1.Fibroblast activation protein targeting radiopharmaceuticals: From drug design to clinical translation.
Yuxuan WU ; Xingkai WANG ; Xiaona SUN ; Xin GAO ; Siqi ZHANG ; Jieting SHEN ; Hao TIAN ; Xueyao CHEN ; Hongyi HUANG ; Shuo JIANG ; Boyang ZHANG ; Yingzi ZHANG ; Minzi LU ; Hailong ZHANG ; Zhicheng SUN ; Ruping LIU ; Hong ZHANG ; Ming-Rong ZHANG ; Kuan HU ; Rui WANG
Acta Pharmaceutica Sinica B 2025;15(9):4511-4542
The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.
2.Intercellular communication interference through energy metabolism-related exosome secretion inhibition for liver fibrosis treatment.
Mengyao ZHANG ; Huaqing JING ; Xinyi LIU ; Valentin A MILICHKO ; Yunsheng DOU ; Yingzi REN ; Zitong QIU ; Wen LI ; Weili LIU ; Xinxing WANG ; Nan LI
Acta Pharmaceutica Sinica B 2025;15(9):4900-4916
As activated hepatic stellate cells (aHSCs) play a central role in fibrogenesis, they have become key target cells for anti-fibrotic treatment. Nevertheless, the therapeutic efficiency is constrained by the exosomes they secrete, which are linked to energy metabolism and continuously stimulate the activation of neighboring quiescent hepatic stellate cells (qHSCs). Herein, an intercellular communication interference strategy is designed utilizing paeoniflorin (PF) loaded and hyaluronic acid (HA) coated copper-doped ZIF-8 (PF@HA-Cu/ZIF-8, PF@HCZ) to reduce energy-related exosome secretion from aHSCs, thus preserving neighboring qHSCs in a quiescent state. Simultaneously, the released copper and zinc ions disrupt key enzymes involved in glycolysis to reduce bioenergy synthesis in aHSCs, thereby promoting the reversion of aHSCs to a quiescent state and further decreasing exosome secretion. Therefore, PF@HCZ can effectively sustain both aHSCs and qHSCs in a metabolically dormant state to ultimately alleviate liver fibrosis. The study provides an enlightening strategy for interrupting exosome-mediated intercellular communication and remodeling the energy metabolic status of HSCs with boosted antifibrogenic activity.
3.Effects of aerobic exercise on endothelial progenitor cells function and the Akt/eNOS signaling pathway in type 2 diabetic rats
Jintao WU ; Yong SUN ; Yingzi LIANG ; Xiaozhe LIU
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(7):595-600
Objective:To investigate any effect of aerobic exercise on the functioning of endothelial progenitor cells (EPCs) and on the Akt/eNOS signaling pathway in type 2 diabetes.Methods:Forty-five 6-week-old Sprague-Dawley rats free of specific pathogens were randomly divided into a normal control group, a diabetic model group and an exercise group. Type 2 diabetes mellitus was induced in the model and exercise groups by feeding a high-fat diet and streptozotocin injection. After successful modeling, the exercise group underwent 8 weeks of non-weight-bearing swimming training after which blood was collected from their abdominal aortas to measure EPCs, serum nitric oxide and the level of vascular endothelial growth factor (VEGF). Bone marrow-derived EPCs were isolated from the rats′ femurs and tibias for in vitro culture. The cells′ tube formation capacity was assessed using Matrigel assays, while the expression of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) were determined using western blotting.Results:Compared with the normal group, the model group exhibited significantly reduced counts of EPCs in their peripheral blood. Serum NO and VEGF were also significantly lower, on average, and tube formation capacity was significantly impaired. p-Akt and p-eNOS protein expression were significantly downregulated. In contrast, the exercise group showed significantly increased EPC counts, elevated serum NO and VEGF levels, improved tube formation, and upregulated p-Akt and p-eNOS expression compared with the model group.Conclusions:Aerobic exercise improves EPC functioning in diabetic rats, and its mechanism may be associated with the regulation of the Akt/eNOS signaling pathway.
