Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*

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.

With the rapid development of medical big data and artificial intelligence,Clinical Prediction Models(CPMs)have become pivotal tools for disease prevention,diagnosis,and treatment.Current research predominantly focuses on the economic analysis of pharmacological or public health interventions,yet a comprehensive methodological framework for the economic evaluation of CPMs has been notably absent.The Guidelines for Economic Evaluation of Clinical Prediction Models(hereafter the Guidelines),jointly initiated by the Chinese Research Hospital Association and Peking University,Tsinghua University,and Capital Medical University,adheres to the WHO Handbook for Guideline Development and the Reporting Items for Practice Guidelines in Healthcare(RIGHT)standards.A multidisciplinary collaboration,including a steering committee,expert panel,secretariat,and external review group,was established to develop the guideline following evidence-based principles and procedures.Consensus recommendations were formulated through the Delphi method.It describes the background,objectives,target group,and the development methodology and process,ensuring the entire compilation process of the Guidelines is transparent and standardized.Through comprehensive evidence retrieval,systematic evidence appraisal,and a scientific approach to forming recommendations,the scientific rigor and validity of the Guidelines were further enhanced.

Objective To evaluate the application effect of perioperative cluster nursing interventions in patients under-going robot-assisted radical prostatectomy.Methods A total of 122 prostate cancer patients who underwent robot-assisted sur-gery from January 2023 to December 2024 were divided into the control group(routine care,55 cases)and the observation group(cluster nursing,67 cases)according to the nursing methods.The psychological status,surgery-related indicators,postoperative recovery,incidence of perioperative complications,and patient satisfaction were compared between the two groups.Results The observation group demonstrated a statistically significant decrease in postoperative anxiety and depression scores compared to the control group(P=0.034,P=0.005).The observation group exhibited shorter operative time and less intraoperative blood loss,with both differences being statistically significant(P=0.016,P＜0.001).In terms of postoperative recovery,the obser-vation group showed faster recovery of bowel function,shorter time for catheter insertion and postoperative hospital stay compared to the control group(P=0.010,P＜0.001,P＜0.001).In the observation group,the incidence of systemic postoperative in-fection was lower than that of the control group(4.5％vs 18.2％,P=0.015).The perioperative hypothermia rate in the obser-vation group was lower than that of the control group(38.8％vs 60.0％,P=0.020).There was no statistically significant difference in postoperative urinary fistula rate between the two groups(P=0.477).The observation group achieved an overall patient satisfaction rate of 98.51％,with higher satisfaction scores compared to the control group(P=0.008).Conclusion Perioperative cluster nursing measures yield favorable outcomes in patients undergoing robot-assisted radical prostatectomy.It can not only shorten the operation time,promote the postoperative recovery of patients,but also reduce the anxiety and depression of patients and complica-tions,and improve patient satisfaction.

