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.

Objective:To investigate the epidemiological characteristics, disease spectrum, and laboratory characteristics of human immunodeficiency virus/cytomegalovirus (HIV/CMV) co-infection, to provide references for clinical diagnosis and treatment.Methods:A cross-sectional study was conducted. Clinical information of 544 HIV/acquired immune deficiency syndrome (AIDS) patients who underwent CMV-DNA tests in Beijing Ditan Hospital in 2023 was collected. Participants were categorized into CMV-infection group (126 cases) and non-CMV-infection group (418 cases). The prevalence of CMV infection was analyzed. Univariate and multivariate logistic regression analysis were performed to identify risk factors for CMV/AIDS co-infection. The disease spectrum, laboratory characteristics, serum CMV-DNA load changes, treatment prognosis and outcomes in the CMV-infected group were evaluated. SPSS 27.0 was used for statistical analysis including the χ 2 test, Mann-Whitney U test, and Kruskal-Wallis H test. Results:The CMV infection rate among HIV/AIDS patients was 23.16% (126/544). Multivariate analysis identified low CD4 +T-lymphocyte count [<50 cells/μl; OR=27.962, 95% confidence interval( CI) 11.957-65.389] and high HIV RNA load (>1×10 5 copies/ml; OR=2.057, 95% CI 1.237-3.420) as independent risk factors for CMV co-infection in HIV/AIDS patients. Among the 126 HIV/CMV co-infected patients, CMV viremia was the most common manifestation (38.10%, 48/126), followed by CMV pneumonia (33.33%, 42/126) and CMV retinitis (11.90%, 15/126), which were mainly observed in patients with CD4 +T-lymphocyte counts <50 cells/μl. Of the patients receiving anti-CMV therapy, 80.70% (46/57) exhibited reduced CMV-DNA loads compared with baseline. Totally 29.82% (17/57) of those patients initiating antiretroviral therapy alone achieved CMV-DNA reduction compared with baseline. Overall, 80.16% (101/126) of patients achieved favorable prognosis. Conclusion:CMV co-infection is high in HIV/AIDS patients. Disease spectrum of HIV/CMV co-infection are dominated by CMV viremia and CMV pneumonia. Timely anti-CMV therapy is pivotal for reducing CMV-DNA loads and improving prognosis.

Objective:To investigate the epidemiological characteristics, disease spectrum, and laboratory characteristics of human immunodeficiency virus/cytomegalovirus (HIV/CMV) co-infection, to provide references for clinical diagnosis and treatment.Methods:A cross-sectional study was conducted. Clinical information of 544 HIV/acquired immune deficiency syndrome (AIDS) patients who underwent CMV-DNA tests in Beijing Ditan Hospital in 2023 was collected. Participants were categorized into CMV-infection group (126 cases) and non-CMV-infection group (418 cases). The prevalence of CMV infection was analyzed. Univariate and multivariate logistic regression analysis were performed to identify risk factors for CMV/AIDS co-infection. The disease spectrum, laboratory characteristics, serum CMV-DNA load changes, treatment prognosis and outcomes in the CMV-infected group were evaluated. SPSS 27.0 was used for statistical analysis including the χ 2 test, Mann-Whitney U test, and Kruskal-Wallis H test. Results:The CMV infection rate among HIV/AIDS patients was 23.16% (126/544). Multivariate analysis identified low CD4 +T-lymphocyte count [<50 cells/μl; OR=27.962, 95% confidence interval( CI) 11.957-65.389] and high HIV RNA load (>1×10 5 copies/ml; OR=2.057, 95% CI 1.237-3.420) as independent risk factors for CMV co-infection in HIV/AIDS patients. Among the 126 HIV/CMV co-infected patients, CMV viremia was the most common manifestation (38.10%, 48/126), followed by CMV pneumonia (33.33%, 42/126) and CMV retinitis (11.90%, 15/126), which were mainly observed in patients with CD4 +T-lymphocyte counts <50 cells/μl. Of the patients receiving anti-CMV therapy, 80.70% (46/57) exhibited reduced CMV-DNA loads compared with baseline. Totally 29.82% (17/57) of those patients initiating antiretroviral therapy alone achieved CMV-DNA reduction compared with baseline. Overall, 80.16% (101/126) of patients achieved favorable prognosis. Conclusion:CMV co-infection is high in HIV/AIDS patients. Disease spectrum of HIV/CMV co-infection are dominated by CMV viremia and CMV pneumonia. Timely anti-CMV therapy is pivotal for reducing CMV-DNA loads and improving prognosis.

