Objective： To investigate the relationship between the lipid metabolism-related gene sterol carrier protein 2(SCP2) and prostate cancer (PCa) from a multi-omics perspective using single-cell transcriptomes combined with Mendelian randomization. Methods： Single-cell transcriptome data of benign and malignant prostate tissues were obtained from GSE120716, GSE157703 and GSE141445 datasets, respectively. Integration, quality control and annotation were performed on the data to categorize the epithelial cells into high and low SCP2 expression groups, followed by further differential and trajectory analyses. Single nucleotide polymorphism (SNP) data for SCP2 expression quantitative trait loci (eQTL) were subsequently downloaded from Genotype-Tissue Expression (GTEx) and investigated from the PCa Society Cancer-Related Genomic Alteration Panel for the Investigation of Cancer-Related Alterations (PRACTICAL) to obtain PCa outcome data for Mendelian randomization analysis to validate the causal relationship between SCP2 and PCa. Results： High SCP2-expressing epithelial cells had higher energy metabolism and proliferation capacity with low immunotherapy response and metastatic tendency. Trajectory analysis showed that epithelial cells with high SCP2 expression may have a higher degree of malignancy, and SCP2 may be a key marker gene for differentiation of malignant epithelial cells in the prostate. Further Mendelian randomization results showed a significant causal relationship between SCP2 and PCa development (OR=1.045, 95% CI: 1.010 －1.083, P=0.011). Conclusion： By combining single-cell transcriptome and Mendelian randomization, the role of the lipid metabolism-related gene SCP2 in PCa development has been confirmed, and new targets and therapeutic directions for PCa treatment have been provided.
Humans ; Prostatic Neoplasms/genetics* ; Male ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Single-Cell Analysis ; Sequence Analysis, RNA ; Carrier Proteins/genetics* ; Transcriptome ; Lipid Metabolism

ObjectiveObesity has been identified as one of the most important risk factors for cognitive dysfunction. Physical exercise can ameliorate learning and memory deficits by reversing synaptic plasticity in the hippocampus and cortex in diseases such as Alzheimer’s disease. In this study, we aimed to determine whether 8 weeks of treadmill exercise could alleviate hippocampus-dependent memory impairment in high-fat diet-induced obese mice and investigate the potential mechanisms involved. MethodsA total of sixty 6-week-old male C57BL/6 mice, weighing between 20-30 g, were randomly assigned to 3 distinct groups, each consisting of 20 mice. The groups were designated as follows: control (CON), high-fat diet (HFD), and high-fat diet with exercise (HFD-Ex). Prior to the initiation of the treadmill exercise protocol, the HFD and HFD-Ex groups were fed a high-fat diet (60% fat by kcal) for 20 weeks. The mice in the HFD-Ex group underwent treadmill exercise at a speed of 8 m/min for the first 10 min, followed by 12 m/min for the subsequent 50 min, totally 60 min of exercise at a 0° slope, 5 d per week, for 8 weeks. We employed Y-maze and novel object recognition tests to assess hippocampus-dependent memory and utilized immunofluorescence, Western blot, Golgi staining, and ELISA to analyze axon length, dendritic complexity, number of spines, the expression of c-fos, doublecortin (DCX), postsynaptic density-95 (PSD95), synaptophysin (Syn), interleukin-1β (IL-1β), and the number of major histocompatibility complex II (MHC-II) positive cells. ResultsMice with HFD-induced obesity exhibit hippocampus-dependent memory impairment, and treadmill exercise can prevent memory decline in these mice. The expression of DCX was significantly decreased in the HFD-induced obese mice compared to the control group (P<0.001). Treadmill exercise increased the expression of c-fos (P<0.001) and DCX (P=0.001) in the hippocampus of the HFD-induced obese mice. The axon length (P<0.001), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P<0.001) in the hippocampus were significantly decreased in the HFD-induced obese mice compared to the control group. Treadmill exercise increased the axon length (P=0.002), dendritic complexity(P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P=0.001) of the hippocampus in the HFD-induced obese mice. Our study found a significant increase in MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of HFD-induced obese mice compared to the control group. Treadmill exercise was found to reduce the number of MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of obese mice induced by a HFD. ConclusionTreadmill exercise led to enhanced neurogenesis and neuroplasticity by increasing the axon length, dendritic complexity, dendritic spine numbers, and the expression of PSD95 and DCX, decreasing the number of MHC-II positive cells and neuroinflammation in HFD-induced obese mice. Therefore, we speculate that exercise may serve as a non-pharmacologic method that protects against HFD-induced hippocampus-dependent memory dysfunction by enhancing neuroplasticity and neurogenesis in the hippocampus of obese mice.