4.Effects of inspiratory muscle training on the autonomic nervous functioning and exercise capacity of patients with chronic obstructive pulmonary disease
Jian JIA ; Yingzi LIANG ; Xiaozhe LIU
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(6):519-523
Objective:To evaluate the effect of inspiratory muscle training on autonomic nervous function, respiratory muscle strength, lung function and exercise capacity in patients with chronic obstructive pulmonary disease (COPD).Methods:Sixty COPD patients were randomly divided into an observation group and a control group, each of 30. Both groups received routine rehabilitation management (pharmacotherapy, pursed-lip breathing exercises, and abdominal breathing training), but the observation group also received threshold-loaded inspiratory muscle training at 30% of their maximum inspiration pressure. The regimen was three sessions weekly over a 12-week period. Before and after the intervention, everyone′s lung function and respiratory muscle strength were measured with an electronic spirometer. The 6min walking test (6MWT) was also administered, with the subjects′ heart rate variability (HRV) recorded.Results:After the intervention, no significant change was observed among the control group in any of the measurements except in their average maximum inspiratory pressure and 6MWT distance. In the observation group there was a significant increase in their average maximum inspiratory pressure (97.0±12.8cmH 2O) and 6MWT distance, but a significant decrease in the average heart rate after the 6MWT. Conclusions:Twelve weeks of low-intensity inspiratory muscle training can significantly improve the respiratory muscle strength, functional exercise capacity and cardiac function of stable COPD patients, relieving their risk of cardiovascular disease.
5.Effects of inspiratory muscle training on the autonomic nervous functioning and exercise capacity of patients with chronic obstructive pulmonary disease
Jian JIA ; Yingzi LIANG ; Xiaozhe LIU
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(6):519-523
Objective:To evaluate the effect of inspiratory muscle training on autonomic nervous function, respiratory muscle strength, lung function and exercise capacity in patients with chronic obstructive pulmonary disease (COPD).Methods:Sixty COPD patients were randomly divided into an observation group and a control group, each of 30. Both groups received routine rehabilitation management (pharmacotherapy, pursed-lip breathing exercises, and abdominal breathing training), but the observation group also received threshold-loaded inspiratory muscle training at 30% of their maximum inspiration pressure. The regimen was three sessions weekly over a 12-week period. Before and after the intervention, everyone′s lung function and respiratory muscle strength were measured with an electronic spirometer. The 6min walking test (6MWT) was also administered, with the subjects′ heart rate variability (HRV) recorded.Results:After the intervention, no significant change was observed among the control group in any of the measurements except in their average maximum inspiratory pressure and 6MWT distance. In the observation group there was a significant increase in their average maximum inspiratory pressure (97.0±12.8cmH 2O) and 6MWT distance, but a significant decrease in the average heart rate after the 6MWT. Conclusions:Twelve weeks of low-intensity inspiratory muscle training can significantly improve the respiratory muscle strength, functional exercise capacity and cardiac function of stable COPD patients, relieving their risk of cardiovascular disease.
6.Effects of aerobic exercise on endothelial progenitor cells function and the Akt/eNOS signaling pathway in type 2 diabetic rats
Jintao WU ; Yong SUN ; Yingzi LIANG ; Xiaozhe LIU
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(7):595-600
Objective:To investigate any effect of aerobic exercise on the functioning of endothelial progenitor cells (EPCs) and on the Akt/eNOS signaling pathway in type 2 diabetes.Methods:Forty-five 6-week-old Sprague-Dawley rats free of specific pathogens were randomly divided into a normal control group, a diabetic model group and an exercise group. Type 2 diabetes mellitus was induced in the model and exercise groups by feeding a high-fat diet and streptozotocin injection. After successful modeling, the exercise group underwent 8 weeks of non-weight-bearing swimming training after which blood was collected from their abdominal aortas to measure EPCs, serum nitric oxide and the level of vascular endothelial growth factor (VEGF). Bone marrow-derived EPCs were isolated from the rats′ femurs and tibias for in vitro culture. The cells′ tube formation capacity was assessed using Matrigel assays, while the expression of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) were determined using western blotting.Results:Compared with the normal group, the model group exhibited significantly reduced counts of EPCs in their peripheral blood. Serum NO and VEGF were also significantly lower, on average, and tube formation capacity was significantly impaired. p-Akt and p-eNOS protein expression were significantly downregulated. In contrast, the exercise group showed significantly increased EPC counts, elevated serum NO and VEGF levels, improved tube formation, and upregulated p-Akt and p-eNOS expression compared with the model group.Conclusions:Aerobic exercise improves EPC functioning in diabetic rats, and its mechanism may be associated with the regulation of the Akt/eNOS signaling pathway.
