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.

The repeated administration of morphine frequently gives rise to tolerance,manifested by a reduction in analgesic efficacy and an elevation in adverse effects.These consequences significantly impinge upon its clinical utility.Synaptic functional plasticity governs long-term alterations in synaptic transmission efficiency through calcium signaling pathways,protein kinase cascade reactions,and glia-neuron interactions,thereby facili-tating the development of morphine tolerance.Structural plasticity encompasses the dynamic remodeling of dendritic spine density and morphology,the establishment or elimination of synaptic connections,and the reconstitution of synaptic active zones.Morphine-induced synaptic plasticity within the central nervous system demonstrates region-specific alterations,which jointly drive the process of tolerance.This review comprehensively synthesizes the research advancements regarding the mechanisms of synaptic plasticity in morphine tolerance,with the aim of furnishing a theoretical foundation for the development of innovative analgesic medications and the optimization of clinical treatment strategies.

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.

The repeated administration of morphine frequently gives rise to tolerance,manifested by a reduction in analgesic efficacy and an elevation in adverse effects.These consequences significantly impinge upon its clinical utility.Synaptic functional plasticity governs long-term alterations in synaptic transmission efficiency through calcium signaling pathways,protein kinase cascade reactions,and glia-neuron interactions,thereby facili-tating the development of morphine tolerance.Structural plasticity encompasses the dynamic remodeling of dendritic spine density and morphology,the establishment or elimination of synaptic connections,and the reconstitution of synaptic active zones.Morphine-induced synaptic plasticity within the central nervous system demonstrates region-specific alterations,which jointly drive the process of tolerance.This review comprehensively synthesizes the research advancements regarding the mechanisms of synaptic plasticity in morphine tolerance,with the aim of furnishing a theoretical foundation for the development of innovative analgesic medications and the optimization of clinical treatment strategies.

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.

Objective To explore the influence of impulsivity on digital addiction tendencies in patients with Wilson disease(WD)and its related factors.Methods A total of 66 patients with WD were included in the study which were divided into neurological WD group(42 cases)and hepatic WD group(24 cases)according to clinical manifestations.Sixty-six WD patients were included as the study subjects,including 24 cases of hepatic WD and 42 cases of neurological WD.The Chinese version of the Barratt impulsiveness scale(BIS-11-C)was used to assess patients'impulsiveness.Mobile phone addiction index(MPAI)evaluates the degree of dependence on mobile phone use.Cranial MRI was used to examine the location and cumulative frequency of the diseased brain region.Results Among the 66 WD patients,45 cases(68.2% )had the tendency of digital addiction,including 35 cases(53.0% )in the neurological WD group and 10 cases(15.2% )in the hepatic WD group.There was a statistically significant difference in the proportion of the two types of WD patients(P=0.001).The scores of BIS-11-C and MPAI scales in neurological WD group were higher than those in hepatic WD group(P<0.05).The out-of-control score in the MPAI scale is positively correlated with the attention impulsivity score(r=0.499,P=0.001),motor impulsivity score(r=0.553,P=0.001),unplanned impulsivity score(r=0.535,P=0.001),and impulse control score(r=0.653,P=0.001)in the BIS-11-C scale.Linear regression analysis showed a correlation between attention impulsivity score and frontal lobe lesions(B=-1.634,P=0.018).There was a correlation between loss of control score and frontal lobe lesions(B=-3.609,P=0.023).The withdrawal score was associated with the thalamus lesions(B=-5.047,P=0.007)and frontal lobe lesions(B=-2.204,P=0.024).Avoidance score was associated with parietal lobe lesions(B=-1.867,P=0.032).The low efficacy score was associated with the putamen lesions(B=-1.789,P=0.016)and frontal lobe lesions(B=-1.592,P=0.044).Conclusion Neurological WD patients have higher tendency of digital addiction than hepatic WD patients and the tendency of digital addiction is related to impulsivity.The digital addiction tendency of WD patients may be related to impulse control disorders caused by lesions in multiple brain regions such as the putamen,thalamus,and frontal lobe.

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.

