1.Ablation of macrophage transcriptional factor FoxO1 protects against ischemia-reperfusion injury-induced acute kidney injury.
Yao HE ; Xue YANG ; Chenyu ZHANG ; Min DENG ; Bin TU ; Qian LIU ; Jiaying CAI ; Ying ZHANG ; Li SU ; Zhiwen YANG ; Hongfeng XU ; Zhongyuan ZHENG ; Qun MA ; Xi WANG ; Xuejun LI ; Linlin LI ; Long ZHANG ; Yongzhuo HUANG ; Lu TIE
Acta Pharmaceutica Sinica B 2025;15(6):3107-3124
Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.
2.TSZAF monomer combination downregulates the Wnt/β-catenin signaling pathway and inhibits neutrophil recruitment to prevent lung cancer metastasis.
Pan YU ; Jialiang YAO ; Long ZHANG ; Yanhong WANG ; Xinyi LU ; Jiajun LIU ; Zujun QUE ; Yao LIU ; Qian BA ; Jiwei LIU ; Yan WU ; Jianhui TIAN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(9):1069-1079
Metastasis remains the primary cause of cancer-related mortality worldwide. Circulating tumor cells (CTCs) represent critical targets for metastasis prevention and treatment. Traditional Chinese medicine may prevent lung cancer metastasis through long-term intervention in CTC activity. Tiao-Shen-Zhi-Ai Formular (TSZAF) represents a Chinese medicine compound prescription utilized clinically for lung cancer treatment. This study combined three principal active ingredients from TSZAF into a novel TSZAF monomer combination (TSZAF mc) to investigate its anti-metastatic effects and mechanisms. TSZAF mc demonstrated significant inhibition of proliferation, migration, and invasion in CTC-TJH-01 and LLC cells, while inducing cellular apoptosis in vitro. Moreover, TSZAF mc substantially inhibited LLC cell growth and metastasis in vivo. Mechanistically, TAZSF mc significantly suppressed the Wnt/β-catenin signaling pathway and CXCL5 expression in lung cancer cells and tissues. Additionally, TAZSF mc notably reduced neutrophil infiltration in metastatic lesions. These findings indicate that TSZAF mc inhibits lung cancer growth and metastasis by suppressing the Wnt/β-catenin signaling pathway and reducing CXCL5 secretion, thereby decreasing neutrophil recruitment and infiltration. TSZAF mc demonstrates potential as an effective therapeutic agent for lung cancer metastasis.
Lung Neoplasms/genetics*
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Wnt Signaling Pathway/drug effects*
;
Animals
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Humans
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Drugs, Chinese Herbal/pharmacology*
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Mice
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Neoplasm Metastasis/prevention & control*
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Cell Proliferation/drug effects*
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Cell Line, Tumor
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Neutrophil Infiltration/drug effects*
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Down-Regulation/drug effects*
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Cell Movement/drug effects*
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beta Catenin/genetics*
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Apoptosis/drug effects*
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Mice, Inbred C57BL
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Male
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Neoplastic Cells, Circulating/drug effects*
3.Construction and Testing of Health LifeStyle Evidence (HLSE)
Chen TIAN ; Yong WANG ; Yilong YAN ; Yafei LIU ; Yao LU ; Mingyao SUN ; Jianing LIU ; Yan MA ; Jinling NING ; Ziying YE ; Qianji CHENG ; Ying LI ; Jiajie HUANG ; Shuihua YANG ; Yiyun WANG ; Bo TONG ; Jiale LU ; Long GE
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1413-1421
Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (
4.Method for Developing Patient Decision Aid in China
Yao LU ; Qian ZHANG ; Qianji CHENG ; Jianing LIU ; Mingyao SUN ; Jinling NING ; Jiajie HUANG ; Simeng REN ; Wenzheng ZHANG ; Yajie LIU ; Xiyuan DENG ; Jinhui TIAN ; Jie LIU ; Long GE
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1422-1431
To systematically construct a guideline to provide a methodological guide for researchers to develop patient decision aids. Through a literature review of international methodological guidance for developing patient decision aids, sorting out the similarities and differences in the processes and methods for developing patient decision aids, and combining them with the topic discussion of the working group, the initial guideline was drafted. A total of 13 guidances was included, with the initial version containing 3 phases, 13 steps, and 48 points. We invited 19 multidisciplinary domain experts for forming consensus. The final version of the guideline contains 3 phases, 11 steps, and 24 points. The guideline has great potential to guide the development of patient decision aids in China and is expected to fill the methodological gap in the field. In the future, several rounds of pilot testing of the guideline based on specific decision issues will be conducted, and the guideline will be further revised and improved.
5.Applications and Challenges of Adaptive Platform Trial
Yan MA ; Qianji CHENG ; Yao LU ; Jinling NING ; Long GE
Medical Journal of Peking Union Medical College Hospital 2024;15(5):1157-1164
Adaptive design, with advantages such as dynamically adjusting trial plans, reducing resource waste, and improving trial efficiency, has broken through the competitive situation of new drug development and gradually met the needs of clinical research. In recent years, the use of adaptive design in platform trials as an innovative research model has added impetus to new drug development. This article outlines the research progress, contents and characteristics, common design types, statistical analysis, and case interpretation of adaptive design, and introduces the concept, types, and applications of adaptive platform trials, with the hope of providing scientific reference for further exploration of clinical trials and new drug development.