Objective:To investigate the predictive value of serum signal lymphocyte activation molecule family member 8(SLAMF8)levels for post-stroke cognitive impairment(PSCI).Methods:The GSE122063 dataset was selected from the Gene Expression Omnibus(GEO), and key genes associated with vascular dementia were identified using STRING network and Cytoscape software.This prospective cohort study involved 123 patients with acute cerebral infarction(ACI)who were admitted to the Department of Neurology at Jiangsu University Affiliated Hospital from January to December 2023.Patients were followed up for six months and categorized into PSCI and post-stroke non-cognitive impairment(PSNCI)groups based on the occurrence of PSCI.General data from both groups at baseline, as well as the Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment Scale(MoCA)scores at the six-month follow-up, were collected.Baseline serum levels of SLAMF8 and stabilin-1(STAB1), along with serum levels of interleukin-1β(IL-1β)and interleukin-6(IL-6)at the six-month follow-up, were measured.Pearson correlation analysis was used to assess the correlation between variables, while logistic regression analysis was employed to determine baseline factors influencing the occurrence of PSCI.Receiver Operating Characteristic(ROC)curves were plotted to analyze the predictive value of variables for PSCI occurrence.Results:The Cytoscape software identified SLAMF8 and STAB1 as key genes associated with vascular dementia, utilizing maximum neighborhood component density(DNMC)and eccentricity algorithms on the GSE122063 dataset.In the cohort study, patients in the PSCI group exhibited higher baseline NIHSS scores and serum SLAMF8 levels compared to the PSNCI group( t=3.033, 5.422; P<0.01). Additionally, they demonstrated significantly lower MMSE and MoCA scores( t=16.340, 18.634; P<0.001)and higher serum levels of IL-1β and IL-6( t=2.633, 2.632; P<0.05)at the 6-month follow-up.No significant difference was observed in baseline STAB1 levels between the two groups( t=1.280, P>0.05). In the PSCI group, there was no significant correlation between baseline serum SLAMF8 levels and admission NIHSS scores( r=0.257, P=0.082); however, SLAMF8 showed a negative correlation with both MMSE scores( r=-0.711, P<0.001)and MoCA scores( r=-0.686, P<0.001)at the 6-month follow-up.Logistic regression analysis indicated that baseline serum SLAMF8 levels( OR=1.142, P=0.001)and NIHSS scores( OR=1.094, P=0.007)were risk factors for the development of PSCI in patients with acute cerebral infarction(ACI). ROC curve analysis revealed that the area under the ROC curve(AUC)for baseline serum SLAMF8 levels in predicting PSCI occurrence in ACI patients was 0.776, while the AUC for the combined prediction using both SLAMF8 and NIHSS scores was 0.796.Furthermore, baseline serum SLAMF8 levels were positively correlated with serum IL-1β levels( r=0.652, P<0.001)and IL-6 levels( r=0.710, P<0.001)at the 6-month follow-up. Conclusions:The serum SLAMF8 level, exhibiting early high expression in ACI patients, may serve as a potential biological marker for predicting the occurrence of PSCI.

Objective:To investigate the potential causal relationships between gut microbiota composition and the risk of developing various subtypes of breast cancer by using bidirectional two-sample Mendelian randomization(MR).Methods:The research utilized genome-wide association studies(GWAS) data on gut microbiota from the MiBioGen database and GWAS data on breast cancer from the Breast Cancer Association Consortium (BCAC). In this MR study, inverse variance weighted (IVW), weighted median, MR Egger, and MR-PRESSO methods were used. Additionally, reverse MR and stratified analyses were conducted to assess reverse causality and the impact on different subtypes of breast cancer.Results:Adlercreutzia (IVW OR=0.92, 95% CI: 0.87-0.98, P=0.01) and Parabacteroides (IVW OR=0.87, 95% CI: 0.79-0.96, P=0.007) exhibited a statistically significant protective effect on breast cancer. Conversely, Sellimonas (IVW OR=1.05, 95% CI: 1.01-1.09, P=0.01) was significantly associated with an increased risk of breast cancer. Desulfovibrio (IVW OR=0.94, 95% CI: 0.88-1.00, P=0.04) and Ruminococcaceae (UCG013) (IVW OR=0.92, 95% CI: 0.86-0.99, P=0.03) presented suggestive protective effects against breast cancer. Furthermore, stratified analysis revealed that the protective effect of Adlercreutzia against breast cancer persisted in the estrogen receptor(ER)-positive subtypes, while Desulfovibrio persisted in the ER-negative subtypes. Sellimonas was causally associated with the risk of ER-positive subtypes. CACNA1S was identified as the functional gene of Adlercreutzia, and associated with favorable prognosis in breast cancer, while ERBB4 was identified as the functional gene of Sellimonas and associated with poor prognosis in breast cancer. Conclusions:This study identifies the causal relationships between gut microbiota and breast cancer, suggesting a novel target for early clinical intervention and treatment, with potential implications for future functional analysis.

