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.Correlation Analysis of Left Heart Volume and Atrial Fibrillation in Patients With Non-obstructive Hypertrophic Cardiomyopathy
Pan YANG ; Minghu XIAO ; Yajie TANG ; Qing WEI ; Xin QUAN ; Weichun WU ; Lei SONG ; Zhenhui ZHU
Chinese Circulation Journal 2025;40(3):240-245
Objectives:To analyze the risk factors of atrial fibrillation in patients with non-obstructive hypertrophic cardiomyopathy(NOHCM)and explore the relationship between left ventricular/atrial volume and atrial fibrillation.Methods:Consecutive NOHCM patients admitted at Fuwai Hospital from January 2023 to January 2024 with complete clinical data,satisfactory echocardiography imaging data were included in this analysis,patients were divided into atrial fibrillation group(n=28)and non-atrial fibrillation group(n=57).Left-sided volumetric and functional parameters were measured by one-beat real-time full-volume three-dimensional echocardiography,including left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),left atrial volume(LAV).The left ventricular end-diastolic volume(LVEDVi)index,left ventricular end-systolic volume index(LVESVi)and left atrial volume index(LAVi)were calculated.Other echocardiographic parameters including interventricular septum(IVSmax)thickness,left ventricular posterior wall thickness(LVPW),and left atrial diameter(LAD)were routinely measured.Mitral valve forward flow spectrum,tissue Doppler,tricuspid regurgitation velocity,and left atrial size were used to evaluate the left ventricular diastolic function of patients,and diastolic dysfunction was classified into grade I,II,and III.Multivariate logistic regression was used to analyze the influencing factors of atrial fibrillation in patients with non-obstructive hypertrophic cardiomyopathy Results:Compared with the non-atrial fibrillation group,LVEDV([143.8±26.7]ml vs.[117.1±21.9]ml)and LVEDVi([79.4±11.9]ml/m2 vs.[64.2±10.6]ml/m2)were smaller in atrial fibrillation group(both P<0.001).Compared with the non-atrial fibrillation group,LAD([40.2±4.7]mm vs.[48.6±4.8]mm)and LAVi([37.3±8.9]ml/m2 vs.[64.4±17.1]ml/m2)were lager in atrial fibrillation group(both P<0.001).Compared with the non-atrial fibrillation group,the proportion of NYHA functional classification≥Ⅲ was higher(15.8%vs.50.0%,P<0.001),LVEF was lower([61.5±5.5]%vs.[57.6±5.0]%,P=0.002),and proportion of severe diastolic dysfunction was higher in atrial fibrillation group(P<0.001).Logistic regression analysis showed that the factors associated with atrial fibrillation in NOHCM patients were LVEDVi(OR=0.744,95%CI:0.575-0.962,P=0.024)and LAVi(OR=1.602,95%CI:1.032-2.486,P=0.036).Conclusions:LVEDVi and LAVi are related factors for atrial fibrillation in patients with non-obstructive hypertrophic cardiomyopathy.LVEDVi is negatively,while LAVi is positively associated with the occurrence of atrial fibrillation in NOHCM patients.
3.Effects of edema metabolic and hematoma dynamics changes on motor and cognitive recovery in intracerebral hemorrhage patients based on MR spectroscopy imaging
Yajie CHEN ; Rongrong ZHANG ; Feng CHEN ; Xiang CHEN ; Yang LI ; Yuhao XU ; Yan ZHU ; Ranchao WANG
Journal of Practical Radiology 2025;41(5):721-725
Objective To investigate the predictive value of edema metabolic and hematoma dynamics changes on motor and cog-nitive recovery outcomes in patients with intracerebral hemorrhage(ICH).Methods The CT data of ICH patients were collected to evaluate hematoma volume changes from admission to day 3.On day 3,multivoxel magnetic resonance spectroscopy(MRS)was per-formed with region of interest located in the edema region and contralateral normal tissue.Motor and cognitive function recovery was assessed using the simplified F-M scale and the Montreal cognitive assessment(MoCA)on day 3 and at the 3-month follow-up,respec-tively.Overall clinical outcomes were assessed using the Glasgow outcome scale(GOS),and all patients were divided into good and poor outcome groups.Clinical data and metabolic differences in the edema region between the two groups were compared,respec-tively.Logistic regression analysis and receiver operating characteristic(ROC)curves were used to identify and evaluate independent prognostic factors.Subgroup analysis were performed via stratification of hematoma location.Results The logistic regression analy-sis indicated that intraventricular extension,hematoma changes,and the ratio of N-acetyl aspartate(NAA)around the hematoma to contralateral normal brain parenchyma NAA(rNAA)were inde-pendent prognostic factors for poor outcomes(P<0.05).The area under the curve(AUC)for each factor and the combined model were 0.69,0.73,0.79,and 0.82,respectively.In patients with ICH in the basal ganglia region,△F-M was negatively correlated with hematoma changes and positively correlated with rNAA value(P<0.001).In patients with ICH in the thalamic and lobar regions,△MoCA was not significantly correlated with hematoma changes(P>0.05),but was positively correlated with rNAA value(P<0.001).Conclusion The rNAA holds predictive value for motor and cognitive recovery outcomes following standard treatment.