6.Construction and Testing of Health LifeStyle Evidence (HLSE)
Chen TIAN ; Yong WANG ; Yilong YAN ; Yafei LIU ; Yao LU ; Mingyao SUN ; Jianing LIU ; Yan MA ; Jinling NING ; Ziying YE ; Qianji CHENG ; Ying LI ; Jiajie HUANG ; Shuihua YANG ; Yiyun WANG ; Bo TONG ; Jiale LU ; Long GE
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1413-1421
Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (
7.Method for Developing Patient Decision Aid in China
Yao LU ; Qian ZHANG ; Qianji CHENG ; Jianing LIU ; Mingyao SUN ; Jinling NING ; Jiajie HUANG ; Simeng REN ; Wenzheng ZHANG ; Yajie LIU ; Xiyuan DENG ; Jinhui TIAN ; Jie LIU ; Long GE
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1422-1431
To systematically construct a guideline to provide a methodological guide for researchers to develop patient decision aids. Through a literature review of international methodological guidance for developing patient decision aids, sorting out the similarities and differences in the processes and methods for developing patient decision aids, and combining them with the topic discussion of the working group, the initial guideline was drafted. A total of 13 guidances was included, with the initial version containing 3 phases, 13 steps, and 48 points. We invited 19 multidisciplinary domain experts for forming consensus. The final version of the guideline contains 3 phases, 11 steps, and 24 points. The guideline has great potential to guide the development of patient decision aids in China and is expected to fill the methodological gap in the field. In the future, several rounds of pilot testing of the guideline based on specific decision issues will be conducted, and the guideline will be further revised and improved.
8.Experts consensus on standard items of the cohort construction and quality control of temporomandibular joint diseases (2024)
Min HU ; Chi YANG ; Huawei LIU ; Haixia LU ; Chen YAO ; Qiufei XIE ; Yongjin CHEN ; Kaiyuan FU ; Bing FANG ; Songsong ZHU ; Qing ZHOU ; Zhiye CHEN ; Yaomin ZHU ; Qingbin ZHANG ; Ying YAN ; Xing LONG ; Zhiyong LI ; Yehua GAN ; Shibin YU ; Yuxing BAI ; Yi ZHANG ; Yanyi WANG ; Jie LEI ; Yong CHENG ; Changkui LIU ; Ye CAO ; Dongmei HE ; Ning WEN ; Shanyong ZHANG ; Minjie CHEN ; Guoliang JIAO ; Xinhua LIU ; Hua JIANG ; Yang HE ; Pei SHEN ; Haitao HUANG ; Yongfeng LI ; Jisi ZHENG ; Jing GUO ; Lisheng ZHAO ; Laiqing XU
Chinese Journal of Stomatology 2024;59(10):977-987
Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.
9.Preparation of traditional Chinese medicine metal complexes supramolecular hydrogel and its multiple biological activity evaluation
Lin-ying WU ; Wen-min PI ; Xiao-yu LIN ; Yao-zhi ZHANG ; Ji-hui LU ; Xue-mei HUANG ; Peng-long WANG
Acta Pharmaceutica Sinica 2024;59(5):1306-1312
The effect of different concentrations of glycyrrhizic acid (GA) and Zn2+ on the self-assembly of metal complexes was investigated by forming metal complexes, and the properties and assembly mechanisms of the formed carrier-free supramolecular hydrogel were characterised. Scanning electron microscopy (SEM) and zeta potential were used to characterise the microscopic morphology and stability of the GA-Zn complex hydrogel, which had spherical-like particles of about 1 μm with good stability; the rheometer was used to detect its materialistic properties, which showed excellent stability, self-healing property and reversibility; through
10.Clinical Characteristics and Risk Factors of Infection in Hospitalized Patients with Multiple Myeloma with New Generation Therapies
Li-Ping YANG ; Xin-Yi LU ; Xin-Wei WANG ; Qiong YAO ; Lin-Yu LI ; Jie ZHAO ; Shao-Long HE ; Wei-Wei TIAN
Journal of Experimental Hematology 2024;32(6):1790-1797
Objective:To evaluate the clinical characteristics and risk factors of infections occurring during hospitalization in patients with multiple myeloma (MM) treated with new generation therapies (including immuno-modulatory drugs,proteasome inhibitors and monoclonal antibodies).Methods:The clinical data were collected from 155 patients with multiple myeloma who were treated in Shanxi Bethune Hospital from March,2017 to March,2022 and were retrospectively analyzed.For this study,the following therapies were considered to be new generation therapies:lenalidomide,pomadomide,bortezomib,ixazomib,daratumumab. The clinical characteristics and risk factors of infection were analyzed.Results:A total of 155 patients were included in this study.The median follow-up time was 20 months.Of 155 patients with MM,242 infection episodes were identified.Among the 242 infections,the incidence of clinically defined infection (CDI)was the highest (186,76.86%),followed by microbiologically defined infection (MDI)in 50 cases (20.66%),and fever at unknown focus (FUF)in 6 cases (2.48%).35 cases (14.46%)of bacteria,10 cases (4.13%)of viruses,and 5 cases (2. 07%)of fungi were clearly infected.The most common site of infection was the lower respiratory tract in 90 cases (37.19%),the upper respiratory tract in 83 cases (34.30%),and the digestive tract in 27 cases (11.16%).All-cause mortality was 8.39%(13/155).In univariate analysis,there was a higher correlation between ISS stage Ⅲ,the number of treatment lines ≥2,frail and infected patients with multiple myeloma.In multivariate analysis,ISS stage Ⅲ(OR=2.96,95%CI:1.19-7.40,P=0.02),the number of treatment lines ≥2 (OR=2.91,95%CI:1.13-7.51,P=0.03)and frail (OR=3.58,95%CI:1.44-8.89,P=0. 01)were risk factors for infection in patients with multiple myeloma in the era of new drugs.Conclusion:Patients with multiple myeloma treated with new agents are prone to bacterial infection during hospitalization.ISS stage Ⅲ,lines of therapy(≥2)and frail were associated with high risk for infection.

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