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.Influencing factors of exercise compliance in elderly patients with cognitive impairment: a Meta-synthesis of qualitative research
Yajie ZHAO ; Chao SUN ; Huixiu HU ; Jianni QU ; Jie LIU
Chinese Journal of Modern Nursing 2024;30(3):281-290
Objective:To integrate qualitative research on the influencing factors of exercise compliance in elderly patients with cognitive impairment.Methods:The research is a Meta-synthesis of qualitative research. Qualitative research on the influencing factors of exercise compliance in elderly patients with cognitive impairment were electronically searched on PubMed, Embase, Web of Science, CINAHL, Cochrane Library, China National Knowledge Infrastructure, WanFang Data, VIP, and SinoMed. The search period was from the establishment of the database to April 25, 2023. Two researchers independently evaluated the literature using the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center (2016 edition). The aggregative integration method was used to integrate the results.Results:A total of 16 articles were included, and 54 research results were extracted. These results were reorganized into seven categories and integrated into three outcomes, namely the personal factors that affected the exercise compliance of elderly patients with cognitive impairment including intrinsic motivation factors, physical and cognitive function factors, and psychological factors, social and interpersonal factors that affected exercise compliance in elderly patients with cognitive impairment including exercise team and caregiver factors, environmental factors that affected exercise compliance in elderly patients with cognitive impairment including social and natural environments factors.Conclusions:The exercise compliance of elderly patients with cognitive impairment is influenced by multiple factors. Medical and nursing staff should enhance patients' perception and belief in the benefits of exercise, pay attention to patients' psychological experience, establish a comprehensive support system to evaluate and develop personalized exercise plans, comprehensively evaluate the exercise environment and create a good exercise atmosphere to improve patients' enthusiasm for exercise.
3.A re-evaluation of the effectiveness of exercise interventions in patients with amyotrophic lateral sclerosis
Jing SHAN ; Yajie MIAO ; Jia LIU ; Jinju SUN ; Xue MENG ; Mengxue YANG
Chinese Journal of Modern Nursing 2024;30(28):3852-3858
Objective:To re-evaluate the effectiveness of exercise interventions in patients with amyotrophic lateral sclerosis (ALS) by conducting a systematic review and provide insights for the implementation and continuous improvement of exercise intervention strategies.Methods:A comprehensive search was conducted across databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, Embase, Cochrane Library, Web of Science, CINAHL, Campbell Collaboration, and the Joanna Briggs Institute Evidence-Based Health Care Center Database. The search covered literature from the inception of the databases until December 19, 2023. Two researchers trained in evidence-based nursing independently screened the literature. The methodological quality of the included studies was assessed using the AMSTAR 2 tool, and the quality of evidence was graded using the GRADE system.Results:Eight systematic reviews were included. The AMSTAR 2 evaluation revealed one review of moderate quality, six of low quality, and one of very low quality. GRADE assessment of 33 outcome indicators showed that one piece of evidence was of moderate quality, 24 were of low quality, and eight were of very low quality.Conclusions:Exercise interventions may improve overall functional outcomes in ALS patients without exacerbating fatigue. However, due to the limitations in the quantity and quality of the included studies, further large-scale, high-quality randomized controlled trials are needed to verify the effects of exercise interventions in ALS patients.
