1.Astrocyte FGF7/FGFR2 autocrine signaling mediates neuroinflammation and promotes MPTP-induced degeneration of dopaminergic neurons.
Xin SUN ; Yueping WANG ; Yajie ZHANG ; Ruixue HAN ; Min WANG ; Jing ZHANG ; Ting SUN ; Yang LIU ; Gang HU ; Lei CAO ; Ming LU
Acta Pharmaceutica Sinica B 2025;15(9):4730-4750
Reactive astrocytes, which exhibit a correlation with the degeneration of dopaminergic neurons, are present in a considerable number during the progression of Parkinson's disease (PD). However, the underlying factors shaping astrocyte reactivity and neuroinflammation in PD remain inadequately elucidated. Here, we demonstrate that fibroblast growth factor 7 (FGF7)/FGF receptor 2 (FGFR2) autocrine signaling intensifies astrocyte reactivity and inflammation. Genetic deletion of Arrb2, β-Arrestin2 encoding gene, led to escalated astrocyte reactivity in MPTP-treated mice, which was further substantiated in astrocyte-specific Arrb2 knockdown mice. RNA sequencing profiling of Arrb2 knockout astrocytes identified Fgf7 as a critical effector of astrocyte reactivity. Subsequently, conditional knockdown of Fgf7 and its receptor Fgfr2 in astrocytes elicited advantageous effects for MPTP-treated mice by restraining the inflammatory phenotypic transition of reactive astrocytes. Furthermore, deletion of astrocytic Fgf7 mitigated MPTP-induced pathology in Arrb2 knockout mice. Mechanistically, STAT1 was distinguished as the transcription factor suppressing Fgf7 expression, while β-Arrestin2 counteracted the proteasomal degradation of STAT1 by binding to RNF220, an E3 ubiquitin ligase for STAT1. More importantly, selectively engaging dopamine D2 receptor (Drd2)/β-Arrestin2-biased signaling using the agonist UNC9995 exhibited therapeutic potential in MPTP-treated mice via moderation of astrocytic FGF7 production, thereby restoring balance in astrocyte reactivity. Collectively, our study bridges a crucial knowledge gap by elucidating the novel functions of FGF family members within the central nervous system, particularly within the context of PD. The autocrine signaling of FGF7/FGFR2 represents a novel mechanism and a potential druggable target for modulating astrocyte-derived inflammation.
2.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.
3.Exploration of Therapeutic Effect of Wujiwan on Inflammatory Bowel Disease in Rats Based on PPARγ Signaling Pathway and T-cell Immunoregulation
Shiyun GUO ; Yuxuan GUO ; Yi SUN ; Xiaoxin ZHU ; Yujie LI ; Ying CHEN ; Qing YANG ; Yajie WANG ; Qi LI ; Xiaogang WENG ; Zhihao DENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):237-245
ObjectiveThis study explores the efficacy and pharmacological mechanism of Wujiwan in rats with inflammatory bowel disease (IBD) from the perspectives of the peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway and T-cell immunity, providing reference for the treatment of IBD with traditional Chinese medicine. MethodThe study involved administering 2,4,6-trinitrobenzenesulfonic acid (TNBS) enemas to 35 rats to induce acute IBD. After 24 hours, the animals were divided into the following groups: normal group, model group, Wujiwan treatment group, and positive drug control group. Each group received gastric gavage for 8 consecutive days before the rats were dissected to compare the disease activity index (DAI) of the rat colon tissue, the colon mucosal damage index (CMDI), and the spleen index. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of interleukin-1β (IL-1β), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in the serum. Quantitative real-time polymerase chain reaction (Real-time PCR) was used to determine the mRNA expression levels of T-bet (T-box expressed in T cells) and Gata3 (Gata-binding protein-3) in the colon tissue. Western blot analysis was conducted to detect the protein expression levels of PPARγ, T-bet, and nuclear factor-κB p65 (NF-κB p65) in the rat colon. ResultThe rat model of IBD was successfully established. Compared with the model group, the Wujiwan treatment group showed reduced DAI, CMDI, and spleen index, decreased content of TNF-α in the serum(P<0.01), significantly increased content of IL-10(P<0.01), and elevated mRNA content of T-bet and Gata3(P<0.05) in the colon tissue. The expression of PPARγ protein was augmented(P<0.05), and the expression of T-bet and NF-κB p65 protein was decreased(P<0.05,P<0.01). ConclusionWujiwan activates or upregulates PPARγ expression in IBD rats to inhibit the generation of pro-inflammatory factors, participates in the inflammatory immune process, and alleviates inflammatory reactions. Its mechanism may involve regulating the NF-κB pathway through PPARγ, enhancing Th2 cell transcription expression, and reducing Th1 cell transcription.
