Objective To observe the effect of Kaixin Powder on neuroinflammation in APP/PS1 mice by regulating WDFY1/TLR4/NF-κB signaling pathway;To explore its mechanism of intervening in Alzheimer disease(AD).Methods APP/PS1 transgenic mice were randomly divided into model group,donepezil hydrochloride group(0.66 mg/kg),and Kaixin Powder low-,medium-and high-dosage groups(1.625,3.25,6.5 g/kg),C57BL/6J mice were set as blank control group,with 8 mice in each group,and corresponding drug intervention was given to medicaction group for 24 weeks.Morris water maze,Y maze and novel object recognition experiments were conducted to assess the cognitive function and learning and memory abilities of mice,immunohistochemical staining was used to detect the deposition of β-amyloid protein(Aβ)in hippocampus,the morphology and Nissl bodies of hippocampal CA1 neurons were observed using HE staining and Nissl staining,ELISA was used to detect the serum contents of interleukin(IL)-6,IL-17,IL-1β and tumor necrosis factor-α(TNF-α),Western blot was used to detect the protein expression of calcium-binding adapter molecule 1(Iba1),glial fibrillary acidic protein(GFAP),WDFY1,Toll like receptor 4(TLR4),Toll like receptor associated molecule(TRAM),TIR domain adapter protein(TRIF),NF-κB p65 and p-NF-κB p65 in hippocampal tissue,RT-qPCR was used to detect the mRNA expression of WDFY1,TLR4,TRAM,TRIF and NF-κB p65 in hippocampal tissue.Results Compared with the blank control group,the model group had significantly prolonged escape latency,reduced platform crossings,decreased autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),with increased deposition of Aβ in hippocampal tissue(P<0.01),damaged morphological structure of neurons,reduced number of neurons and Nissl bodies,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly increased,the expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 protein and WDFY1,TLR4,TRAM,TRIF mRNA in hippocampal tissue significantly increased(P<0.01).Compared with the model group,Kaixin Powder groups and donepezil hydrochloride group had significantly shortened escape latency and increased platform crossings,autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),hippocampal Aβ deposition reduced in Kaixin Powder medium-,high-dosage groups and donepezil hydrochloride group,the morphological structure of neurons recovered,the number of neurons and Nissl bodies increased,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly decreased(P<0.05,P<0.01),and the protein expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 and the mRNA expressions of WDFY1,TLR4,TRAM and TRIF in hippocampal tissue significantly decreased(P<0.05,P<0.01).Conclusion Kaixin Powder can improve cognitive function and learning and memory abilities in AD model mice,alleviate hippocampal neuron damage and Aβ deposition,inhibit the activation of microglia and astrocytes,and thereby reduce serum inflammatory cytokine release.Its mechanism may be related to regulating the WDFY1/TLR4/NF-κB signaling pathway to inhibit neuroinflammation.

ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

Five previously undescribed diterpenoids, named succipenoids D‒H (1‒5), along with four undescribed lignans, named succignans A‒D (6‒9), were isolated from the dichloromethane extract of Chinese medicinal succinum. Compounds 1‒5 were characterized as nor-abietane diterpenoids, while compounds 6‒9 were identified as lignans polymerized from two groups of phenylpropanoid units. The structures of these novel compounds, including their absolute configurations, were determined through spectroscopic and computational methods. Biological assessments of renal fibrosis demonstrated that compounds 6 and 7 effectively reduce the expression of proteins associated with renal fibrosis, including α-smooth muscle actin (α-SMA), collagen I, and fibronectin in transforming growth factor-β1 (TGF-β1) induced normal rat kidney proximal tubular epithelial cells (NRK-52e).
Animals ; Rats ; Lignans/isolation & purification* ; Diterpenes/isolation & purification* ; Fibrosis/drug therapy* ; Drugs, Chinese Herbal/pharmacology* ; Molecular Structure ; Cell Line ; Kidney Diseases/pathology* ; Transforming Growth Factor beta1/genetics* ; Kidney/metabolism* ; Actins/genetics* ; Fibronectins/genetics* ; Collagen Type I/genetics* ; Epithelial Cells/metabolism*