4.Value of spectral CT multi-parameter imaging in preoperative prediction of lymphovascular invasion in invasive lung adenocarcinoma
Jinping MA ; Xiaoxu GUO ; Limin LEI ; Xiaofei YANG ; Yuhan ZHOU ; Yajie WANG ; Lina TAO ; Songwei YUE
Chinese Journal of Radiology 2025;59(9):997-1002
Objective:To investigate the value of quantitative parameters of dual-layer detector spectral CT (DLCT) in preoperative prediction of lymphovascular invasion (LVI) in invasive lung adenocarcinoma.Methods:This study employed a cross-sectional design. The data of 91 patients with primary lung adenocarcinoma confirmed by postoperative pathology who underwent DLCT enhanced scanning in the First Affiliated Hospital of Zhengzhou University from March 2022 to July 2024 were retrospectively collected. The patients were divided into LVI positive group and LVI negative group according to the postoperative pathology. Gender, age, smoking status, and lesion location were recorded,the clinical T-stage and N-stage were evaluated. Spectral base data images were generated based on the spectral reconstruction algorithm. Conventional CT features such as the size and density of the lesions were analyzed. The DLCT quantitative parameters such as 40 keV single-energy CT value (CT 40 keV), iodine density (ID), standardized iodine density (NID), and effective atomic number (Z eff) were measured. The differences of parameters between the two groups were compared using t-test, Mann-Whitney U test, or χ2 test. Multivariate logistic regression analysis was used to identify independent factors for predicting invasive lung adenocarcinoma LVI. The predictive performance of individual parameters and their combinations for LVI in invasive lung adenocarcinoma was evaluated using receiver operating characteristic curve analysis and area under the curve (AUC) measurements. Results:There were significant differences in age, T stage, N stage, maximum diameter, focal density, and arteriovenous stage NID and Z eff between the LVI positive group and the LVI negative group ( P<0.05). Multiple logistic regression analysis showed that age ( OR=0.890, 95% CI 0.821-0.966), N stage( OR=12.721, 95% CI 2.676-60.473) and venous stage Z eff( OR=0.012,95% CI 0-0.668) were independent factors for predicting invasive lung adenocarcinoma LVI ( P<0.05). The combination of age, N stage, and venous-phase Z eff values demonstrated the highest predictive efficacy for LVI in invasive lung adenocarcinoma, with an AUC of 0.916. Conclusions:The quantitative parameters of DLCT are helpful for preoperative prediction of LVI status of invasive lung adenocarcinoma. The Z eff in the venous stage is an independent predictor, the combination of multiple parameters can further improve the diagnostic efficiency.