Objective:To explore the interplay between tumor microenvironment (TME)-associated genes, cuproptosis, and the prognosis of liver cancer through transcriptome sequencing and functional genomics analysis.Methods:Employing a hybrid approach that integrates bioinformatics with fundamental experimental research, we utilized the TCGA database to acquireexpression profiles and clinical-pathological information from 424 liver hepatocellular carcinoma patients. We evaluated ImmuneScore and StromalScore to categorize patients into high and low groups, subsequently identifying differentially expressed genes (DEG) at the intersection of these groups. Core DEG were identified through univariate Cox regression analysis and protein-protein interaction (PPI) network analysis. The association between the expression levels of core genes and the survival time of liver cancer patients was analyzed using the R language and Kaplan-Meier analysis, and verified using the Kaplan-Meier Plotter online database. We established a cuproptosis cell model and performed RNA-seq to examine gene expression alterations during copper-induced cell death, followed by in vitro cell experiments for verification.Results:A total of 1 701 and 2 041 DEG were llinked t ImmuneScore and StromalScore, respectively, encompassing 1 134 commonly upregulated genes and 60 commonly downregulated genes. The top 30 core genes from the PPI network's dominant nodes were cross-referenced with univariate Cox regression results, leading to the identification of the pivotal immune gene CCR7. CCR7 mRNA expression levels were higher in hepatocellular carcinoma tissues than in normal tissues ( P<0.05). Patients with high expression of CCR7 in liver cancer had a longer overall survival compared to those with low expression ( P=0.003). Treatment with elesclomol-CuCl2significantly curtailed the survival of hepatocellular carcinoma cel ( P<0.001). RNA-seq data from the cuproptosis model indicated a downregulation of CCR7 expression during the onset of cuproptosis [|log 2(FC)|=2.27, P<0.001], and downregulation of CCR7 expression enhanced the sensitivity of hepatocellular carcinoma cells to cuproptosis inducers. Conclusion:The TME-related gene CCR7 is implicated in cuproptosis, and its downregulation might facilitate the process in liver cancer.CCR7 holds potential as a biomarker for liver cancer prognosis.

AIM:This study aimed to investigate the expression and localization of ALOX12P2 in oral squa-mous cell carcinoma(OSCC),as well as its effects on cell viability,migration,and invasion.METHODS:The expres-sion of ALOX12P2 in head and neck squamous cell carcinoma(HNSCC)tissues and its correlation with clinicopathologi-cal features were analyzed using the UALCAN database(University of Alabama at Birmingham Cancer Data Analysis Por-tal).Additionally,the expression of ALOX12P2 in OSCC and its impact on survival prognosis were evaluated through the GDC and UCSC Xena databases.The expression levels of ALOX12P2 in OSCC cell lines were assessed via quantitative re-al-time PCR(RT-qPCR).The subcellular localization of ALOX12P2 was determined using nucleoplasmic RNA isola-tion.CAL-27 cells were used to establish an ALOX12P2 knockdown group(SS-ALOX12P2)and a control group(SS-NC).HN30 cells were employed to form an ALOX12P2 overexpression group(ALOX12P2)and a control group(vector).The effects of altered ALOX12P2 expression on the epithelial-mesenchymal transition(EMT)-related gene E-cadherin and the PI3K/AKT signaling pathway were assessed through Western blot analysis.RESULTS:ALOX12P2 expression was significantly higher in HNSCC and OSCC tissues compared to normal tissues,with its expression correlating with poor prog-nosis.RT-qPCR analysis indicated that the relative expression of ALOX12P2 in OSCC cells was comparable to that in nor-mal cells(P<0.05).RNA nucleoplasmic isolation confirmed that ALOX12P2 localized in the nucleus.In comparison to the SS-NC group,the SS-ALOX12P2 group exhibited a marked reduction in ALOX12P2 expression(P<0.01),alongside significant decreases in cell viability,migration,and invasion(P<0.01).Conversely,the ALOX12P2 group showed sub-stantially higher relative expression compared to the vector group(P<0.01),with enhanced cell viability,migration,and invasion abilities(P<0.01).Western blot analysis demonstrated that ALOX12P2 knockdown resulted in upregulation of E-cadherin and downregulation of N-cadherin and Vimentin(P<0.01),while overexpression of ALOX12P2 yielded the opposite effects(P<0.01).Knockdown of ALOX12P2 led to decreased protein expression of p-PI3K and p-AKT(P<0.01),whereas overexpression increased these protein levels(P<0.01).CONCLUSION:ALOX12P2 is highly ex-pressed in OSCC and promotes cell viability,migration,and invasion.This effect may be linked to the activation of the PI3K/AKT signaling pathway,which facilitates the epithelial-mesenchymal transition(EMT)process.

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.

Primary liver cancer is one of the leading causes of cancer-related deaths worldwide, its early diagnosis and early treatment are of great clinical importance. The main detection tools for liver cancer include serological indicators, imaging tests and risk assessment models. With the advancement of technology and research, the sensitivity and specificity of laboratory tests for liver cancer have been substantially improved, but there are still false negatives and low rates of early diagnosis. For different causes and prevalence regions, each country has developed its clinical practice guidelines to guide risk groups for effective prevention, early diagnosis and standardized treatment. It is important to establish a liver cancer diagnosis strategy that is suitable for China′s national conditions, concerning the guidelines for the vigilance and prevention of liver cancer. In this article, the advantages and disadvantages of liver cancer-related tests and the impact of future development trends on laboratory strategies are explained from the perspective of laboratory testing strategies, to provide theoretical support for the practical application of liver cancer diagnostic strategies.