Objective:Based on bioinformatics analysis, this study aimed to identify the complement component 5a receptor 1(C5aR1)and chemokine C-C motif ligand-2(CCL2)genes in vascular dementia(VaD)and to explore the expression and clinical significance of serum C5aR1 and CCL2 levels in VaD patients.Methods:The GSE122063 dataset was selected from the Gene Expression Omnibus(GEO)database to screen for consistently differentially expressed genes in the frontal and temporal lobes of VaD patients and non-dementia patients.The Matascape database was used to analyze the functions and pathways of differentially expressed genes, and the STRING network and Cytoscape software were used to identify key genes.In this case-control study, 53 VaD patients seeking care at the Department of Neurology of the Affiliated Hospital of Jiangsu University between January 2022 and December 2022 were included in the VaD group, and 50 non-dementia individuals were included in the control group.General information, Montreal Cognitive Assessment(MoCA)scores, Mini-Mental State Examination(MMSE)scores, and scores of the total cerebral small vessel disease(CSVD)burden were collected for both groups, and serum C5aR1 and CCL2 expression was detected.The correlation of serum C5aR1 and CCL2 levels with MoCA scores, MMSE scores, and scores of the total CSVD burden in the VaD group was analyzed.Receiver operating characteristic(ROC)curve analysis was used to assess the diagnostic value of serum C5aR1 and CCL2 levels in VaD.Results:In the GSE122063 dataset, compared with non-dementia patients, there were 43 upregulated genes and 63 downregulated genes simultaneously in the frontal and temporal lobes in the VaD group.After importing 106 genes into the Cytoscape software and using the Stress and Betweenness algorithms in the cytoHubba plugin, two key genes, C5aR1 and CCL2, were identified.Serum levels of C5aR1[(57.25±10.34)μg/L vs.(43.26±8.24)μg/L, t=7.607, P<0.001]and CCL2[(210.42±42.19)ng/L vs.(151.73±36.04)ng/L, t=7.570, P<0.001]in the VaD group were higher than those in the control group.Serum levels of C5aR1 and CCL2 were negatively correlated with MoCA scores( r=-0.691, -0.668, P<0.001)and MMSE scores( r=-0.736, -0.729, P<0.001), and positively correlated with scores of the total CSVD burden( r=0.598, 0.582, P<0.001).The areas under the ROC curve for serum C5aR1 and CCL2 levels in diagnosing VaD was 0.838 and 0.845, respectively.The area under the ROC curve with the combination of C5aR1 and CCL2 for the diagnosis of VaD was 0.896. Conclusions:Serum levels of C5aR1 and CCL2 are elevated in VaD patients and closely related to their cognitive function and the total CSVD burden, and may be used as an auxiliary diagnostic tool for VaD patients.

Objective The aim of this study is to discuss the causal relationship between periodontal disease(PD)and prostate cancer(PCa).Methods A two-sample bidirectional Mendelian randomization(MR)analysis based on publicly statistical data from genome-wide association studies(GWAS)was conducted.MR Egger,weighted medium,simple mode and weighted mode were supplemented,while inverse variance weighted analysis(IVW)was the main method of analysis.Heterogeneity testing,pleiotropy testing and leave-one-out testing were used to assess the sensitivity and stabili-ty.Results The results of MR analysis showed that PD had no significant impact on the occurrence of PCa:East Asian(IVW,PD:OR=1.07,P=0.48);European(IVW,PD:OR=1.00,P=0.37,periodontitis:OR=1.03,P=0.14,chronic gingivitis:OR=0.99,P=0.37,chronic periodontitis:OR=1.03,P=0.22).The reverse MR analysis also did not show a causal relationship between PCa and PD:East Asian(IVW,PD:OR=0.97,P=0.22);European(IVW,PD:OR=0.84,P=0.44,periodontitis:OR=1.01,P=0.75,chronic gingivitis:OR=0.93,P=0.23,chronic periodontitis:OR=0.99,P=0.80).The results of other analysis were consistent with those of IVW analysis.Conclusions The results of our two-sample bidirectional MR analysis do not support a causal relationship between PD and PCa.

