Objective:To investigate altered neurovascular coupling in patients with depression(DEP)using resting-state functional magnetic resonance imaging(MRI)and arterial spin labeling perfusion MRI,as well as its association with depressive symptoms.Methods:Neuropsychological assessment and multimodal MRI scans were performed for 25 DEP patients and 35 healthy controls(HCs).Arterial spin labeling perfusion MRI was used to calculate cerebral blood flow(CBF),and functional MRI was used to calculate regional homogeneity(ReHo).The Pearson correlation coefficient between CBF and ReHo was calculated to obtain neurovascular cou-pling.Results:At the whole-brain level,CBF-ReHo coupling was reduced in DEP patients compared with HCs.At the brain region level,CBF-ReHo coupling was reduced in 26 brain regions in DEP patients,which were mainly located in the visual network,the default network,and the auditory network.The correlation analysis showed that the coupling values of the left suboccipital gyrus,the left angular gyrus,and the left thalamus were negatively correlated with Hamilton Depression Scale score.Conclusion:There is a sig-nificant reduction in neurovascular coupling in DEP patients,which is correlated with the severity of DEP.

Objective To study the latent classification of medical service utilization behaviors among middle-aged and older chronic disease patients,providing a theoretical basis for the allocation of medical resources.Methods Using data from the 2018 China Health and Retirement Longitudinal Study(CHARLS)database,latent class analysis was employed to conduct subgroup analysis on the medical choice preferences of middle-aged and older chronic disease patients.Logistic regression was used to analyze the influence of various factors on medical preference subgroups.Results The medical choice preferences of middle-aged and older chronic disease patients were classified into three latent subgroups:public hospital treatment preference type,non-public hospital treatment preference type,and public hospital consultation preference type.Compared to the public hospital treatment preference type,patients under 60 years old(OR=0.456,P=0.034),those living in rural areas(OR=0.256,P=0.006),and those with smoking habits(OR=3.11,P＜0.001)were more inclined to choose non-public hospitals for treatment.In contrast,patients over 60 years old(OR=1.916,P=0.015),those with an education level of primary school or above(OR=2.595,P=0.004),and those with smoking habits(OR=2.591,P=0.044)tended to choose public hospitals for consultation or physical examinations.Conclusion Currently,private hospitals play an increasingly prominent role in chronic disease treatment.However,the utilization rate of traditional Chinese medicine among middle-aged and older chronic disease pa-tients is relatively low,and health awareness remains weak.It is recommended to strengthen the regulation of private hospitals,enhance the credibility and accessibility of traditional Chinese medicine,and intensify health education in communities to meet the growing health demands of middle-aged and older chronic disease patients.

Objective To analyze the characteristics of TCM symptoms of aging in female insomnia patients;To provide syndrome differentiation evidence for clinical prevention and treatment of female aging.Methods A cross-sectional study method was used to include female insomnia patients who attended outpatient clinics at Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing Changping District Hospital of Traditional Chinese Medicine,and the Third Affiliated Hospital of Beijing University of Chinese Medicine from August 2021 to July 2024.The patients'clinical information was collected,and frequency analysis,factor analysis,and clustering analysis of the relevant clinical information of the 107 female insomnia patients were conducted,which,together with the experts'opinions,resulted in characteristics of TCM syndrome elements and syndrome distribution of aging in female insomnia patients.Results Totally 20 core items were screened and 7 common factors were obtained from the factor analysis.There were 5 types of syndrome elements of disease location associated with aging symptoms in female patients with insomnia,including heart,liver,spleen,kidney and lung;and there were 7 types of syndrome elements of disease property,including qi deficiency,yin deficiency,qi stagnation,blood deficiency,heat,phlegm,and dampness.There were 4 types of syndromes were obtained from the systematic clustering,including heart-kidney disharmony syndrome,heart-liver stagnation syndrome,spleen deficiency and qi stagnation syndrome,lung-spleen qi deficiency syndrome.Conclusion By analyzing the TCM syndrome characteristics of aging symptoms in female patients with insomnia,four types of syndromes are obtained.The heart-kidney disharmony syndrome is the common syndrome.The internal relationship between insomnia and aging process in female patients with insomnia is revealed from the perspective of pathogenesis,which can provide a research basis for the clinical practice of TCM anti-aging guided by syndrome differentiation and treatment in the future.