4.A Review of Theoretical Research on Interpretation of Scientific Connotation of Compatibility of Traditional Chinese Medicine Compounds
Shiyun GUO ; Zhihao DENG ; Yan LI ; Yuxuan GUO ; Xiaoxin ZHU ; Yujie LI ; Ying CHEN ; Qing YANG ; Yi SUN ; Yajie WANG ; Qi LI ; Weiyan CAI ; Xiaogang WENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):338-344
Traditional Chinese medicine (TCM) has a long history of application in China and has consistently played a vital role in treating diseases and saving lives. TCM prescriptions (compounds) constitute the primary form of clinical TCM treatment and significantly differ from western medicine (chemicals) due to the diverse composition and chemical constituents of TCM (compounds). Nevertheless, the potential multi-component, multi-target, and multi-pathway action characteristics of TCM prescriptions also demonstrate their possible (complementary) therapeutic advantages when compared with single-component chemical drugs. Therefore, driven by the development of modern science and technology and the demands of the modernization and internationalization of TCM, modern theories regarding the complexity of TCM prescription effects have been continuously proposed: Different from the abstract language of traditional prescription theory, the modern TCM prescription theory is more inclined to illustrate the connotation of prescription compatibility concretely and vividly from an experimental and scientific perspective. In this paper, new theories on the complexity of TCM prescriptions proposed in recent years are summarized to provide research references and ideas for the greater role of TCM prescriptions and a better scientific understanding.
5.Dynamic expression of fibroblast growth factor receptors 1 and 2 in mouse kidney development
Shuangling BO ; Taifang MA ; Huijian BAI ; Yutian YANG ; Yajie SUN ; Xinchen ZHAO
Chinese Journal of Tissue Engineering Research 2024;28(25):4018-4021
BACKGROUND:The temporal and spatial expression of fibroblast growth factor receptors 1 and 2 remains a controversial issue during kidney development,so the relationship between them and kidney development remains unclear. OBJECTIVE:To observe the dynamic expression of fibroblast growth factor receptors 1 and 2 during kidney development of mice,and to investigate the relationship between them and kidney development. METHODS:The kidneys of fetal mice[embryotic days(E)12,14,16,and 18]and neonatal mice[neonatal days(N)1,3,7,14,24,and 40]were selected to examine the temporal and spatial expression of fibroblast growth factor receptors 1 and 2 by immunohistochemistry method in kidney tissues,and quantitative analysis was performed using western blot assay. RESULTS AND CONCLUSION:(1)Immunohistochemistry showed that fibroblast growth factor receptor 1 was mainly localized in metanephric tissue surrounding the tip of the ureteral bud at E12.Subsequently,fibroblast growth factor receptor 1 was expressed in immature renal corpuscles at various stages,some distal convoluted tubules and capillary loops.The positive site was mainly concentrated in the generative region.Fibroblast growth factor receptor 2 was initially expressed in both ureteral buds and metanephric tissue.Fibroblast growth factor receptor 2 was localized in immature renal corpuscles,distal tubules,collecting ducts and thin segments of medullary loops with kidney development.However,the expression of renal corpuscles was weak.(2)Stereology and western blot assay showed that the expression of fibroblast growth factor receptor 1 was high before birth and gradually decreased after birth,while the expression was very low after N7 day.The expression level of fibroblast growth factor receptor 2 increased gradually with the kidney development and tended to be stable after N7 day.(3)The results exhibit that fibroblast growth factor receptors 1 and 2 are expressed spatially and temporally during kidney development.It is speculated that fibroblast growth factor receptors 1 and 2 may influence nephron development and maturation,and fibroblast growth factor receptor 2 is critical during the formation of ureteral buds and morphology.
6.Cancer-related fatigue in patients with advanced malignant tumours:current status and influencing factors
Pei WANG ; Chao SUN ; Huixiu HU ; Shaohua GONG ; Yajie ZHAO ; Shengmiao MA
Modern Clinical Nursing 2024;23(1):8-13
Objective To investigate the status quo of cancer-related fatigue(CRF)in patients with advanced malignant tumours during anti-tumour treatment,and explore the influencing factors so as to provide a reference for nursing intervention.Methods Between January and August 2022,a total of 279 patients with advanced malignant tumours who received anti-tumour therapies in the Department of Oncology of a general hospital in Beijing were selected as study subjects using convenience sampling method.General data questionnaire,cancer fatigue scale,chemotherapy-related gastrointestinal symptoms inventory,and nutritional risk screening 2002 were used for the investigation.Logistic regression analysis was conducted to determine the influencing factors of cancer-related fatigue.Results Toally 279 patients finished the study.A total of 204(73.12%)patients had cancer-related fatigue.Binary logistic regression analysis showed that BMI,education,monthly family income and diabetes were the influencing factors in cancer-related fatigue(all P<0.05).Conclusions The incidence of cancer-related fatigue is high in patients with advanced malignant tumours during anti-tumour therapy.Low BMI,poor education,low monthly family income and diabetes are the risk factors in cancer-related fatigue.Targeted interventions should be implemented based on the risk factors so as to reduce the incidence of cancer-related fatigue.
