Cognitive dysfunction often occurs in Alzheimer's disease, Parkinson's disease, cerebrovascular disease, or other neurodegenerative diseases, and can significantly impact the life quality of patients and create serious social, psychological, and economic burdens for individuals and their families. Numerous studies have confirmed that exercise can slow the decline in cognitive function through multiple pathways, in which fibronectin type III domain-containing protein 5 (FNDC5) plays an important role. However, the current research on the modulation of FNDC5 by exercise and its ability to improve hippocampal cognitive function lacks a systematic and comprehensive understanding. Therefore, this review focuses on the latest research progress regarding the role of exercise-induced FNDC5 in cognitive function, systematically reviews the positive effects of FNDC5 on cognitive function impairment caused by various factors, and clarifies the specific mechanisms by which exercise-induced FNDC5 improves cognitive function by inhibiting neuroinflammation and improving hippocampal neurogenesis and hippocampal synaptic plasticity. Based on the existing literature, we also identify the areas that require further research in this field. Overall, this review provides a theoretical basis for exercise-based prevention and improvement of cognitive function impairment.
Humans ; Cognition/physiology* ; Fibronectins/physiology* ; Exercise/physiology* ; Hippocampus/physiology* ; Cognitive Dysfunction/prevention & control* ; Neuronal Plasticity ; Animals ; Neurogenesis

Objective:To explore the role of long noncoding RNA(lncRNA) CCDC18-AS1 in parathyroid carcinoma(PC) diagnosis.Methods:This cross-sectional study included 55 patients with primary hyperparathyroidism treated at Beijing Shijitan Hospital from 2013 to 2024. Of these, 12 patients were diagnosed with PC and 43 with parathyroid adenoma(PA). Tissue samples and clinical data were collected, and lncRNA CCDC18-AS1 expression were measured using real-time quantitative PCR(RT-qPCR).Results:LncRNA CCDC18-AS1 expression was significantly higher in the PC group than that in the PA group( P=0.003). It was identified as an independent risk factor for PC, independent of age, sex, or serum calcium levels. Among patients with hypophosphatemia, no significant differences in lncRNA CCDC18-AS1 expression was observed between the PC and PA groups. However, in patients with normal serum phosphate levels, lncRNA CCDC18-AS1 expression was significantly higher in the PC group( P<0.001) and showed a positive correlation with serum phosphorus concentration( P=0.001). The area under the receiver operating characteristic(ROC) curve(AUC) for lncRNA CCDC18-AS1 in PC diagnosis was 0.758(95% CI 0.620-0.866, P=0.005), comparable to that of lncRNA plasmacytoma variant translocation 1(PVT1). Among patients with normal serum phosphate, the AUC for lncRNA CCDC18-AS1 increased to 0.969(95% CI 0.835-0.999, P<0.001), with 100% sensitivity and 92.31% specificity, suggesting superior diagnostic performance compared to PVT1(0.840, 95% CI 0.653-0.950, P=0.001). Conclusions:LncRNA CCDC18-AS1 may serves as a potential biomarker for PC diagnosis, with greater diagnostic value in patients with normal serum phosphorus levels.

Objective To explore the value of CT radiomics analysis in predicting the curative effect of extracorporeal shock wave lithotripsy(ESWL)in ureteral calculus(UC)patients.Methods A total of 126 UC patients who underwent ESWL from January 2018 to December 2023 were selected,and randomly divided into training group and validation group at a ratio of 7∶3.Forty-five UC patients from January 2024 to September 2024 were selected as external validation group and divided into two groups according to whether the residual stones were less than 4 mm after operation.There were 81 cases in the successful lithotripsy group and 45 cases in the failed lithotripsy group.The 3D Slicer software was used to outline the stone layer by layer to obtain region of interest(ROI),and 851 radiomics features were extracted.After the observer consistency test,maximum relevance and minimum redundancy(mRMR)algorithm and least absolute shrinkage and selection operator(LASSO),the radiomics features were selected,and the logistic regression model was established.The diagnostic efficiency of the model was analyzed by receiver operating characteristic(ROC)curve.Results The six optimal features were obtained from the radiomics features.The combined clinical-radiomics model showed the best prediction efficiency with area under the curve(AUC)of 0.908,0.906 and 0.908 in the training,validation and external validation groups respectively.Conclusion CT radiomics model can be used to predict the curative effect of UC patients after ESWL,and provide a basis for assisting UC patients in individualized treatment.