Objective:To evaluate the impact of preemptive analgesia with ibuprofen on postoperative pain following the extraction of impacted mandibular third molars in a Chinese population, aiming to provide a clinical reference for its application.Methods:This multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted from April 2022 to October 2023 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), and Beijing Chao-Yang Hospital, Capital Medical University (20 cases). It included 82 patients with impacted mandibular third molars, with 41 in the ibuprofen group and 41 in the control group. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups were instructed to take sustained-release ibuprofen capsules as planned for 3 days post-surgery. Pain intensity was measured using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h after surgery, and the use of additional analgesic medication was recorded during days 4 to 6 postoperatively.Results:All 82 patients completed the study according to the protocol. No adverse events such as nausea, vomiting, or allergies were reported in either group during the trial. The ibuprofen group exhibited significantly lower pain scores at 4 h [2.0 (1.0, 4.0) vs. 4.0 (3.0, 5.0)] ( Z=-3.73, P<0.001), 6 h [2.0 (1.0, 4.0) vs. 5.0(2.5, 6.0)] ( Z=-3.38, P<0.001), and 8 h [2.0 (1.0, 4.0) vs. 5.0 (2.0, 6.0)] ( Z=-2.11, P=0.035) postoperatively compared to the control group. There were no statistically significant differences in pain scores between the groups at 30 min, 24 h, 48 h, and 72 h postoperatively ( P>0.05). Additionally, 11 out of 41 patients (26.8%) in the ibuprofen group and 23 out of 41 patients (56.1%) in the control group required extra analgesic medication between days 4 and 6 post-surgery, with the ibuprofen group taking significantly fewer additional pills [0.0 (0.0, 1.0) vs. 1.0 (0.0, 3.0)] ( Z=-2.81, P=0.005). Conclusions:A pain management regimen involving 300 mg of oral sustained-release ibuprofen capsules administered 15 minutes before surgery and continued for 3 d postoperatively effectively reduces pain levels and the total amount of analgesic medication used after the extraction of impacted mandibular third molars. Considering its efficacy, safety, and cost-effectiveness, ibuprofen is recommended as a first-line drug for perioperative pain management, enhancing patient comfort during diagnosis and treatment in a feasible manner.

Objective:To understand the status quo of the job preparedness among newly recruited nurses and analyze its influencing factors.Methods:Totally 355 newly recruited nurses who joined 5 Class Ⅲ Grade A hospitals nationwide between September 2021 and September 2022 were selected by convenience sampling and investigated by general information surveys, the Work Readiness Scale for Graduate Nurses and the Transition Shock of Newly Graduated Nurses Scale. Logistic regression was employed to analyze the influencing factors of the job preparedness among these newly recruited nurses.Results:A total of 355 questionnaires were distributed, and 350 valid responses were received, with a valid response rate of 98.6%. The overall score for the job preparedness of the newly recruited nurses was (271.05±49.97), with a standardized total score of (73.26±13.57). 208 individuals (59.4%) scored high (standardized total score ≥70), while 142 individuals (40.6%) scored low (standardized total score<70). Logistic regression analysis revealed that the department of employment, part-time job experience, harmonious relationships with classmates during schooling, and the level of transition shock were influencing factors for the job preparedness of the newly recruited nurses ( P<0.05) . Conclusions:The job preparedness of newly recruited nurses is influenced by various factors. Nursing educators and managers should adopt targeted educational and management strategies based on the nurses' different experiences, interpersonal relationships, department of employment, and level of transition shock to enhance their job preparedness.

Cholestatic liver disease is a common disease that causes bile flow dysfunction due to various reasons. The etiology of cholestatic liver disease is complexed, and therapeutic drugs are extremely limited. To date, ursodeoxycholic acid is the only FDA-approved drug for treating primary biliary cirrhosis, whereas its efficacy is limited to early stage of the disease, therefore novel drugs are urgently needed. Nuclear receptors become therapeutic hotspot target in cholestasis since these receptors play a key role in regulating bile acid homeostasis. Peroxisome proliferator-activated receptor (PPAR) is an important nuclear receptor involved in regulating multiple mechanisms of cholestasis in vivo. It can improve intrahepatic cholestasis by inhibiting bile acid synthesis, reducing bile acid toxicity, affecting the expression of bile acid metabolic enzymes and transporters, and can play an anti-inflammatory, anti-oxidation and anti-fibrosis role. A number of studies have shown that PPAR agonists represented by fibrates alone or in combination can improve liver function indexes, inflammatory factors and fibrosis markers in patients with cholestasis. This review analyzes and summarizes the lastest advances in the molecular mechanism of PPAR as a therapeutic target for cholestasis and drug treatment in development or have been used in clinical.