This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

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Objective:To investigate the correlation between imaging features of mixed ground-glass nodules(mGGNs)under dual lung enhanced CT and pathological subtypes of lung adenocarcinoma.Methods:Retrospective analysis of clinical data of 102 isolated mGGN lung adenocarcinoma patients admitted to Dalian Central Hospital from October 2016 to October 2018.The patients were divided into adenocarcinoma in situ(AIS)group,minimally invasive adenocarcinoma(MIA)group and invasive adenocarcinoma(IAC)group according to postoperative pathological examination results.Measure the maximum diameter lesions,the maximum diameter of solid components and the proportion of solid components to evaluate imaging features of three groups.The relationship between pathological subtypes of lung adenocarcinoma and baseline features,imaging features,mGGN lesions,maximum diameter of solid components and proportion of solid components were analyzed.The diagnostic value of the maximum diameter of lesions,the maximum diameter of solid components,and the proportion of solid components in IAC were analyzed by receiver operating characteristic(ROC)curves.Results:102 patients were divided into AIS group(n=20),MIA group(n=29)and IAC group(n=53)based on postoperative pathological diagnosis.There was a statistically significant difference in age among the three groups(P＜0.05).Tumor distribution locations:35 cases in the upper lobe of the right lung,10 cases in the middle lobe of the right lung,and 15 cases in the lower lobe of the right lung;23 cases in the upper lobe of the left lung and 19 cases in the lower lobe of the left lung,the tumor distribution locations in the upper lobe of the right lung was relatively high in various pathological subtypes.The lesions in AIS and MIA groups were mostly circular or elliptical in shape,whiile the lesions in the IAC group was mostly irregular in shape.There was a statistically significant difference in morphological comparisons among the three groups(P＜0.05).There was a statistically significant difference in burr sign between MIA group and IAC group(P＜0.05).There was a statistically significant difference in pleural indentation sign and bronchial inflation sign between MIA group and IAC group(P＜0.05).There was a statistically significant difference in the maximum diameter of lesions and the maximum diameter of solid components among the three groups(P＜0.05).The proportion of solid components in IAC group was higher than that in AIS and MIA groups,and the difference was statistically significant(P＜0.05).The ROC curve shows that,the area under curve(AUC)for diagnosing IAC based on the maximum diameter of the lesion,the maximum diameter of the solid component,and the proportion of the solid component were 0.840,0.966 and 0.816,respectively.The AUC of diagnosing IAC with the maximum diameter of the solid component was greater than the AUC of the maximum diameter of the lesion and the proportion of solid components(P＜0.05).Conclusion:Dual lung enhanced CT can evaluate the imaging features of mGGN,and it can distinguish the pathological subtypes of lung adenocarcinoma,when the maximum diameter of the lesion is ≥ 16.5 mm,the maximum diameter of the solid component is ≥5.5 mm,or the proportion of solid component is ≥47.00％,it can effectively diagnose IAC,the maximum diameter of solid components has the best diagnostic efficiency for IAC.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

Objective To explore the factors that influence major adverse cardiovascular events(MACE)in atrial fibrillation(AF)patients undergoing radiofrequency ablation(RFA),as well as to compare the prognosis of patients with advanced AF to that of the general population.Methods We prospectively recruited AF patients who underwent RFA treatment at Peking University Third Hospital between January 2021 and March 2023.General patient data were collected through the hospital's inpatient system,and MACE were tracked through outpatient visits and telephone follow-ups.Patients were categorized into three age groups:Group 1(under 65 years),Group 2(65 to 75 years),and Group 3(over 75 years).In this study,MACE was defined as include cardiovascular death,all-cause death,readmission for heart failure,acute coronary syndrome(ACS),grade 2 or higher bleeding and stroke.Results A total of 431 patients were included in this study,with an average age of(66.17±12.22)years.Among these patients,259 were male(60.09％),and the mean of CHA2DS2-VASc score was(1.79±1.30).The median follow-up period was 16.0(11.3,21.3)months,during which 28(6.50％)patients experienced MACE,with ACS and stroke being the most common events.Variables were selected using LASSO regression,and a LASSO-Cox regression model was constructed.Age(HR 1.06,95％CI 1.02-1.10,P=0.006)and hypertrophic cardiomyopathy(HR 3.70,95％CI 1.27-8.68,P=0.008)were identified as independent predictors of MACE after RFA for AF.Subgroup analysis revealed that patients under 65 had significantly better prognoses compared to older AF patients(P=0.030 compared with group 2;P=0.021 compared with group 3).Conclusions Age and hypertrophic cardiomyopathy are independent risk factors for MACE in AF patients undergoing RFA.The prognosis for younger patients is better than that for older patients,while the prognosis for advanced patients is comparable to that of patients aged 65-75 years.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

Objective To explore the factors that influence major adverse cardiovascular events(MACE)in atrial fibrillation(AF)patients undergoing radiofrequency ablation(RFA),as well as to compare the prognosis of patients with advanced AF to that of the general population.Methods We prospectively recruited AF patients who underwent RFA treatment at Peking University Third Hospital between January 2021 and March 2023.General patient data were collected through the hospital's inpatient system,and MACE were tracked through outpatient visits and telephone follow-ups.Patients were categorized into three age groups:Group 1(under 65 years),Group 2(65 to 75 years),and Group 3(over 75 years).In this study,MACE was defined as include cardiovascular death,all-cause death,readmission for heart failure,acute coronary syndrome(ACS),grade 2 or higher bleeding and stroke.Results A total of 431 patients were included in this study,with an average age of(66.17±12.22)years.Among these patients,259 were male(60.09％),and the mean of CHA2DS2-VASc score was(1.79±1.30).The median follow-up period was 16.0(11.3,21.3)months,during which 28(6.50％)patients experienced MACE,with ACS and stroke being the most common events.Variables were selected using LASSO regression,and a LASSO-Cox regression model was constructed.Age(HR 1.06,95％CI 1.02-1.10,P=0.006)and hypertrophic cardiomyopathy(HR 3.70,95％CI 1.27-8.68,P=0.008)were identified as independent predictors of MACE after RFA for AF.Subgroup analysis revealed that patients under 65 had significantly better prognoses compared to older AF patients(P=0.030 compared with group 2;P=0.021 compared with group 3).Conclusions Age and hypertrophic cardiomyopathy are independent risk factors for MACE in AF patients undergoing RFA.The prognosis for younger patients is better than that for older patients,while the prognosis for advanced patients is comparable to that of patients aged 65-75 years.