Objective To observe conventional color Doppler ultrasound(CDU)and contrast-enhanced ultrasound(CEUS)manifestations of solitary abdominal mass-forming lymphoma.Methods Thirty-two patients with solitary abdominal mass-forming lymphoma confirmed by pathology who underwent CDU examination were retrospectively included,among them 28 patients also received CEUS.CDU manifestations of lesions were observed,including the size,echogenicity,shape,margin,posterior acoustic features,blood flow,as well as presence of cord-like and reticular high echogenicity and vascular encasement or not.The enhancement distribution,degree and pattern of lesion during CEUS were recorded.Results CDU showed that solitary abdominal mass-forming lymphomas lesions mainly appeared as hypoechoic masses with heterogeneous internal echogenicity(24/32,75.00%),irregular shape(28/32,87.50%),clear margin(26/32,81.25%)and posterior acoustic enhancement(28/32,87.50%),with rich blood flow(Adler gradeⅡ—Ⅲ in 24 of 32,75.00%).Vascular encasement and reticular septation were noticed each in 8 cases(8/32,25.00%).During CEUS,peak intensity of contrast agents appeared rapidly in arterial phase,with common high enhancement(26/28,92.86%),which then washed out quickly after the peak or decreased slowly in arterial phase and low enhancement in venous phase.Diffuse distribution(26/28,92.86%),uniform enhancement pattern(20/28,71.43%)and absence of liquefied necrotic area inside(22/28,78.57%)were common findings.Conclusion CDU and CEUS manifestations of solitary abdominal mass-forming lymphoma had characteristics to a certain degree,which might be helpful to early diagnosis.

Objective·To investigate the mechanisms by which different subtypes of G protein-coupled receptor kinases(GRKs)regulate the biased signaling transduction mediated by the muscarinic acetylcholine receptor 1(M1 receptor),focusing on their molecular effects in modulating the binding of the M1 receptor to the downstream heterotrimeric G protein(Gαq-Gβ1-Gγ2)andβ-arrestin 2(βarr2).Methods·By establishing a highly sensitive protein interaction detection system based on bioluminescence resonance energy transfer(BRET),six M1 receptor agonists/allosteric modulators were selected to measure the dynamic interactions between the M1 receptor and four GRK subtypes(GRK2/3/5/6),βarr2,and the G protein under stimulation.All BRET data were statistically quantified using the area under the curve(AUC)of the time-response curves.First,concentration-effect curves were established by treatment with gradient concentrations of agonists/allosteric modulators and AUC fitting,to comprehensively analyze the differences in efficacy between each agonist/allosteric modulator and the endogenous agonist acetylcholine chloride(ACh)in promoting the interactions of M1 receptor with GRK3/5,βarr2,and the G protein;next,GRKs were divided into two groups based on subtypes:GRK2/3 and GRK5/6.The maximum AUC values for the interaction between the M1 receptor and the two GRK groups under high concentrations were calculated respectively,to further evaluate the regulatory propensity of different types of GRKs on the binding strength of the M1 receptor to βarr2 or the G protein.Results·All six agonists/allosteric modulators effectively induced the association of the M1 receptor with GRK3,while simultaneousey inducing dissociation of the M1 receptor from GRK5.The allosteric modulator BQCA not only activated the M1 receptor alone and triggered its binding to downstream signaling proteins,but also,when co-treated with ACh,caused a significant leftward shift of the concentration-effect curves in the M1-G protein and M1-βarr2 systems,suggesting that its potentiation effect on ACh was mainly achieved by reducing the half-maximal effective concentration.A moderate positive correlation was observed between the maximum AUC values of M1-βarr2 and M1-G protein interactions induced by the seven groups of drug treatments(r=0.722,P=0.067).Further analysis showed that the ratio of the maximum AUC for M1-GRK2/3 interaction to that for M1-GRK5/6 interaction was also positively correlated with the ratio of the maximum AUC for M1-βarr2 interaction to that for M1-G protein interaction(r=0.760,P=0.047).Conclusion·The M1 receptor may be pre-coupled with GRK5/6 under basal conditions,and they dissociate upon receptor activation,suggesting that GRK5/6 may be involved in M1 receptor inactivation or signal reprogramming.The relative efficiency of the M1 receptor's interaction with different GRK subtypes determines its preference for downstream signaling pathways.