7.Study on Influencing Factors of Nurses’ Willingness to Participate in Humanistic Nursing Training
Jianjing WANG ; Li MA ; Yilan LIU ; Wenjing ZHU ; Weiwei CHEN ; Yingzi LI ; Lifang REN ; Hongzhen XIE
Chinese Medical Ethics 2024;35(4):445-453
In order to understand nurses’ willingness to participate in humanistic nursing training and its influencing factors, and provide reference for managers to understand the current situation and improve nurses’ enthusiasm for humanistic nursing training. The convenience sampling method was used to investigate 23 707 nurses in 28 provinces (autonomous regions and municipalities directly under the central government) through a self-designed questionnaire distributed on the Internet. The results showed that 98.1% of nurses thought that participating in humanistic nursing related training was helpful to clinical work, but only 88.6% of the respondents were willing to participate in humanistic nursing training. Thirty factors were analyzed from four aspects of basic characteristics of individuals, cognitive relevant experience and organizational atmosphere. Fifteen factors had significant significance in binary Logistic regression analysis (P<0.05). Among them, the factors that had a positive impact on training willingness were: marriage, education, professional title, post establishment, agree with humanistic care is the basic duty of a nurse praised, experience of being praised at work, family support, rapport with patients, passion of colleagues to participate in training, sustained high-quality care demonstration activities, join the humanistic care related organization, hospital reimbursement of training expenses (OR value of 6.559~1.113, P<0.001). The OR value of humanistic nursing as a nurse’s responsibility was 6.559 and the 95%CI was 5.585~7.702. The factors that hindered nurses from participating in training were: work occupied most of time and energy, think humanistic nursing is abstract and difficult to understand, think the mastered humanistic knowledge and skills meet the needs of work (OR value of 0.657~0.722, P<0.001). Through the analysis, it is considered that nurses have a extremely consistent high recognition of the significance of humanistic nursing training, but their willingness to receive training is affected by many factors such as individual experience, cognitive attitude and organizational atmosphere. In order to realize nurses’ high recognition of humanistic nursing training to high enthusiasm of behavior, the aspects of individual cognition and organizational atmosphere must be discussed.
8.Study on the medication law of treatment for acute mastitis in Pu Ji Fang based on the ancient and modern medical record cloud platform
Shuang LIU ; Yingzi ZHANG ; Zongyou LI
International Journal of Traditional Chinese Medicine 2024;46(4):514-518
Objective:To analyze the medication characteristics and the rules of prescription for the treatment of acute mastitis in Puji Fang; To provide reference for the clinical treatment of acute mastitis in modern TCM. Methods:Prescriptions of the chapters of " Ruyong" and " Duru" contained in Pu Ji Fang? Fu Ren Zhu Ji Men were screened, and the prescription data were analyzed by using the ancient and modern medical record cloud platform V2.3.5 for drug frequency, properties, tastes, meridian tropism, and efficacy. Clustering analysis of high-frequency drugs and analysis of association rules were performed. Results:A total of 141 prescriptions were included, with 201 kinds of Chinese materia medica. The top ten drugs with the high frequency of use were Glycyrrhizae Radix et Rhizoma, Paeoniae Radix alba, Rhei Radix et Rhizoma, Angelicae Sinensis Radix, Astragali Radix, Olibanum, Trichosanthis Fructus, Ginseng Radix et Rhizoma, Scutellariae Radix, Gleditsiae Spina. The main property was cold, the main taste was sweet, the main meridian was spleen meridian, and the main efficacy was heat clearing and detoxification. Three types of high-frequency drugs could be obtained by clustering analysis, namely, Ginseng Radix et Rhizoma-Astragali Radix-Angelicae Sinensis Radix-Rhei Radix et Rhizoma, Scutellariae Radix-Paeoniae Radix alba-Glycyrrhizae Radix et Rhizoma, Trichosanthis Fructus-Olibanum-Gleditsiae Spina. Through correlation analysis of high-frequency drugs, it was found that there was a great correlation between Astragali Radix and Paeoniae Radix alba, Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma.Conclusions:The pathogenesis of acute mastitis in Pu Ji Fang is mainly damp-heat toxin and blood stasis, and deficiency of qi and blood. The treatment for strengthening healthy qi focuses on tonifying qi and blood of the liver and spleen, while the treatment for eliminating pathogenic factors focuses on removing dampness, clearing heat and toxin, resolving phlegm, dispersing stasis and removing blood stasis. In addition, according to the condition, the treatment will be increased or decreased with the disease.