Objective:To discuss the relationship between the systolic blood pressure (SBP) circadian rhythm and blood pressure variability (BPV) and the left ventricular ejection fraction (LVEF) among 178 patients with hypertension.Methods:This article was a retrospective study. Totally 178 patients with hypertension from January 2020 to January 2022 were selected based on incorporated basis. 24-hour dynamic blood pressure monitoring and echocardiography examination were performed. Data such as patients' SBP circadian rhythm, BPV, heart ultrasound heart dynamic maps were collected, and the relationship between SBP circadian rhythm and BPV and their LVEF was explored.Results:Among the 178 patients, the decreased proportion of SBP circadian rhythm>the proportion of existed SBP circadian rhythm>the proportion of inverted SBP circadian rhythm>the proportion of disappearance of SBP circadian rhythm; patients with disappearance of SBP circadian rhythm were the youngest (63.8 ± 14.5) years old, and patients with inverted SBP circadian rhythm were the oldest (71.5 ± 9.4) years old ( P<0.05); the 24-hour systolic blood pressure standard deviation of SBP circadian rhythm was observed in patients with (13.1 ± 2.8) mmHg

Objective:To evaluate the performance of the neural network model in segmenting gout tophus in the first metatarsophalangeal（MTP1）joint ultrasound images.Methods:A total of 1 218 tophus images from 381 patients who underwent MTP1 ultrasound examinations in the Affiliated Hospital of Qingdao University between May 2023 and December 2024 were prospectively collected. The images were divided into training，validation，and test sets in a ratio of 7∶2∶1. Multiple neural network models were trained to automatically identify and segment tophus in the images，with physician-annotated tophus regions serving as the reference standard. Model performance was evaluated in the test set，and the impact of tophus characteristics（e.g.，echogenicity，size，and presence of bone erosion）on segmentation efficacy was analyzed.Results:In the test set，CMUNeXt demonstrated superior tophus segmentation performance versus Unet，Unet++，TransUnet，and CMU-Net，achieving an accuracy of 99.1%，precision of 79.1%，recall of 84.6%，intersection over union of 68.8%，and Dice similarity coefficient of 80.2%. Logistic regression identified tophus echogenicity，size，and bone erosion as independent efficacy factors OR（95% CI）=7.275（1.598-33.129），21.303（4.282-105.985），13.520（3.617-50.530），0.076（0.007-0.823）（all P<0.05）. Hypoechoic tophus demonstrated significantly superior segmentation performance compared to mixed-echoic and isoechoic tophus（all P<0.05），and lesions with larger maximum diameters（>10 mm）were segmented more effectively than smaller tophus（ P<0.05）. Conclusions:The CMUNeXt model enables accurate identification and segmentation of tophus in MTP1 ultrasound images，particularly excelling for larger and hypoechoic lesions. This approach holds significant promise for AI-assisted diagnosis of MTP1 gouty arthritis.

Objective To observe the effect of Kaixin Powder on neuroinflammation in APP/PS1 mice by regulating WDFY1/TLR4/NF-κB signaling pathway;To explore its mechanism of intervening in Alzheimer disease(AD).Methods APP/PS1 transgenic mice were randomly divided into model group,donepezil hydrochloride group(0.66 mg/kg),and Kaixin Powder low-,medium-and high-dosage groups(1.625,3.25,6.5 g/kg),C57BL/6J mice were set as blank control group,with 8 mice in each group,and corresponding drug intervention was given to medicaction group for 24 weeks.Morris water maze,Y maze and novel object recognition experiments were conducted to assess the cognitive function and learning and memory abilities of mice,immunohistochemical staining was used to detect the deposition of β-amyloid protein(Aβ)in hippocampus,the morphology and Nissl bodies of hippocampal CA1 neurons were observed using HE staining and Nissl staining,ELISA was used to detect the serum contents of interleukin(IL)-6,IL-17,IL-1β and tumor necrosis factor-α(TNF-α),Western blot was used to detect the protein expression of calcium-binding adapter molecule 1(Iba1),glial fibrillary acidic protein(GFAP),WDFY1,Toll like receptor 4(TLR4),Toll like receptor associated molecule(TRAM),TIR domain adapter protein(TRIF),NF-κB p65 and p-NF-κB p65 in hippocampal tissue,RT-qPCR was used to detect the mRNA expression of WDFY1,TLR4,TRAM,TRIF and NF-κB p65 in hippocampal tissue.Results Compared with the blank control group,the model group had significantly prolonged escape latency,reduced platform crossings,decreased autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),with increased deposition of Aβ in hippocampal tissue(P<0.01),damaged morphological structure of neurons,reduced number of neurons and Nissl bodies,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly increased,the expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 protein and WDFY1,TLR4,TRAM,TRIF mRNA in hippocampal tissue significantly increased(P<0.01).Compared with the model group,Kaixin Powder groups and donepezil hydrochloride group had significantly shortened escape latency and increased platform crossings,autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),hippocampal Aβ deposition reduced in Kaixin Powder medium-,high-dosage groups and donepezil hydrochloride group,the morphological structure of neurons recovered,the number of neurons and Nissl bodies increased,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly decreased(P<0.05,P<0.01),and the protein expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 and the mRNA expressions of WDFY1,TLR4,TRAM and TRIF in hippocampal tissue significantly decreased(P<0.05,P<0.01).Conclusion Kaixin Powder can improve cognitive function and learning and memory abilities in AD model mice,alleviate hippocampal neuron damage and Aβ deposition,inhibit the activation of microglia and astrocytes,and thereby reduce serum inflammatory cytokine release.Its mechanism may be related to regulating the WDFY1/TLR4/NF-κB signaling pathway to inhibit neuroinflammation.

