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.Research progress on influencing factors of immunotherapy-related adverse events in patients with malignant tumors
Yajie SI ; Renshan CUI ; Yue XIN ; Wenwen HU
Journal of Shenyang Medical College 2024;26(5):524-528
Immune checkpoint inhibitors(ICIs)are an emerging tumor treatment approach following traditional surgery,chemoradiotherapy and targeted therapy.They have proven to be effective in a variety of cancers.However,they may induce immune-related adverse events(irAEs)during treatment,which may affect patients'quality of life and lead to treatment interruption or cessation.The key to preventing irAEs is early evaluation and identification of medical staff.Therefore,this article reviews the clinical manifestations and influencing factors of irAEs to help the early identification of high-risk groups and provide reference for clinical nursing work.
3.Effects of Jiaohong Pills and Its Prescription on Scopolamine-induced Alzheimer's Disease Mice
Lijinchan DONG ; Weiyan CAI ; Li FENG ; Qing YANG ; Mengting LI ; Yanli WANG ; Hong ZHANG ; Qi LI ; Xiaogang WENG ; Yajie WANG ; Xiaoxin ZHU ; Xiaoru HU ; Ying CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):37-45
ObjectiveTo investigate the effects of Jiaohong pills (JHP) and its prescription, Pericarpium Zanthoxyli (PZ) and Rehmanniae Radix (RR) cognitive dysfunction in scopolamine-induced Alzheimer's disease (AD) mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ, RG and JHP, respectively. The effects of JHP and its formulations were investigated by open field test, water maze test, object recognition test, avoidance test, cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry (UPLC Q-Exactive Orbitrap MS). ResultThe behavioral data showed that, compared with the model group, the discrimination indexes of the high dose of JHP, PZ and RR groups was significantly increased (P<0.05). The staging rate of Morris water maze test in the PZ, RR, high and low dose groups of JHP was significantly increased (P<0.05, P<0.01), the crossing numbers in the PZ, JHP high and low dose groups were significantly increased (P<0.05, P<0.01); the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups (P<0.01), and the error latencies were significantly increased in the JHP and its prescription drug groups (P<0.01). Compared with the model group, the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased (P<0.05, P<0.01), and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased (P<0.05), and the level of acetylcholine was significantly increased (P<0.01). At the same time, the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly (P<0.05, P<0.01). The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group, which were involved in neurotransmitter metabolism, energy metabolism, oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction, regulate cholinergic system, and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter, energy, amino acid metabolism, and improvement of oxidative stress.
4.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.
5.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.
6.Inhibitory effects of magnesium citrate on oxidative stress in chronic renal failure
Zhihui YAO ; Weidong MA ; Tuo HAN ; Yajie FAN ; Chunyan ZHANG ; Yan ZHANG ; Yanchao HU ; Congxia WANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(5):712-717
Objective To investigate the inhibitory effects of magnesium citrate(MgCit)on oxidative stress in chronic renal failure(CRF).Methods SD rats were divided into CRF model group,MgCit groups(375 and 750 mg/kg),normal control group,and MgCit control group(750 mg/kg).The morphology of mitochondria in thoracic artery vascular smooth muscle cells(VSMCs)was observed by transmission electron microscopy.The content of superoxide dismutase(SOD)and malonaldehyde(MDA)in rat aorta and plasma was detected by the kit.The VSMCs were divided into normal control group,CRF model group,and MgCit groups(1.5 and 3 mmol/L).The levels of superoxide anion(DHE)and apoptosis were quantitatively detected by flow cytometry.Results Compared with the control groups,the mitochondria were swollen and the cristae fractured or disappeared in the model group;MgCit intervention could reduce mitochondrial swelling,but not cristae fracture.In the model group,SOD level in aorta and plasma decreased(P<0.05)while MDA level increased(P<0.05).MgCit intervention could increase SOD in aorta and plasma,but decrease MDA level(P<0.05).In the CRF environment,the DHE content of VSMCs and apoptosis in CRF model group increased(P<0.05).MgCit intervention could decrease DHE content and inhibit apoptosis(P<0.05).Conclusion MgCit inhibits oxidative stress levels in vivo and in vitro in CRF.