Objective To study the latent classification of medical service utilization behaviors among middle-aged and older chronic disease patients,providing a theoretical basis for the allocation of medical resources.Methods Using data from the 2018 China Health and Retirement Longitudinal Study(CHARLS)database,latent class analysis was employed to conduct subgroup analysis on the medical choice preferences of middle-aged and older chronic disease patients.Logistic regression was used to analyze the influence of various factors on medical preference subgroups.Results The medical choice preferences of middle-aged and older chronic disease patients were classified into three latent subgroups:public hospital treatment preference type,non-public hospital treatment preference type,and public hospital consultation preference type.Compared to the public hospital treatment preference type,patients under 60 years old(OR=0.456,P=0.034),those living in rural areas(OR=0.256,P=0.006),and those with smoking habits(OR=3.11,P＜0.001)were more inclined to choose non-public hospitals for treatment.In contrast,patients over 60 years old(OR=1.916,P=0.015),those with an education level of primary school or above(OR=2.595,P=0.004),and those with smoking habits(OR=2.591,P=0.044)tended to choose public hospitals for consultation or physical examinations.Conclusion Currently,private hospitals play an increasingly prominent role in chronic disease treatment.However,the utilization rate of traditional Chinese medicine among middle-aged and older chronic disease pa-tients is relatively low,and health awareness remains weak.It is recommended to strengthen the regulation of private hospitals,enhance the credibility and accessibility of traditional Chinese medicine,and intensify health education in communities to meet the growing health demands of middle-aged and older chronic disease patients.

Objective To analyze the characteristics of TCM symptoms of aging in female insomnia patients;To provide syndrome differentiation evidence for clinical prevention and treatment of female aging.Methods A cross-sectional study method was used to include female insomnia patients who attended outpatient clinics at Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing Changping District Hospital of Traditional Chinese Medicine,and the Third Affiliated Hospital of Beijing University of Chinese Medicine from August 2021 to July 2024.The patients'clinical information was collected,and frequency analysis,factor analysis,and clustering analysis of the relevant clinical information of the 107 female insomnia patients were conducted,which,together with the experts'opinions,resulted in characteristics of TCM syndrome elements and syndrome distribution of aging in female insomnia patients.Results Totally 20 core items were screened and 7 common factors were obtained from the factor analysis.There were 5 types of syndrome elements of disease location associated with aging symptoms in female patients with insomnia,including heart,liver,spleen,kidney and lung;and there were 7 types of syndrome elements of disease property,including qi deficiency,yin deficiency,qi stagnation,blood deficiency,heat,phlegm,and dampness.There were 4 types of syndromes were obtained from the systematic clustering,including heart-kidney disharmony syndrome,heart-liver stagnation syndrome,spleen deficiency and qi stagnation syndrome,lung-spleen qi deficiency syndrome.Conclusion By analyzing the TCM syndrome characteristics of aging symptoms in female patients with insomnia,four types of syndromes are obtained.The heart-kidney disharmony syndrome is the common syndrome.The internal relationship between insomnia and aging process in female patients with insomnia is revealed from the perspective of pathogenesis,which can provide a research basis for the clinical practice of TCM anti-aging guided by syndrome differentiation and treatment in the future.

Objective: To evaluate the immune function of epitope peptides interacting with porcine PD-1 or PD-L1. Methods: We optimized and synthesized peptides (PD-L14QN-GF and PD-L14QN-AF) using the solid-phase method and assessed their effects on peripheral blood mononuclear cell (PBMC) proliferation and PD-1 and cytokine expression after porcine reproductive and respiratory syndrome virus (PRRSV) infection in vitro and on antibody responses to a porcine circovirus type 2 (PCV2) vaccine in vivo. Results: The optimized peptides PD-L14QN-GF and PD-L14QN-AF exhibited lower binding free energy and higher stability when interacting with the PD-1 target protein.Under both PRRSV-infected and non-infected conditions in vitro, both peptides enhanced the proliferation of PBMCs, inhibited PRRSV RNA replication, and downregulated PD-1 transcription levels. Additionally, PD-L14QN-GF and PD-L14QN-AF upregulated the mRNA transcription and protein secretion of interleukin (IL)-2, IL-10, and interferon-γ to varying degrees. In vivo experiments demonstrated that PD-L14QN-GF significantly increased the antibody titer and seroconversion rate of the PCV2 vaccine. Conclusions and Relevance: PD-L14QN-GF and PD-L14QN-AF induced stronger immune responses than PD-L14. PD-L14QN-GF has potential as an immune-enhancing adjuvant.