4.Application of transtheoretical model on promoting motor behavior among older adults in the community: a scoping review
Jie GAO ; Huixiu HU ; Chao SUN ; Yajie ZHAO ; Huanhuan LUO ; Yuqing HAO
Chinese Journal of Modern Nursing 2024;30(32):4348-4358
Objective:To carry out a scoping review on characteristics and effects of intervention program for promoting motor behavior among older adults in the community based on transtheoretical model (TTM), so as to explore the mechanism and connotation of TTM guiding strategy selection in the intervention program.Methods:The literature on the intervention program for promoting motor behavior among older adults in the community based on TTM was systematically searched in PubMed, Embase, CINAHL, Cochrane Library, PsycINFO, China National Knowledge Infrastructure and Wanfang Data. The search period was from database establishment to October 11, 2023. Two researchers conducted a summary and data analysis of the included literature.Results:A total of 15 articles were included, and the intervention framework included two types according to behavior change stages and behavior change patterns. The intervention strategy mainly included 17 items, such as emphasizing the benefits of exercise and drawbacks of no-exercise, establishing family support relationships, sharing exemplary experiences, rewarding, setting reminders, and signing commitments. The intervention strategies mainly involved 14 forms such as health lectures, one-on-one communication, exercise commitment letters, exercise logs, group communication meetings, and material/honor. The outcome measures consisted of feasibility (safety, retention, attendance, satisfaction) and effectiveness (exercise compliance, behavioral stage changes, physical function, self-efficacy, decision balance and so on) .Conclusions:The stages of change in TTM can guide the design of intervention frameworks for promoting motor behavior among older adults in the community, and the change program can guide the intervention strategies and design of application forms. The characteristic of the TTM based intervention program for promoting motor behavior among older adults in the community is that it contains intervention strategies that are suitable for each stage of behavior, and has short-term effectiveness and feasibility in terms of results. It is necessary to further clarify the details of the intervention program to explore its long-term effectiveness, and conduct follow-up.
5.Predictive value of olfactory function for cognitive decline in older adults with mild cognitive impairment
Huixiu HU ; Chao SUN ; Yajie ZHAO ; Meijuan LI ; Ying DENG ; Linzhi ZHANG
Chinese Journal of Modern Nursing 2024;30(32):4359-4365
Objective:To analyze the early predictive value of olfactory function for cognitive decline in older adults with mild cognitive impairment (MCI) .Methods:From March 2023 to January 2024, convenience sampling was used to select 385 older adults with MCI from two community health service centers in Dongcheng District and Fengtai District of Beijing as participants. Participants were followed up for six months to collect data on general information, olfactory function testing, and cognitive function. According to whether there were changes in clinical cognitive function, older adults were divided into a cognitive function decline group and a cognitive function non-decline group. Binary Logistic regression was used to analyze the independent influencing factors of cognitive decline in older adults with MCI, and the receiver operating characteristic (ROC) curve was used to evaluate the predictive effect of olfactory function on cognitive decline.Results:Among 385 older adults with MCI, 113 (29.4%) experienced cognitive decline. Binary Logistic regression analysis showed that education level, passive cognition activity, social activity, and olfactory dysfunction were independent influencing factors for cognitive decline in older adults with MCI ( P<0.05). The area under the ROC curve was 0.819 [95% CI (0.773, 0.865), P<0.01], with an optimal cutoff value of 9.5 points, a sensitivity of 81.3% and specificity of 31.0%. Conclusions:The olfactory function has good predictive value for cognitive decline in older adults with MCI, and can be used for early screening of MCI high-risk individuals with rapid cognitive decline.
6.Scoping review on the application of gamification design in exercise interventions for elderly patients with cognitive impairment
Lanying XIE ; Huixiu HU ; Yajie ZHAO ; Jie GAO ; Huanhuan LUO ; Yuqing HAO ; Chao SUN
Chinese Journal of Modern Nursing 2024;30(32):4366-4372
Objective:To conduct a scoping review on gamified exercise interventions for elderly patients with cognitive impairment to provide insights for the application of gamification design in exercise programs for this population.Methods:Guided by the scoping review framework proposed by Arksey and O'Malley, a systematic search was conducted in databases including China National Knowledge Infrastructure, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, CINAHL, Web of Science, Scopus, ProQuest, and Wiley Online Library. The search covered the period from the establishment of the databases to June 12, 2024. An integrative analysis was performed on the included literature.Results:A total of 12 studies were included. The most commonly used gamification elements were achievement- and progress-oriented features, while the most frequently applied behavior change theories were behavior change techniques and social cognitive theory.Conclusions:Gamification-based exercise interventions can improve adherence to exercise programs in elderly patients with cognitive impairment, promote physical activity, and enhance cognitive function. Future research should focus on combining various theories with different gamification elements to encourage proactive exercise behavior in elderly individuals with cognitive impairment.