7.Effect of modified Zhuyu Decoction combined with oxytocin on uterine involvment and residual of placenta in postpartum patients
Wenjing LIN ; Yuting HU ; Meimei WANG ; Jun WANG ; Yajie YAN
Journal of Chinese Physician 2024;26(11):1642-1646
Objective:To investigate the effect of Jiawei Zhuyu Decoction combined with oxytocin on uterine involvement and residual of placenta in postpartum patients.Methods:A total of 91 patients with postpartum placenta residue admitted to Baoji Central Hospital from January 2023 to January 2024 were selected as the study objects. According to random number table method, the patients were divided into observation group (45 cases) and control group (46 cases). The control group was treated with oxytocin, and the observation group was treated with Jiawei Zhuyu decoction. Treatment effect, Traditional Chinese Medicine (TCM) symptom score, Visual Analogue Scale (VAS) score, SF-36 score, uterine reversion, uterine residual area, levels of beta human chorionic gonadotropin (β-HCG), progesterone (P), estradiol (E 2), duration of vaginal bleeding, length of hospital stay and adverse reactions were compared between the two groups. Results:The total effective rate of the observation group was higher than that of the control group [95.6%(43/45) vs 78.3%(36/46), χ 2=5.943, P=0.015]. After treatment, TCM syndrome scores, VAS scores and SF-36 scores of 2 groups were significantly improved (all P<0.05), and TCM syndrome scores and VAS scores of observation group were lower than those of control group, and SF-36 scores were higher than those of control group (all P<0.05). After treatment, the sum of three diameters of uterus, endometrial thickness and area of uterine residue in both groups decreased (all P<0.05), and the sum of three diameters of uterus, endometrial thickness, rate of uterine decline and area of uterine residue in the observation group were smaller than those in the control group (all P<0.05). After treatment, the levels of β-HCG, P, E 2 in 2 groups were improved compared with before (all P<0.05), and the levels of β-HCG and P in observation group were lower than those in the control group, and E 2 levels were higher than those in the control group (all P<0.05). The duration of vaginal bleeding and hospitalization in the observation group were shorter than those in the control group (all P<0.05). The incidence of adverse reactions in the observation group was lower than that in the control group [6.67%(3/45) vs 21.7%(10/46), χ 2=4.220, P=0.040]. Conclusions:Jiawei Zhuyu Decoction combined with oxytocin has a good effect on postpartum placenta residue, can effectively reduce the intrauterine placenta residue, promote uterine involution, and accelerate the recovery of patients.
8.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.
9.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.
10.Three-dimensional analysis of force distribution on maxillary dentition while distalization of first and second molars simultaneously with clear aligners
Xuhui HE ; Zexuan YANG ; Xiayu ZHANG ; Yajie FAN ; Yirong HU ; Zexu GU
Chinese Journal of Stomatology 2024;59(10):1037-1043
Objective:To explore the force distribution on the maxillary dentition when the first and second molars distalized simultaneously with different step sizes using clear aligners in vitro in order to provide a theoretical basis for the rational design of molar distalization. Methods:Clear aligners were designed to simultaneously distalize the maxillary first and second molars bilaterally, with rectangular attachments placed on the buccal surfaces of the first and second premolars, as well as the second molars. Based on different step sizes, the aligners were divided into three groups: Group A (0.15 mm per step), Group B (0.20 mm per step), and Group C (0.25 mm per step). Ten aligners were fabricated for each group using 0.76 mm thick polyethylene terephthalate glycol (PET-G) sheets. A three-dimensional force measurement system was used to measure the forces exerted on each tooth by the aligners, the first and second molars served as the target teeth and the remaining teeth as anchorage teeth. The three-dimensional force data were compared among the three groups.Results:In the mesiodistal direction, the forces on the central and lateral incisors were relatively small among all three groups, with no statistically significant differences ( P>0.05). However, significant differences were observed in the forces on the canines, first premolars, second premolars, first molars, and second molars ( P<0.05). The distal forces on the second molars in Groups B and C were (6.13±1.45) N and (6.83±1.58) N, respectively, significantly higher than that in Group A [(3.51±1.01) N] ( P<0.05). The distal force on the first molars in Group C [(6.62±0.89) N] was significantly higher than that in Groups A and B ( P<0.05). The mesial reactive forces on the first and second premolars in Groups B and C were significantly higher than those in Group A ( P<0.05). The mesial reactive force on the canines in Group C [(-2.98±1.33) N] was significantly higher than that in Group A [(-1.69±0.68) N] ( P<0.05), while there were no significant differences between Groups B and C in the forces on the canines, first premolars, and second premolars ( P>0.05). In the buccolingual direction, there were no statistically significant differences in the forces on the central and lateral incisors among three groups ( P>0.05), but significant differences were observed in the forces on the canines, second premolars, and second molars ( P<0.05). The buccolingual forces on the canines, second premolars, and second molars in Group B were (-0.56±0.54), (-2.07±0.95), (1.13±0.55) N, respectively, significantly higher than those in Group A ( P<0.05), but there were no significant differences compared to Group C ( P>0.05). Compared to the mesiodistal and buccolingual forces, the vertical forces on the target and anchorage teeth were relatively small in all three groups. Conclusions:When using 0.76 mm thick PET-G sheets to fabricate clear aligners for simultaneous molar distalization, a step size of 0.20 mm per step is recommended. To prevent buccal tipping of the molars during distalization, it is advisable to design lingual displacement for the molars and buccal displacement for the adjacent anchorage teeth to counteract the unfavorable forces, with attachments placed on the primary anchorage teeth.

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