Objective To investigate the impact of various health education intervention strategies on the proper use of personal respiratory protective equipment (RPE) among workers exposed to dust. Methods Dust-exposed workers were recruited from 60 selected enterprises in Guangdong Province using cluster random sampling method. They were randomly allocated to the control, low-intensity intervention, and high-intensity intervention groups, with 358, 346, and 371 workers in each group, respectively. Workers in the control group received no designed intervention. Workers in the low-intensity intervention group received traditional plus mobile health education on the proper use of RPE. Workers in the high-intensity intervention group received all components of the low-intensity intervention, supplemented with peer education. The intervention lasted for six months. RPE usage was compared among the three groups of workers before and after the intervention. Results Workers in the control, low-intensity intervention, and high-intensity intervention groups showed higher rates of both RPE wearing and correct RPE wearing after the intervention than before it within their respective groups (RPE wearing rate: 94.1% vs 99.2%, 95.7% vs 100.0%, 94.6% vs 100.0%, all P<0.01; correct RPE wearing rate: 66.8% vs 91.1%, 67.3% vs 95.7%, 66.6% vs 96.5%, all P<0.01). Post-intervention correct RPE wearing rates were highest in the high-intensity intervention group, followed by the low-intensity intervention group, and the control group, with the percentage of 96.50%, 95.66% and 91.06%, respectively (P<0.01). Binary logistic regression analysis result showed that different intervention strategies affected the correct use of personal RPE among dust-exposed workers after adjusting for gender, age, and other confounding factors (P<0.05). Compared with the control group, the rates of correct RPE use increased in the low-intensity intervention group and the high-intensity intervention group (odd ratio was 2.14 and 3.01; 95% confidence interval was 1.12 - 4.10 and 1.53 - 5.91, respectively). Conclusion The implementation of traditional plus mobile health education interventions on the proper use of RPE can promote correct RPE utilization among dust-exposed workers, and integrating peer education further enhances the intervention effectiveness.

Objective To explore the diagnostic value of endoscopic grading of gastric intestinal metaplasia (EGGIM) score under acetic acid-enhanced narrow band imaging (AA-NBI) observation mode for gastric intestinal metaplasia (GIM). Methods A total of 120 patients who underwent gastroscopy at Jinshan Hospital of Fudan University from February 2022 to February 2023 were selected. All patients underwent both white light and AA-NBI endoscopy, with photographic records of intestinal metaplasia in five areas: greater curvature of antrum, lesser curvature of antrum, greater curvature of corpus, lesser curvature of corpus and incisura. EGGIM score was performed: 0 for no intestinal metaplasia, 1 point for focal intestinal metaplasia (GIM area ratio≤30%), 2 points for extensive intestinal metaplasia (GIM area ratio＞30%), with a total score of 10 points. Targeted biopsies were performed on suspicious GIM lesions found during endoscopy. If no suspicious GIM lesions were observed, random biopsies were performed according to the updated Sydney system. The pathological histological examination results were staged based on the operative link on gastric intestinal metaplasia assessment (OLGIM) system. The diagnostic value of EGGIM score for OLGIM stage Ⅲ-Ⅳ patients was evaluated using receiver operating characteristic (ROC) curves. Results The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of AA-NBI in detecting GIM were 96.3%, 91.6%, 94.5%, 95.0%, and 93.6%, respectively. The area under the ROC curve for EGGIM diagnosing OLGIM stage Ⅲ-Ⅳ was 0.952 (95%CI 0.914-0.990). The optimal cut-off value for EGGIM was 5 points, with a sensitivity of 96.7% (95%CI 87.6%-99.4%) and specificity of 88.1% (95%CI 76.5%-94.7%). Conclusions EGGIM score (≥5 points) under AA-NBI mode has good diagnostic capability for patients with OLGIM stage Ⅲ-Ⅳ.