5.Analysis of factors correlating with the initial seizure threshold in modified electroconvulsive therapy for patients with mental disorders
Yingyin LI ; Peng YANG ; Meijie WANG ; Yajie SHI ; Yanfei LI ; Kun LI ; Xiaoming ZHANG
Sichuan Mental Health 2025;38(4):302-307
BackgroundModified electroconvulsive therapy (MECT) is a common front-line strategy widely used in psychiatric practice, and the optimal first stimulus dosage in MECT is usually estimated clinically based on the factors influencing the patient's initial seizure threshold (IST). However, previous studies on the influencing factors of IST have mostly suffered from limitations such as small sample sizes and single-dimensional research perspectives. ObjectiveTo explore the factors influencing IST in MECT for patients with mental disorders, so as to provide references for stimulus dosing strategies in MECT for the patients. MethodsA retrospective study was used to include 1 446 inpatients fulfilling the diagnostic criteria for any specific mental disorder listed in the ICD-10 and receiving MECT at Shandong Daizhuang Hospital from January 1, 2021 to August 1, 2023. Their general and clinical data were collected, including IST, psychiatric diagnostic categories, gender, ethnicity, age, body weight, body mass index (BMI), course of disease, family history of psychiatric disorders, first episode status, use of antiepileptic drugs the day before treatment, use of benzodiazepines the day before treatment, and previous MECT treatment history. Pearson correlation analysis was utilized to test the correlation of IST with age, height, body weight, BMI, and course of disease, and stepwise multivariate linear regression analysis was performed to identify the factors affecting IST. ResultsIST yielded statistical difference among patients in terms of gender, first episode status, use of antiepileptic drugs the day before treatment, and use of benzodiazepines the day before treatment (t=2.256, -3.059, -2.136, -3.006, P<0.05 or 0.01). IST in patients of different ages and psychiatric diagnostic categories also demonstrated statistical difference (F=913.120, 6.212, P<0.01). Within young population, IST varied significantly based on the psychiatric diagnostic categories (F=2.986, P<0.05). Correlation analysis indicated that IST was positively correlated with age, body weight, BMI and course of disease (r=0.886, 0.055, 0.184, 0.456, P<0.05 or 0.01), and negatively correlated with height (r=-0.183, P<0.01). Stepwise multivariate linear regression analysis revealed that age, gender, and body weight were influencing factors of IST (β=0.888, -0.049, -0.035, P<0.01). ConclusionsAge, gender and body weight may be factors influencing IST in MECT for patients with mental disorders. [Funded by Key R&D Plan Projects of Jining City in 2024 (number, 2024YXNS202)]
6.A Survey on the Prevalence of Hyperuricemia among Ethnic Minorities in Gongshan County,Yunnan Province
Yajie SHEN ; Yali YANG ; Zhiqing YU ; Cheng QIAO
Journal of Kunming Medical University 2025;46(3):39-43
Objective To investigate the prevalence of hyperuricemia among ethnic groups in Gongshan county,Yunnan province through a cross-sectional study.Methods A total of 229 residents aged ≥ 18 years from Dulong,Nu,Tibetan,Bai and Lisu ethnic groups were randomly selected in Gongshan County of Yunnan Province for questionnaire survey,physical examinations and laboratory tests.SPSS 22.0 was used for t test,Chi-square test,correlation analysis,and multivariate logistic regression analysis.Results A total of 107 cases of hyperuricemia were identified,with a detection rate of 46.7%,among which the prevalence was 43.9%in males,52.63%in female,48%in the Dulong,51%in the Lisu,47%in the Nu,37.5%in the Bai,52%in the Tibetan and 50%in the Han.There were no statistically significant differences in prevalence among all nationalities(P>0.05).The proportion of individuals with a history of diabetes,as well as levels of urea nitrogen and serum creatinine,were significantly higher in the hyperuricemia group compared to the non-hyperuricemia group(P<0.05).Correlation analysis showed a positive correlation between hyperuricemia and diabetes,urea nitrogen and serum creatinine.(P<0.05).Multivariate regression analysis showed that diabetes and elevated serum creatinine were independent risk factors for the onset of hyperuricemia(P<0.05).Conclusion The detection rate of hyperuricemia is relatively high in Gongshan County,Yunnan Province,and there is no significant differences in prevalence among ethnic groups.Diabetes and elevated serum creatinine are associated with hyperuricemia,which increase the risk of developing hyperuricemia.