Objective:To investigate the hepatitis B surface antigen (HBsAg) clearance condition and its predictive factors after treatment with nucleos(t)ide analogues to pegylated interferon-α add-on therapy in patients with chronic hepatitis B.Methods:Patients with chronic hepatitis B who visited the First Affiliated Hospital of Zhengzhou University from 2018~2019 were prospectively enrolled. HBsAg≤ 1500 IU/mL, hepatitis B e antigen-negative, HBV DNA undetectable, received antiviral treatment with nucleos(t)ide analogues for at least one year, and pegylated interferon-α add-on therapy for 48 weeks were included. The primary endpoint of study was to determine the proportion of HBsAg clearance at 72 weeks. Concurrently, the predictive factors for HBsAg clearance were analyzed. Quantitative and qualitative data were analyzed using a t-test or non-parametric test and a Fisher's exact test.Results:A total of 38 cases were included in this study, of which 13 cases obtained HBsAg clearance at 48 weeks of therapy and another six cases obtained HBsAg clearance throughout the extended treatment period of 72 weeks, accounting for 50.00% of all enrolled patients. There was a significant difference in HBsAg dynamics between the HBsAg clearance group and the non-clearance group (P < 0.05). Univariate logistic regression analysis showed that patients' age, baseline, 12-and 24-week HBsAg levels, and early HBsAg reduction were predictive factors for HBsAg clearance at 72 weeks of treatment. Multivariate logistic regression analysis showed that age (OR = 1.311; P = 0.016; 95% confidence interval: 1.051~1.635) and HBsAg levels at 24 weeks of treatment (OR = 4.481; P = 0.004; 95% confidence interval: 1.634~12.290) were independent predictors for HBsAg clearance.Conclusion:Hepatitis B e antigen-negative, nucleos(t)ide analogue treated, HBsAg ≤ 1500 IU/mL, and HBV DNA undetectable, peg-IFNα add-on treatment for 48 weeks could promote HBsAg clearance in patients with chronic hepatitis B. Six of the sixteen cases (37.50%) who did not obtain HBsAg clearance at week 48 did so with the course of therapy extended to week 72. Hence, the optimal individualized treatment strategy should be customized according to the predictors rather than the fixed 48-week course. Age (≤ 38), baseline HBsAg level (≤2.86 log 10IU/ml), HBsAg level at 24 weeks (≤ 0.92 log 10IU/ml), and 12-week HBsAg decrease from baseline (≥ 0.67 log 10IU/ml) indicate that patients are highly likely to obtain HBsAg clearance at the 72 weeks of combination therapy, in which the combined indicator based on HBsAg level ≤0.92 log 10IU/ml at 24 weeks will identify 85.0% to 100.0% of patients with HBsAg clearance.

Objective    To investigate the clinical efficacy of preoperative location of pulmonary nodules guided by electromagnetic navigation bronchoscopy (ENB). Methods    Patients who received preoperative ENB localization and then underwent surgery from March 2021 to November 2022 in the Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine were collected. The clinical efficacy and safety of ENB localization and the related factors that may affect the success of ENB localization were analyzed. Results    Initially 200 patients were included, among whom 17 undergoing preoperative localization and biopsy were excluded and a total of 183 patients and 230 nodules were finally included. There were 62 males and 121 females with a mean age of 49.16±12.50 years. The success rate of navigation was 88.7%, and the success rate of ENB localization was 67.4%. The rate of complications related to ENB localization were 2.7%, and the median localization time was 10 (7, 15) min. Multi-variable analysis showed that factors related to successful localization included distance from localization site (OR=0.27, 95%CI 0.13-0.59, P=0.001), staining material (OR=0.40, 95%CI 0.17-0.95, P=0.038), and staining dose (OR=60.39, 95%CI 2.31-1 578.47, P=0.014). Conclusion     ENB-guided preoperative localization of pulmonary nodules is safe and effective, and the incidence of complications is low, which can be used to effectively assist the diagnosis and treatment of early lung cancer.

Objective:To explore the influencing factors of HIV-1 DNA and its clinical value.Methods:The relationship between HIV-1 DNA and CD4 + T cell count, CD4/CD8, HIV viral load and subtype was analyzed in 304 patients with HIV/AIDS in order to explore the factors affecting HIV-1 DNA and the value of clinical application. Results:There was no statistically significant difference in HIV-1 DNA levels between the different CD4 + T cell level groups (Z=1.194, P>0.05). HIV-1 DNA levels were higher in the CD4/CD8≤0.5 group than in the CD4/CD8>0.5 group (Z=-2.788, P<0.01). HIV-1 DNA levels were higher in the HIV viral load >100 copies/ml group than in the ≤100 copies/ml group (Z=-2.953, P<0.01). HIV-1 DNA levels were higher in those with CD4 + T cell counts ≤200 at diagnosis than in those with CD4 + T cell counts >200 at diagnosis (Z=-2.175, P<0.05). HIV-1 DNA levels were higher in patients with CD4/CD8 ≤0.2 at diagnosis than in those with CD4/CD8 between 0.2 and 0.5, but there was no significant difference between the two groups (Z=-0.893, P>0.05). HIV-1 DNA levels were higher in both groups than in the CD4/CD8≥0.5 group (Z=-2.568, Z=-1.960, P<0.05). Higher HIV-1 DNA levels were found in people with an HIV viral load >100, 000 copies/ml at diagnosis than in people with an HIV viral load ≤100, 000 copies/ml at diagnosis (Z=-3.520, P<0.001). The level of HIV-1 DNA was higher in the CRF01_AE group than in the non-CRF01_AE group, and the difference was statistically significant (Z=-2.848, P<0.01). CD4/CD8 seemed to be a protective factor for HIV-1 DNA>500 copies/ml. (OR=0.214(95%CI: 0.056~0.822, P<0.05) Conclusion:CD4 + T lymphocyte count, CD4/CD8, viral load and subtype are factors that influence HIV-1 DNA levels, while HIV-1 DNA may be informative for immune status assessment and disease progression determination.