Objective:To investigate the predictive value of refeeding syndrome (RFS) and its influencing factors for 30-day intensive care unit (ICU) readmission in critically ill patients.Methods:A prospective cohort study was conducted. Critically ill patients admitted to the department of critical care medicine, department of respiratory and critical care medicine, and department of neurology at Tianjin Medical University General Hospital from January to April in 2025 were enrolled. Patients were assessed for RFS according to the American Society for Parenteral and Enteral Nutrition (ASPEN) criteria. General information within 24 hours of ICU admission was collected via the electronic medical record system. Treatment details and 30-day ICU readmission status were dynamically recorded. Participants were divided into readmission and non-readmission groups based on whether ICU readmission occurred within 30 days. Intergroup comparisons were performed to identify differences. Multivariate Logistic regression was used to analyze the relationship between RFS and its influencing factors with 30-day ICU readmission. Receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive performance of risk factors.Results:A total of 196 critically ill patients were enrolled, among whom 25 (12.76%) were readmitted to ICU within 30 days and 171 (87.24%) were not. Significant differences were observed in the readmission group compared with the non-readmission group, including significantly higher rates of nasogastric decompression, higher acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, a higher incidence of RFS, and a longer duration of nasogastric decompression. Multivariate Logistic regression analysis showed that RFS was an independent risk factor for 30-day ICU readmission [odds ratio ( OR) = 5.756, 95% confidence interval (95% CI) was 1.603-20.670, P = 0.007]. APACHEⅡ score showed a positive correlation trend with 30-day ICU readmission ( OR = 1.057, 95% CI was 0.991-1.127, P = 0.092). ROC curve analysis showed that the combined prediction model incorporating RFS and APACHEⅡ score had an area under the ROC curve (AUC) of 0.766 (95% CI was 0.668-0.864), with a sensitivity of 88.0% and a specificity of 62.0%, which was significantly superior to a single indicator (the AUC of RFS and APACHEⅡ score was 0.639 and 0.624, respectively). Conclusions:RFS significantly increases the risk of 30-day ICU readmission in critically ill patients. A combined model incorporating RFS and APACHEⅡ score demonstrates good predictive efficacy for 30-day ICU readmission in critically ill patients.

Objective·To investigate the mechanisms by which different subtypes of G protein-coupled receptor kinases(GRKs)regulate the biased signaling transduction mediated by the muscarinic acetylcholine receptor 1(M1 receptor),focusing on their molecular effects in modulating the binding of the M1 receptor to the downstream heterotrimeric G protein(Gαq-Gβ1-Gγ2)andβ-arrestin 2(βarr2).Methods·By establishing a highly sensitive protein interaction detection system based on bioluminescence resonance energy transfer(BRET),six M1 receptor agonists/allosteric modulators were selected to measure the dynamic interactions between the M1 receptor and four GRK subtypes(GRK2/3/5/6),βarr2,and the G protein under stimulation.All BRET data were statistically quantified using the area under the curve(AUC)of the time-response curves.First,concentration-effect curves were established by treatment with gradient concentrations of agonists/allosteric modulators and AUC fitting,to comprehensively analyze the differences in efficacy between each agonist/allosteric modulator and the endogenous agonist acetylcholine chloride(ACh)in promoting the interactions of M1 receptor with GRK3/5,βarr2,and the G protein;next,GRKs were divided into two groups based on subtypes:GRK2/3 and GRK5/6.The maximum AUC values for the interaction between the M1 receptor and the two GRK groups under high concentrations were calculated respectively,to further evaluate the regulatory propensity of different types of GRKs on the binding strength of the M1 receptor to βarr2 or the G protein.Results·All six agonists/allosteric modulators effectively induced the association of the M1 receptor with GRK3,while simultaneousey inducing dissociation of the M1 receptor from GRK5.The allosteric modulator BQCA not only activated the M1 receptor alone and triggered its binding to downstream signaling proteins,but also,when co-treated with ACh,caused a significant leftward shift of the concentration-effect curves in the M1-G protein and M1-βarr2 systems,suggesting that its potentiation effect on ACh was mainly achieved by reducing the half-maximal effective concentration.A moderate positive correlation was observed between the maximum AUC values of M1-βarr2 and M1-G protein interactions induced by the seven groups of drug treatments(r=0.722,P=0.067).Further analysis showed that the ratio of the maximum AUC for M1-GRK2/3 interaction to that for M1-GRK5/6 interaction was also positively correlated with the ratio of the maximum AUC for M1-βarr2 interaction to that for M1-G protein interaction(r=0.760,P=0.047).Conclusion·The M1 receptor may be pre-coupled with GRK5/6 under basal conditions,and they dissociate upon receptor activation,suggesting that GRK5/6 may be involved in M1 receptor inactivation or signal reprogramming.The relative efficiency of the M1 receptor's interaction with different GRK subtypes determines its preference for downstream signaling pathways.