7.Mechanism of Huangqi Gegen Decoction in Treatment of Type 2 Diabetes Mellitus via Intestinal Mucosal Barrier
Lili PENG ; Miao HAO ; Zhijun YANG ; Yajie LIU ; Hongxia YUAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):1-9
ObjectiveTo investigate the mechanism of Huangqi Gegentang (HGT) in the treatment of type 2 diabetes mellitus (T2DM) through the application of proteomic techniques. MethodsThe rat model of T2DM was established by streptozotocin combined with a high-fat, high-sugar diet. Thirty-two male SD rats were randomized into four groups: blank, model, HGT (8.10 g·kg-1·d-1), and positive control (metformin hydrochloride, 76.5 mg·kg-1·d-1). After 6 weeks of drug intervention, the fasting blood glucose level was measured, and an oral glucose tolerance test (OGTT) was performed. The area under the curve (AUC) was calculated. Enzyme-linked immunosorbent assay was performed to assess the level of glycated hemoglobin (GHbA1c) in the serum. The limulus amebocyte lysate assay was employed to measure the serum level of lipopolysaccharide (LPS). Pathological changes in the colon were observed by hematoxylin-eosin staining. The mRNA levels of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the colon tissue were quantified via Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Additionally, the protein and mRNA levels of zonula occludens-1 (ZO-1), Occludin, and Claudin-1 in the colon tissue were assessed by Western blot and Real-time PCR, respectively. Label-free quantitative proteomics was employed to identify the differentially expressed proteins between the colon tissue samples from the blank, model, and HGT groups. Key proteins identified were subsequently validated by Western blot and Real-time PCR. Finally, bioinformatics analysis was conducted on the differentially expressed proteins. ResultsCompared with the blank group, the model group exhibited increased fasting blood glucose, AUC, and GHbA1c levels (P<0.01), damaged colonic mucosal epithelial structure and inflammatory cell infiltration, up-regulated mRNA levels of TNF-α, IL-6, and IL-1β in the colon and an increase in serum LPS content (P<0.05, P<0.01), and down-regulated protein and mRNA levels of ZO-1, Occludin, and Claudin-1 in the colon (P<0.01). Compared with the model group, the HGT group showed reductions in fasting blood glucose, AUC, and GHbA1c (P<0.01), alleviated damage to the colonic mucosal epithelium, down-regulated mRNA levels of TNF-α, IL-6, and IL-1β in the colon, a reduction in serum LPS content (P<0.05, P<0.01), and up-regulated protein and mRNA levels of ZO-1, Occludin, and Claudin-1 in the colon (P<0.05, P<0.01). Proteomics analysis identified 70 differentially expressed proteins that exhibited a downward trend in the model group relative to the blank group and an upward trend in the HGT group relative to the model group. These findings were corroborated by Western blot and Real-time PCR, which confirmed that the protein and mRNA levels of mucin 2 (Muc2) and transforming growth factor (TGF)-beta receptor 1 (Tgfbr1) in the colon tissue were consistent with the proteomic data. Bioinformatics analysis showed that these 70 differentially expressed proteins identified were significantly enriched in multiple signaling pathways, among which the TGF-β and advanced glycation endproduct (AGE)/receptor for advanced glycation endproduct (RAGE) signaling pathways were closely associated with damage to the intestinal mucosal barrier. This suggests that HGT may ameliorate intestinal mucosal barrier damage by regulating these pathways. ConclusionHGT potentially exerts anti-T2DM effects by influencing AGE/RAGE and TGF-β signaling pathways, thereby contributing to the restoration of the intestinal mucosal barrier.
8.Feasible study on implementing daily quality assurance for linear accelerator with electronic portal imaging device
Daming LI ; Yan WU ; Jinsen XIE ; Zhaoming PENG ; Pengfei YANG ; Zhe ZHANG ; Yajie LIU
Chinese Journal of Medical Physics 2025;42(1):14-19
Objective To analyze the performances of electronic portal imaging device (EPID) in mechanical and dosimetry responses,and to investigate the feasibility of adopting EPID as a daily quality assurance (QA) equipment. Methods The EPID of Trilogy linear accelerator was tested for mechanical position repeatability and dose linear response. Then,a group of special fields were edited manually for simulations of field translation and symmetry deviations,and the sensitivities of EPID and MyQA Daily to field translation and symmetry deviations were evaluated,and moreover,the linear correlation between the set value and the measured value was analyzed. Finally,daily QA was conducted with EPID and MyQA Daily for 30 consecutive days,and the measurement results and time consumption were analyzed. Results The maximum deviation of EPID position repeatability was 0.4 mm,and the dose response was linearly correlated (R2>0.999). The symmetry deviation test results showed that both of EPID and MyQA Daily were capable to effectively detect the 0.2% offset in symmetry,and a linear correlation was demonstrated between the set value and the measured results (R2>0.995). In translation test,the linear correlation of EPID was more explicit than that of MyQA Daily (R2=0.992 vs R2=0.976). In daily QA,all the measured results of EPID and MyQA Daily were within the clinic acceptance tolerance. Moreover,the mean value of Y-directional symmetry and flatness measured by EPID was approximately 1.00% larger than MyQA Daily. The average time required by EPID was 50 s less than MyQA Daily[(129.97±4.16) s vs (184.53±4.23) s]. Conclusion EPID can be served as a reliable and efficient daily QA equipment for linear accelerator. However,it is not capable to be used as a criterion for evaluating linear accelerator performance.