Objective To investigate the value of magnetic resonance image-diffusion weighted imaging(MRI-DMI)combined with attenuation imaging(ATI)in the diagnosis of focal nodular lesions<2 cm in the back-ground of fatty liver.Methods The clinical data of 68 patients with fatty liver complicated with focal nodular lesions<2 cm were retrospectively analyzed from June 2022 to June 2023 in Huaihe Hospital of Henan University.All patients underwent MRI,pathology and ATI examination.According to the degree of fatty liver disease,68 patients were divided into severe group(n=24),moderate group(n=27)and mild group(n=17).The apparent diffusion coefficient(ADC)and acoustic attenuation coefficient(AC)values of patients with different focal lesions were compared with clinical data,and the ADC values and AC values of patients with different fatty liver lesions were compared with clinical data,and the correlation was analyzed by Pearson.To analyze the value of MRI-DWI combined with AC value in the diagnosis of malignant fatty liver disease with focal nodular disease<2 cm.Results Pathological diagnosis showed that 41 of the 68 patients were benign and 27 were malignant.There were no significant differences in low density lipoprotein cholesterol(LDL-C),age,triglyceride(TG),sex,total cholesterol(TC)and high density lipoprotein cholesterol(HDL-C)between benign nodule group and malignant nodule group(P>0.05).There was no difference in TG,age,HDL-C,sex,TC and LDL-C among mild,moderate and severe groups(P>0.05).The ADC value of malignant nodule group was lower than benign nodule group under different b values(P<0.05),and the AC value of malignant nodule group was higher than that of benign nodule group(P<0.05).ADC value under different b values in the severe group was lower than mild and moderate groups(P<0.05),ADC value under different b values in the moderate group was lower than mild group(P<0.05),AC value in the severe group was higher than mild and moderate groups(P<0.05),and AC value in the moderate group was higher than mild group(P<0.05).ADC values at different b values were negatively correlated with the degree of fatty liver disease(P<0.05),but not with TG,HDL-C,TC and LDL-C(P>0.05).AC was positively correlated with the degree of fatty liver disease(P<0.05),negatively correlated with HDL-C(P<0.05),but not with TG,TC and LDL-C(P>0.05).The area under the curve(AUC)values of MRI-DWI,AC and their combi-nation in the diagnosis of fatty liver complicated with focal nodule disease<2 cm into malignancy were 0.775,0.773 and 0.909,respectively(P<0.05),and the AUC value of the combination was higher(P<0.05).Conclusion MRI-DWI and ATI have important value in the differential diagnosis of benign and malignant lesions of focal nodular lesions<2 cm in the background of fatty liver,and the combination of MRI-DWI and ATI has higher diagnostic value.

This study explores the potential antiepileptic mechanism of ursolic acid(UA)and its improvement of GABAergic interneuron damage induced by epilepsy based on transcriptome analysis.Hippocampal tissues from rats in the control group(NC group),epilepsy group(SE group),and epilepsy UA treatment group(UA group)were subjected to full-length transcriptome sequencing.The obtained sequencing data were analyzed,using gene ontology(GO),the Kyoto Encyclopedia of Genes and Genomes(KEGG),and protein-protein interaction(PPI)to perform the analysis of differential genes(DEGs).The expression levels of key differential genes were verified using RT-qPCR in hippocampal tissue.Finally,an epilepsy in vitro model was constructed on primary neurons,RT-qPCR was used to verify the expression levels of key differential genes,and the expression level of GABAA receptor γ2 subunit(GABRG2)on neurons was further examined using immunofluorescence and Western blot.The heatmap of pairwise sample expression correlation and the clustering analysis of differentially expressed genes showed that the SE group was farthest from the NC group,and that after UA treatment,the overall trend shifted towards the normal group.Compared with the SE group,a total of 220 differential genes were screened in the UA group,including 143 upregulated genes and 77 downregulated genes.GO enrichment analysis showed that it involved three processes in the primary classification:biological processes,cellular components,and molecular functions.KEGG pathway enrichment analysis showed that DEGs were involved in 36 biological pathways,including cAMP signaling pathway and calcium signaling pathway.PPI analysis showed that DEGs were closely related to GABA and inflammation.RT-qPCR results showed that UA treatment increased the expression levels of GABA receptor-related gene(Gng4),GABA synthesis-related gene(Camk2a,Vgf,and Npy)and inflammation-related gene(Timp1 and Spp1)in hippocampal tissue,and decreased the expression levels of GABA synthesis-related gene(Nptx2)and cAMP-related pathway gene(Gnas).It further confirmed that UA treatment increased the expression levels of Gng4 and Camk2a on neurons and decreased the expression level of Gnas.Immunofluorescence and Western blot results showed that,compared with the SE group,the expression level of GABRG2 on primary neurons increased after UA treatment.This study enriched the transcriptome data of UA's antiepileptic effect and laid a theoretical foundation for further research on UA's antiepileptic and neuroprotective effects.

