Journal of Modern Nursing 2020;26(1):26-31
Objective:To explore the knowledge of pediatric nurses about intravenous infusion therapy, find the problems, and provide a reference for managers to provide targeted training.Methods:In this multicenter cross-sectional study, the nurses on duty were selected from 43 hospitals under the medical alliance of Beijing Children's Hospital by convenient sampling from July 24th to 31st, 2018. The self-made questionnaires were used in this study, and data were collected online through wjx.cn. The questionnaires were developed by 4 veteran venous infusion therapists according to the Infusion Therapy Standards of Practice (2016 ) as well as the Technical Standards for Intravenous Therapy Nursing Issued by the National Health Commission of the People's Republic of China in 2014. The questionnaire mainly included three parts. Part I was the basic information of the respondent subjects and hospitals; Part II was the knowledge of the subjects about domestic standards for infusion therapy and Infusion Therapy Standards of Practice; and Part III the knowledge of the subjects about infusion therapy operations and maintenance as well as the current status of infusion therapy in their departments. SPSS 17.0 was used for statistical analysis. Results:A total of 8 405 pediatric nurses were investigated in this study. The average knowledge of infusion therapy was (11.72±2.41), and the pass rate was 54.8%. The survey showed that nurses performed well in selecting infusion tools and puncture sites according to the nature of the drug, evaluating the patient and treatment plan before infusion therapy, the sealing method of peripheral vein indwelling needles, and treatment methods when resistance was encountered or no blood was returned in suction. The univariate analysis revealed that the level of the hospital, whether the hospital had a dosing center and an infusion therapy group, the nurse's education, job title, working years, position, and whether to teach young nurses were the main influencing factors to nurses' knowledge about infusion therapy ( P<0.05) . The results of Logistic regression analysis showed that whether the hospital had a dosing center and a infusion therapy group, and the nurse's education background, title, working years, position, and teaching were the main influencing factors for the nurse's knowledge of infusion therapy ( P<0.05) . Conclusions:Pediatric nurses have insufficient knowledge about infusion therapy. They need to be further trained in the basics of infusion therapy, especially in the correct use of infusion tools, the proper selection of puncture sites, and catheter maintenance.
10.SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade.
Mingxia ZHAO ; Wenjie GUO ; Yuanyuan WU ; Chenxi YANG ; Liang ZHONG ; Guoliang DENG ; Yuyu ZHU ; Wen LIU ; Yanhong GU ; Yin LU ; Lingdong KONG ; Xiangbao MENG ; Qiang XU ; Yang SUN
Acta Pharmaceutica Sinica B 2019;9(2):304-315
Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both and . However, whether SHP099-mediated SHP2 inhibition retards tumor growth anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099. Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system. SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8IFN- T cells and the upregulation of cytotoxic T-cell related genes including , which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and anti-PD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growth in two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.

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