Objective To explore the value of CT radiomics analysis in predicting the curative effect of extracorporeal shock wave lithotripsy(ESWL)in ureteral calculus(UC)patients.Methods A total of 126 UC patients who underwent ESWL from January 2018 to December 2023 were selected,and randomly divided into training group and validation group at a ratio of 7∶3.Forty-five UC patients from January 2024 to September 2024 were selected as external validation group and divided into two groups according to whether the residual stones were less than 4 mm after operation.There were 81 cases in the successful lithotripsy group and 45 cases in the failed lithotripsy group.The 3D Slicer software was used to outline the stone layer by layer to obtain region of interest(ROI),and 851 radiomics features were extracted.After the observer consistency test,maximum relevance and minimum redundancy(mRMR)algorithm and least absolute shrinkage and selection operator(LASSO),the radiomics features were selected,and the logistic regression model was established.The diagnostic efficiency of the model was analyzed by receiver operating characteristic(ROC)curve.Results The six optimal features were obtained from the radiomics features.The combined clinical-radiomics model showed the best prediction efficiency with area under the curve(AUC)of 0.908,0.906 and 0.908 in the training,validation and external validation groups respectively.Conclusion CT radiomics model can be used to predict the curative effect of UC patients after ESWL,and provide a basis for assisting UC patients in individualized treatment.

Objective To observe conventional color Doppler ultrasound(CDU)and contrast-enhanced ultrasound(CEUS)manifestations of solitary abdominal mass-forming lymphoma.Methods Thirty-two patients with solitary abdominal mass-forming lymphoma confirmed by pathology who underwent CDU examination were retrospectively included,among them 28 patients also received CEUS.CDU manifestations of lesions were observed,including the size,echogenicity,shape,margin,posterior acoustic features,blood flow,as well as presence of cord-like and reticular high echogenicity and vascular encasement or not.The enhancement distribution,degree and pattern of lesion during CEUS were recorded.Results CDU showed that solitary abdominal mass-forming lymphomas lesions mainly appeared as hypoechoic masses with heterogeneous internal echogenicity(24/32,75.00%),irregular shape(28/32,87.50%),clear margin(26/32,81.25%)and posterior acoustic enhancement(28/32,87.50%),with rich blood flow(Adler gradeⅡ—Ⅲ in 24 of 32,75.00%).Vascular encasement and reticular septation were noticed each in 8 cases(8/32,25.00%).During CEUS,peak intensity of contrast agents appeared rapidly in arterial phase,with common high enhancement(26/28,92.86%),which then washed out quickly after the peak or decreased slowly in arterial phase and low enhancement in venous phase.Diffuse distribution(26/28,92.86%),uniform enhancement pattern(20/28,71.43%)and absence of liquefied necrotic area inside(22/28,78.57%)were common findings.Conclusion CDU and CEUS manifestations of solitary abdominal mass-forming lymphoma had characteristics to a certain degree,which might be helpful to early diagnosis.

Objective:To investigate the predictive value of refeeding syndrome (RFS) and its influencing factors for 30-day intensive care unit (ICU) readmission in critically ill patients.Methods:A prospective cohort study was conducted. Critically ill patients admitted to the department of critical care medicine, department of respiratory and critical care medicine, and department of neurology at Tianjin Medical University General Hospital from January to April in 2025 were enrolled. Patients were assessed for RFS according to the American Society for Parenteral and Enteral Nutrition (ASPEN) criteria. General information within 24 hours of ICU admission was collected via the electronic medical record system. Treatment details and 30-day ICU readmission status were dynamically recorded. Participants were divided into readmission and non-readmission groups based on whether ICU readmission occurred within 30 days. Intergroup comparisons were performed to identify differences. Multivariate Logistic regression was used to analyze the relationship between RFS and its influencing factors with 30-day ICU readmission. Receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive performance of risk factors.Results:A total of 196 critically ill patients were enrolled, among whom 25 (12.76%) were readmitted to ICU within 30 days and 171 (87.24%) were not. Significant differences were observed in the readmission group compared with the non-readmission group, including significantly higher rates of nasogastric decompression, higher acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, a higher incidence of RFS, and a longer duration of nasogastric decompression. Multivariate Logistic regression analysis showed that RFS was an independent risk factor for 30-day ICU readmission [odds ratio ( OR) = 5.756, 95% confidence interval (95% CI) was 1.603-20.670, P = 0.007]. APACHEⅡ score showed a positive correlation trend with 30-day ICU readmission ( OR = 1.057, 95% CI was 0.991-1.127, P = 0.092). ROC curve analysis showed that the combined prediction model incorporating RFS and APACHEⅡ score had an area under the ROC curve (AUC) of 0.766 (95% CI was 0.668-0.864), with a sensitivity of 88.0% and a specificity of 62.0%, which was significantly superior to a single indicator (the AUC of RFS and APACHEⅡ score was 0.639 and 0.624, respectively). Conclusions:RFS significantly increases the risk of 30-day ICU readmission in critically ill patients. A combined model incorporating RFS and APACHEⅡ score demonstrates good predictive efficacy for 30-day ICU readmission in critically ill patients.