MEK is a canonical effector of mutant KRAS; however, MEK inhibitors fail to yield satisfactory clinical outcomes in KRAS-mutant cancers. Here, we identified mitochondrial oxidative phosphorylation (OXPHOS) induction as a profound metabolic alteration to confer KRAS-mutant non-small cell lung cancer (NSCLC) resistance to the clinical MEK inhibitor trametinib. Metabolic flux analysis demonstrated that pyruvate metabolism and fatty acid oxidation were markedly enhanced and coordinately powered the OXPHOS system in resistant cells after trametinib treatment, satisfying their energy demand and protecting them from apoptosis. As molecular events in this process, the pyruvate dehydrogenase complex (PDHc) and carnitine palmitoyl transferase IA (CPTIA), two rate-limiting enzymes that control the metabolic flux of pyruvate and palmitic acid to mitochondrial respiration were activated through phosphorylation and transcriptional regulation. Importantly, the co-administration of trametinib and IACS-010759, a clinical mitochondrial complex I inhibitor that blocks OXPHOS, significantly impeded tumor growth and prolonged mouse survival. Overall, our findings reveal that MEK inhibitor therapy creates a metabolic vulnerability in the mitochondria and further develop an effective combinatorial strategy to circumvent MEK inhibitors resistance in KRAS-driven NSCLC.

Objective:Using ultrasound imaging technology to evaluate the contraction characteristics of diaphragm in patients with chronic low back pain.Methods:Twenty nine patients with chronic low back pain and 26 healthy persons recruited from the rehabilitation department of the Third Affiliated Hospital of Sun Yat-sen University from November 2019 to April 2020 were selected and divided into the low back pain (LBP) group and the healthy control group. The thickness of the diaphragm (Tdi) of the subjects during deep breathing was evaluated by portable color Doppler ultrasound equipment under different body positions. The subjects were required to perform maximum inspiration for total lung capacity (TLC) and expiration for functional residual capacity (FRC) in the supine and standing position, respectively. The end-inspiratory diaphragm thickness (TdiTLC) and end-expiratory diaphragm thickness (TdiFRC) were recorded, and the diaphragmatic thickening fraction (DTF) was calculated. The general data of subjects with lower back pain and the correlation between Oswestry Dysfunction Index (ODI) and diaphragm function were analyzed; The diaphragm function of healthy control group and LBP group were compared; The receiver operating characteristic (ROC) curve of Tdi and DTF in the diagnosis of lower back pain were analyzed.Results:ODI lifting score was negatively correlated with standing TdiTLC ( r=-0.50, P<0.01). In intra-group comparison, the TdiTLC and TdiFRC values of healthy subjects in standing position were increased compared with those in supine position ( t=6.115, 7.314, all P<0.001); In standing position, TdiTCL and TdiFRC values in LBP group were increased compared with those in supine position ( t=2.834, 4.673, all P<0.01). In comparison between groups, TdiTLC values in supine and standing position of LBP group were significantly lower than those in healthy control group ( t=2.597, 3.338, all P<0.05); In standing position, TdiFRC of patients in LBP group was significantly lower than that of healthy control group ( t=2.098, P=0.041) and DTF value of patients in LBP group was significantly lower than that of healthy control group ( t=2.902, P=0.006). When TdiTCL≤3.3 mm in supine position was used to predict low back pain, the diagnostic sensitivity and specificity were 78.6% and 53.8%, respectively, and the area under the curve was 0.661. When TdiTCL≤4.5 mm in standing position was used to predict low back pain, the diagnostic sensitivity and specificity were 95.7% and 46.2%, respectively, and the area under the curve was 0.759. When DTF≤81.3% in standing position was used to predict low back pain, the diagnostic sensitivity and specificity were 52.2% and 84.6%, respectively, and the area under the curve was 0.698. Conclusions:It is found in our study that the diaphragm contractile function of patients with lower back pain is worse than that of normal subjects, and the difference was significant in standing position. We suggest that the right-side ultrasound image acquisition in the patient′s standing position is helpful to ensure the accuracy and objectivity of the measurement results. TdiTCL≤4.5 mm or DTF≤81.3% in standing position can be used as one of the reference indexes for the combined diagnosis of chronic low back pain.