Objective:To analyze the risk factors for atrial high-rate episodes (AHRE) following cardiac resynchronization therapy (CRT) and construct a predictive model for the occurrence of AHRE.Methods:This was a case-control study. Patients who received CRT treatment for heart failure in the Second Affiliated Hospital of Second Affiliated Hospital of Army Military Medical University from January 2017 to December 2020 were selected and divided into AHRE group and non-AHRE group according to whether AHRE occurred during the follow-up period. Baseline clinical data were collected. Patients were followed up regularly after CRT or cardiac resynchronization therapy defibrillator (CRT-D) implantation until August 31, 2022. Logistic regression model was used to analyze the factors influencing the occurrence of AHRE in patients with heart failure treated with CRT, and a nomogram prediction model was established. The receiver operating characteristic (ROC) curve was used to evaluate the nomogram model, and the Hosmer-Lemeshow test was used to evaluate the consistency of the prediction model.Results:A total of 198 patients, aged (62±8) years, 138 (69.7%) males, were enrolled, of whom 52 (26.3%) patients developed AHRE (AHRE group) and 146 (73.7%) had no AHRE (non-AHRE group) during the follow-up period. Multivariate logistic regression analysis revealed that age, coronary heart disease, C-reactive protein, left atrial volume, and left ventricular ejection fraction (LVEF) were independent influencing factors of heart failure patients developing AHRE after CRT surgery (all P<0.05). A nomogram prediction model was constructed by combining 5 indicators: age, coronary heart disease, C-reactive protein, left atrial volume, and LVEF. In this model, a score of 4 was assigned for age ≥65 years, 4 for coronary heart disease, 4 for C-reactive protein ≥10 ng/ml, 20 for left atrial volume ≥35 ml, and 5 for LVEF ≤30%. The total score was obtained by accumulating the scores of each indicator, and the probability of heart failure patients developing AHRE after CRT surgery was predicted based on the total score. The area under the curve of the nomogram prediction model constructed in this study for predicting AHRE in heart failure patients after CRT surgery was 0.830 (95% CI: 0.795-0.866). The incidence of AHRE predicted by the model was basically consistent with the actual incidence of AHRE. The Hosmer-Lemeshow test indicated a good calibration of the model ( χ2=6.32, P=0.612). Conclusions:Age, coronary heart disease, C-reactive protein, left atrial volume, and LVEF are all independent risk factors for AHRE after CRT treatment. The nomogram prediction model based on the above factors can effectively predict the risk of AHRE in patients with heart failure after CRT, and the ROC curve and consistency test both show good prediction efficiency and consistency.