9.Discussing the Staged Treatment of Progressive Fibrosing Interstitial Lung Disease Based on the Theory of "Opening-Closing-Pivoting"
Haoxiang ZHANG ; Jin'e WANG ; Xiao XIA ; Yanyi LIU ; Yujin DING ; Yingzi TIAN ; Kun XIA ; Guangxi LI
Journal of Traditional Chinese Medicine 2024;65(18):1882-1887
Progressive fibrosing interstitial lung disease (PF-ILD) has a complex etiology, and is classified as lung impediment stage, impediment-atrophy combination stage, and lung atrophy stage according to the different clinical manifestations during the progression of disease. Based on the theory of opening-closing-pivoting to analyse the characteristics of yin and yang disease mechanism and the idea of prescriptions in the three stages. For lung impediment stage, main as three-Yang fail to keep inside, disharmony between Ying qi (营气) and Wei qi (卫气), shaoyin impairment, treatment should use Mahuang (Ephedra sinica) and Guizhi (Neolitsea cassia) flexibly to form a formula, or choose pungent-dispersing formulas like Baidu Powder (败毒散) to move qi and save yang, and diffuse and disperse impediment pathogen, meanwhile combining saving-shaoyin medicinals like Fuzi (Aconitum carmichaelii) and Shudihuang (Radix Rehmanniae Praeparata) to reinforce healthy qi and dispel pathogen; for impediment-atrophy combination stage, rooted as yangming impairment and progressed by over-movement of qi, treatment should use Mahuang Shengma Decoction (麻黄升麻汤) to resolve and decrease over-activities, emphasis on both opening and closing, and improve impediment and atrophy; for lung atrophy stage with three-Yin in a bad condition simultaneously and poor prognosis, treatment should use modified Jinshui Liujun Decoction (金水六君煎) to consolidate qi and save yin, disperse phlegm and stasis, to improve the quality of life for patients with PF-ILD.
10.Microbial Diversity in Rhizosphere Soil of Gastrodia elata with Different Yields
Yingzi LUO ; Mingjin HUANG ; Dachang WANG ; Cheng LI ; Gang GUO ; Hongchang LIU ; Mingsheng ZHANG ; Zhi ZHAO ; Songlin RUAN ; Tingchi WEN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(1):133-140
ObjectiveTo analyze the microbial diversity in the rhizosphere soil of Gastrodia elata with different yields and explore the influence of soil microorganisms on the yield of G. elata. MethodThe experiment adopted the 16S DNA and ITS high-throughput sequencing technologies to study the diversity of the bacterial and fungal community in the rhizosphere soil of G. elata with high yield (GC) and low yield (DC). ResultProteobacteria, Firmicutes, and other unidentified Bacteria were dominant in the rhizosphere soil of G. elata. The dominant rhizosphere fungi were Ascomycota, Basidiomycota, and Mortierellomycota. There was no significant difference in microbial community abundance in the high-yield and low-yield rhizosphere soil of G. elata, but there was a significant difference in species composition. Thirty-eight microbes such as Bradyrhizobium, Schleiferilactobacillus, and Archaeorhizomyces were gathered in large numbers in the high-yield rhizosphere soil, and thirty microbes such as Fusarium, Coprinellus, and Nitrosotalea were gathered in large numbers in the low-yield rhizosphere soil. At the level of genus and species, there were six different species in the high-yield and low-yield rhizosphere soil of G. elata, among which Russula mariae, Archeaeorhizomyces, and Ilyonectria were gathered in the high-yield rhizosphere soil of G. elata, while Nitrosotalea, Coprinellus disserminatus, and Fusarium were gathered in the low-yield rhizosphere soil of G. elata. ConclusionThere are different microorganisms in the rhizosphere soil of G. elata with different yields, and it is speculated that these microorganisms are related to the yields of G. elata. The research results are expected to provide a vital theoretical basis for the follow-up study of the high yield of G. elata.

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