7.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.
8.Relationship between olfactory dysfunction and mild cognitive impairment among elderly people in community
Linzhi ZHANG ; Chao SUN ; Huixiu HU ; Yajie ZHAO ; Huanhuan LUO ; Jie GAO
Chinese Journal of Modern Nursing 2024;30(13):1757-1763
Objective:To explore the relationship between olfactory dysfunction and mild cognitive impairment (MCI) among elderly people in the community so as to provide a reference for screening and risk factor management of the MCI population.Methods:From March to June 2023, elderly individuals from Donghuashi and Fangzhuang communities in Beijing were selected as the study subjects by convenience sampling. Study subjects were surveyed using the General Information Questionnaire, Mini-Mental State Examination, Montreal Cognitive Assessment, Barthel Index, Sniffin' Sticks Test, 7-item Generalized Anxiety Disorder Scale, and 15-item Geriatric Depression Scale. Binary logistic regression was used to analyze the factors that influence MCI among elderly people in the community.Results:A total of 252 questionnaires were distributed and 243 valid questionnaires were collected, with an effective response rate of 96.4% (243/252). Among 243 elderly people in the community, 75 experienced MCI, with an incidence of 30.9% (75/243). Binary Logistic regression analysis showed that the probability of MCI in elderly people with olfactory dysfunctions was 1.979 times that in elderly people without olfactory dysfunctions and age, previous occupational type and frequency of mental activity were the influencing factors for the occurrence of MCI ( P<0.05) . Conclusions:The incidence of MCI is high among elderly people in the community, especially those with olfactory dysfunctions. Nursing staff should pay attention to the role of olfactory dysfunction in cognitive function screening and risk factor management.
9.Impact of pain on fatigue symptoms in elderly malignant tumor patients: parallel mediating effects of sleep disorders and depression
Jie GAO ; Huixiu HU ; Chao SUN ; Yajie ZHAO ; Pei WANG
Chinese Journal of Modern Nursing 2024;30(25):3423-3430
Objective:To construct a parallel mediation model from the perspective of symptom clusters to verify the mediating effect of sleep disorders and depression in the relationship between pain and fatigue in elderly malignant tumor patients, and explore the pathways and relationships of the internal symptoms of fatigue associated symptom clusters.Methods:From January to April 2022, convenience sampling was used to select 312 elderly patients with malignant tumors from Beijing Hospital as respondents. General Information Questionnaire, Numerical Rating Scale, Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, and Cancer Fatigue Scale were used for measurement. Spearman correlation was used to explore the correlation between pain, fatigue, depression, and sleep disorders, AMOS 24.0 was used to construct a parallel mediation model, and Bootstrap method was used to test the mediating effect.Results:A total of 312 questionnaires were distributed, and 305 valid questionnaires were collected, with an effective response rate of 97.76%. Pain of elderly patients with malignant tumors was positively correlated with fatigue ( r=0.436, P<0.01), sleep disorders ( r=0.316, P<0.01), and depression ( r=0.315, P<0.01), sleep disorders were positively correlated with fatigue ( r=0.491, P<0.01), and depression and fatigue were positively correlated ( r=0.587, P<0.01). The mediation model included two pathways: sleep disorders and depression partially mediated the relationship between pain and fatigue, accounting for 40.63% (0.221) and 14.89% (0.081) of the total effect (0.544), respectively. The total mediating effect was 55.51%, which was higher than the direct effect of 44.49%. Conclusions:There is a parallel mediating effect of pain-sleep disorder-depression-fatigue within the fatigue associated symptom cluster (pain, sleep disorders, depression, fatigue) in elderly malignant tumor patients. Medical and nursing staff can alleviate fatigue symptoms by improving the patient's pain condition and reducing their sleep disorders and depression symptoms.
10.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.

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