9.Status of career planning and its influencing factors among medical students in Wuhan, China: a study based on the knowledge-attitude-practice theory
Suwei LIU ; Yajie YU ; Hao LIU ; Zhennan HAN ; Haiyun YU ; Shengli YANG
Chinese Journal of Medical Education Research 2025;24(1):55-61
Objective:To investigate the current status of knowledge, attitude, and practice in career planning among medical students and its influencing factors, and to facilitate the education of medical career planning.Methods:The convenience sampling method was used to distribute a self-made questionnaire, and related data were gathered from 295 medical students in Wuhan, China. SPSS 26.0 was used to perform analyses of related categorical variables, including descriptive statistics, univariate tests, rank-sum tests, and the binary logistic regression analysis.Results:The results showed that the medical students with good performance of career planning knowledge, attitude, and practice accounted for 68.48%, 87.12%, and 54.92%, respectively. Major, grade, professional satisfaction, and professional learning objectives were influencing factors for career planning knowledge among the medical students ( P<0.05); the intention for laboratory participation, the basis for major selection, and professional learning objectives were influencing factors for career planning attitude ( P<0.05); grade, internship experience, and professional learning objectives were influencing factors for career planning practice ( P<0.05). Conclusions:Related measures should be adopted to strengthen career planning education for medical talents, such as perfecting the whole-process and multi-agent career planning guidance system, stimulating the enthusiasm of students, and clarifying professional learning objectives.
10.Correlation Analysis of Left Heart Volume and Atrial Fibrillation in Patients With Non-obstructive Hypertrophic Cardiomyopathy
Pan YANG ; Minghu XIAO ; Yajie TANG ; Qing WEI ; Xin QUAN ; Weichun WU ; Lei SONG ; Zhenhui ZHU
Chinese Circulation Journal 2025;40(3):240-245
Objectives:To analyze the risk factors of atrial fibrillation in patients with non-obstructive hypertrophic cardiomyopathy(NOHCM)and explore the relationship between left ventricular/atrial volume and atrial fibrillation.Methods:Consecutive NOHCM patients admitted at Fuwai Hospital from January 2023 to January 2024 with complete clinical data,satisfactory echocardiography imaging data were included in this analysis,patients were divided into atrial fibrillation group(n=28)and non-atrial fibrillation group(n=57).Left-sided volumetric and functional parameters were measured by one-beat real-time full-volume three-dimensional echocardiography,including left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),left atrial volume(LAV).The left ventricular end-diastolic volume(LVEDVi)index,left ventricular end-systolic volume index(LVESVi)and left atrial volume index(LAVi)were calculated.Other echocardiographic parameters including interventricular septum(IVSmax)thickness,left ventricular posterior wall thickness(LVPW),and left atrial diameter(LAD)were routinely measured.Mitral valve forward flow spectrum,tissue Doppler,tricuspid regurgitation velocity,and left atrial size were used to evaluate the left ventricular diastolic function of patients,and diastolic dysfunction was classified into grade I,II,and III.Multivariate logistic regression was used to analyze the influencing factors of atrial fibrillation in patients with non-obstructive hypertrophic cardiomyopathy Results:Compared with the non-atrial fibrillation group,LVEDV([143.8±26.7]ml vs.[117.1±21.9]ml)and LVEDVi([79.4±11.9]ml/m2 vs.[64.2±10.6]ml/m2)were smaller in atrial fibrillation group(both P<0.001).Compared with the non-atrial fibrillation group,LAD([40.2±4.7]mm vs.[48.6±4.8]mm)and LAVi([37.3±8.9]ml/m2 vs.[64.4±17.1]ml/m2)were lager in atrial fibrillation group(both P<0.001).Compared with the non-atrial fibrillation group,the proportion of NYHA functional classification≥Ⅲ was higher(15.8%vs.50.0%,P<0.001),LVEF was lower([61.5±5.5]%vs.[57.6±5.0]%,P=0.002),and proportion of severe diastolic dysfunction was higher in atrial fibrillation group(P<0.001).Logistic regression analysis showed that the factors associated with atrial fibrillation in NOHCM patients were LVEDVi(OR=0.744,95%CI:0.575-0.962,P=0.024)and LAVi(OR=1.602,95%CI:1.032-2.486,P=0.036).Conclusions:LVEDVi and LAVi are related factors for atrial fibrillation in patients with non-obstructive hypertrophic cardiomyopathy.LVEDVi is negatively,while LAVi is positively associated with the occurrence of atrial fibrillation in NOHCM patients.

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