Objective:To analyze the risk factors for atrial high-rate episodes (AHRE) following cardiac resynchronization therapy (CRT) and construct a predictive model for the occurrence of AHRE.Methods:This was a case-control study. Patients who received CRT treatment for heart failure in the Second Affiliated Hospital of Second Affiliated Hospital of Army Military Medical University from January 2017 to December 2020 were selected and divided into AHRE group and non-AHRE group according to whether AHRE occurred during the follow-up period. Baseline clinical data were collected. Patients were followed up regularly after CRT or cardiac resynchronization therapy defibrillator (CRT-D) implantation until August 31, 2022. Logistic regression model was used to analyze the factors influencing the occurrence of AHRE in patients with heart failure treated with CRT, and a nomogram prediction model was established. The receiver operating characteristic (ROC) curve was used to evaluate the nomogram model, and the Hosmer-Lemeshow test was used to evaluate the consistency of the prediction model.Results:A total of 198 patients, aged (62±8) years, 138 (69.7%) males, were enrolled, of whom 52 (26.3%) patients developed AHRE (AHRE group) and 146 (73.7%) had no AHRE (non-AHRE group) during the follow-up period. Multivariate logistic regression analysis revealed that age, coronary heart disease, C-reactive protein, left atrial volume, and left ventricular ejection fraction (LVEF) were independent influencing factors of heart failure patients developing AHRE after CRT surgery (all P<0.05). A nomogram prediction model was constructed by combining 5 indicators: age, coronary heart disease, C-reactive protein, left atrial volume, and LVEF. In this model, a score of 4 was assigned for age ≥65 years, 4 for coronary heart disease, 4 for C-reactive protein ≥10 ng/ml, 20 for left atrial volume ≥35 ml, and 5 for LVEF ≤30%. The total score was obtained by accumulating the scores of each indicator, and the probability of heart failure patients developing AHRE after CRT surgery was predicted based on the total score. The area under the curve of the nomogram prediction model constructed in this study for predicting AHRE in heart failure patients after CRT surgery was 0.830 (95% CI: 0.795-0.866). The incidence of AHRE predicted by the model was basically consistent with the actual incidence of AHRE. The Hosmer-Lemeshow test indicated a good calibration of the model ( χ2=6.32, P=0.612). Conclusions:Age, coronary heart disease, C-reactive protein, left atrial volume, and LVEF are all independent risk factors for AHRE after CRT treatment. The nomogram prediction model based on the above factors can effectively predict the risk of AHRE in patients with heart failure after CRT, and the ROC curve and consistency test both show good prediction efficiency and consistency.

Objective:To evaluate the performance of the neural network model in segmenting gout tophus in the first metatarsophalangeal（MTP1）joint ultrasound images.Methods:A total of 1 218 tophus images from 381 patients who underwent MTP1 ultrasound examinations in the Affiliated Hospital of Qingdao University between May 2023 and December 2024 were prospectively collected. The images were divided into training，validation，and test sets in a ratio of 7∶2∶1. Multiple neural network models were trained to automatically identify and segment tophus in the images，with physician-annotated tophus regions serving as the reference standard. Model performance was evaluated in the test set，and the impact of tophus characteristics（e.g.，echogenicity，size，and presence of bone erosion）on segmentation efficacy was analyzed.Results:In the test set，CMUNeXt demonstrated superior tophus segmentation performance versus Unet，Unet++，TransUnet，and CMU-Net，achieving an accuracy of 99.1%，precision of 79.1%，recall of 84.6%，intersection over union of 68.8%，and Dice similarity coefficient of 80.2%. Logistic regression identified tophus echogenicity，size，and bone erosion as independent efficacy factors OR（95% CI）=7.275（1.598-33.129），21.303（4.282-105.985），13.520（3.617-50.530），0.076（0.007-0.823）（all P<0.05）. Hypoechoic tophus demonstrated significantly superior segmentation performance compared to mixed-echoic and isoechoic tophus（all P<0.05），and lesions with larger maximum diameters（>10 mm）were segmented more effectively than smaller tophus（ P<0.05）. Conclusions:The CMUNeXt model enables accurate identification and segmentation of tophus in MTP1 ultrasound images，particularly excelling for larger and hypoechoic lesions. This approach holds significant promise for AI-assisted diagnosis of MTP1 gouty arthritis.

Objective The objective of this study was to explore the values of hsa-let-7b-5p in the clinical diagnosis and targeted therapy of non-small cell lung cancer(NSCLC).Methods Thirteen pairs of NSCLC tissues and their adjacent tissues with the same pathological type in Harbin Medical University Cancer Hospital from September to October 2020 were collected,and differen-tially expressed miRNAs were obtained by RNA-Seq,and the expression of candidate miRNAs were verified in NSCLC tissues and cells through qRT-PCR.The effects of miRNAs on the proliferation,migration and invasion ability of NSCLC were verified by CCK-8 assay,clone formation assay,scratch assay and Transwell assay.Target genes were predicted using MiRDB,TarBase and ENCORI da-tabases,and gene enrichment analysis was performed using FunRich tool.Results Compared with adjacent tissues and human bron-chial epithelial cells(HBE),hsa-let-7b-5p was downregulated in NSCLC tissues and cell lines(A549 cells,H1299 cells,H358 cells and H460 cells)(P<0.05).The high expression of hsa-let-7b-5p inhibited the proliferation,migration and invasion ability of NSCLC(P<0.01).The results of target genes and enrichment analysis showed that among 378 target genes and related genes of hsa-let-7b-5p,147 genes were negatively correlated with the expression of hsa-let-7b-5p(P<0.05).Conclusion Hsa-let-7b-5phas inhibitory effects on the proliferation,migration and invasion of NSCLC.