7.Current situation and training demands for geriatric nursing ability of clinical nursing teachers
Chao SUN ; Yajie ZHAO ; Huixiu HU ; Lili WEI
Chinese Journal of Medical Education Research 2024;23(2):161-168
Objective:To investigate the current situation of geriatric nursing ability of clinical nursing teachers and analyze the influencing factors, and to identify demands of geriatric nursing training.Methods:From May to June 2023, a cross-sectional study was conducted among 2 408 clinical nursing teachers in 50 tertiary hospitals from 9 provinces and cities in East China, South China, Central China, North China, and Southwest China using the general information questionnaire, Geriatric Nursing Competence Scale for Clinical Nurses, and Geriatric Nursing Training Demands Questionnaire.Results:Among the clinical nursing teachers surveyed, there were 269 (11.17%), 938 (38.95%), and 1 201 (49.88%) teachers at low, medium, and high levels of geriatric nursing ability, respectively. The results of multinomial Logistic regression analysis showed that age, years of working in geriatric nursing, geriatric nursing related training, satisfaction with clinical nursing work, and interest in geriatric nursing work were common influencing factors in the low and medium level groups ( P<0.05), and professional title was a specific influencing factor in the medium level group ( P<0.05). The top three demands of geriatric nursing training content were geriatric nursing service model, knowledge of chronic disease management, and comprehensive geriatric assessment techniques. The top three demands of training forms were live streaming, field visits, and offline lectures. Conclusions:For clinical nursing teachers, demand-oriented geriatric nursing training should be strengthened, and attention should be paid to the satisfaction and interest in nursing work, so as to improve the teachers' geriatric nursing ability and strengthen the level of geriatric service.
8.Investigation and analysis of external radiation dose and physical and mental health status of radiation workers in medical institutions
Dinghao JI ; Yezhong YANG ; Na LI ; Xiadong WANG ; Zhen SUN ; Rui ZHANG ; Yajie NAN
Chinese Journal of Radiological Health 2024;33(6):659-666
Objective To investigate the external radiation doses and occupational health examination data of radiation workers in medical institutions in Zhangjiagang City, China, explore the effects of long-term exposure to low-dose ionizing radiation on their health, and provide a reference for occupational health monitoring. Methods The radiation workers of medical institutions in Zhangjiagang City were selected as the research subjects. Their personal radiation doses and occupational health examination data were collected. A scale was used for mental health survey. The data were analyzed according to different clinical characteristic groups. Results During the 5-year period from 2019 to 2023, the average annual radiation dose received by radiation workers in medical institutions in Zhangjiagang City was 0.21 mSv/year. There were significant differences in the average annual radiation dose across these years and radiation workers with different occupations. The results of occupational health examinations showed significant difference in the total abnormal detection rate among these years (P < 0.01). There were significant differences in the abnormal rates of blood pressure, blood routine, and electrocardiogram across these years (P < 0.05). There were significant differences in the abnormal rate of routine blood test in radiation workers with different sexes, years of service, and radiation occupations (P < 0.01). There were significant differences in the abnormal rate of blood pressure in radiation workers with different sexes, ages, and years of service (P < 0.01). The mental health survey showed significant differences between the radiation and the non-radiation groups in terms of occupational stress, anxiety score, and depression score (P < 0.05). Conclusion Long-term low-dose ionizing radiation may have adverse effects on the physical and mental health of radiation workers, and it is necessary to strengthen the occupational health examination and radiation protection of radiation workers.
9.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.
10.The impact of life behaviors on the rapid cognitive decline in the short term among community-dwelling elderly with mild cognitive impairment
Huixiu HU ; Chao SUN ; Yajie ZHAO ; Xiang LI ; Lei LI
Chinese Journal of Nursing 2024;59(21):2571-2578
Objective To analyze the impact of different lifestyle behaviors on the rapid decline in cognitive function within 6 months among the elderly with mild cognitive impairment(MCI)in the community.Methods From March 2023 to January 2024,a convenient sampling method was used to select elderly people with MCI from 2 community health service centers of Beijing as the research subjects.They were followed up for 6 months,and the data on general information,life behaviors,and changes in cognitive function were collected.They were divided into a cognitive decline group and a non-decline group based on whether there were reliable changes in clinical cognitive function.Logistic regression was used to analyze the independent influencing factors of short-term cognitive decline in MCI elderly.Results A total of 385 MCI elderly people were successfully followed up in this study,and 113(29.4%)showed cognitive decline.Logistic regression analysis revealed that life behaviors such as frequent passive cognitive activities,depressive symptoms,and poor sleep quality are independent risk factors for rapid cognitive decline in elderly individuals with MCI over a short period(P<0.05).Conversely,higher educational levels and good social activities are protective factors(P<0.05).Conclusion The incidence of rapid cognitive decline is relatively high among MCI elderly people in the community.We should actively guide MCI elderly people to establish healthy lifestyle behaviors,such as engaging in social activities,reducing passive cognitive activities,maintaining a good psychological state,and ensuring good sleep quality,so as to delay or even reverse their cognitive decline.

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