Objective To investigate the value of ultrasonographic features combined with immunohistochemistry in predicting axillary lymph node metastasis in middle-aged women with breast cancer.Methods A retrospective analysis was conducted on 827 middle-aged female breast cancer patients who underwent surgical treatment at the Affiliated Hospital of Chengde Medical University from June 2017 to June 2023.Ultrasonographic and immunohistochemical information was collected,and the patients were randomly allocated into a training set(579 patients)and a validation set(248 patients).Univariate and multivariate Logistic regression analyses were performed to identify ultrasonographic and immunohistochemical risk factors associated with axillary lymph node metastasis in these patients,and a nomogram model was developed.Receiver operating characteristic curves and calibration curves were established to evaluate the performance of the nomogram model,and clinical decision curves were built to assess the clinical value of the model.Results The maximum diameter,morphology,boundary,calcification,and expression of human epidermal growth facor receptor 2 and Ki-67 in breast cancer lesions were identified as risk factors for predicting axillary lymph node metastasis in middle-aged women.The areas under the curve of the nomogram model on the training and validation sets were 0.747(0.707-0.787)and 0.714(0.647-0.780),respectively.Calibration curves and clinical decision curves indicated good consistency and performance of the model.Conclusion The nomogram model constructed based on ultrasonographic features and immunohistochemistry of the primary breast cancer lesion demonstrates high value in predicting axillary lymph node metastasis in middle-aged women with breast cancer.
Humans ; Female ; Breast Neoplasms/diagnostic imaging* ; Middle Aged ; Lymphatic Metastasis/diagnostic imaging* ; Axilla ; Retrospective Studies ; Nomograms ; Ultrasonography ; Immunohistochemistry ; Lymph Nodes/diagnostic imaging* ; Risk Factors ; Ki-67 Antigen

Objective:To investigate the expression and clinical significance of zinc finger protein Kruppel-like factor 4 (KLF4) and topoisomeraseⅡalpha (TOP2A) in breast cancer.Methods:From Jan. 2022 to Jun. 2023, 126 patients with breast cancer were selected for examination in the clinical Laboratory of the First Affiliated Hospital of Inner Mongolia Medical University. Breast cancer tissues and adjacent tissues of all patients were collected. The expressions of KLF4 and TOP2A were detected by immunohistochemical staining, and the relationship of the expressions of KLF4 and TOP2A with the pathological features of patients was analyzed. Patients were divided into recurrence group and non-recurrence group according to whether they had recurrence after surgery. The expression of KLF4 and TOP2A in the two groups were compared. Spearman correlation analysis was used to analyze the relationship of KLF4 and TOP2A with breast cancer recurrence, and multivariate Cox risk regression was used to analyze the risk factors of breast cancer recurrence after surgery.Results:The positive expression rate of KLF4 in tumor tissues was lower than that in paracancer tissues, and the positive expression rate of TOP2A was higher ( χ 2=35.24, 53.89, P<0.001) ; The levels of KLF4 and TOP2A in tumor tissues were correlated with TNM stage, differentiation degree, borderline state and lymph node metastasis ( χ 2=10.98, 8.49, 4.28, 7.28, P=0.001, 0.004, 0.039, 0.007; χ 2=8.15, 8.78, 6.39, 7.20, P=0.004, 0.003, 0.011, 0.007), and the expression of TOP2A was correlated with the pathological type ( χ 2=4.31, P=0.04) ; The recurrence rate in KLF4 negative expression group and TOP2A positive expression group was higher than that in KLF4 positive expression group and TOP2A negative expression group ( χ 2=4.53, 5.92, P=0.033, 0.015) ; Spearman correlation analysis showed that positive expression of KLF4 was negatively correlated with breast cancer recurrence ( r=-0.43, P<0.001), and positive expression of TOP2A was positively correlated with breast cancer recurrence ( r=0.51, P<0.001) ; Multivariate Cox regression analysis showed that TNM stage, lymph node metastasis, negative KLF4 expression and positive TOP2A expression were independent risk factors for breast cancer recurrence ( P<0.05) . Conclusion:KLF4 is negatively expressed in breast cancer tissues, while TOP2A is positively expressed, and its expression level is closely related to pathological characteristics and has certain evaluation value for postoperative recurrence of breast cancer.

Objective To investigate the risk factors and clinical significance of layered plaques that were detected by optical coherence tomography(OCT)in patients with angiographically intermediate coronary lesions,and relationship with prognosis.Methods This was a signal-center retrospective study focusing on patients whom underwent coronary angiography and OCT.The layered plaque group and non-layered plaque group were divided according to the presence or absence of stratified plaque.Clinical data,laboratory indicators,angiography,and OCT results were collected and compared between the two groups.Using logistic regression to analyze the relationship between stratified plaques and clinical features;Cox regression analysis was used to investigate the influencing factors of cardiovascular adverse events in patients with critical coronary artery disease.Results A total of 172 patients were enrolled,including 96 patients in non-layered plaque group and 76 patients in layered plaque group.Male(OR 2.415,95％CI 1.162-5.020,P=0.018),diabetes(OR 2.505,95％CI 1.137-5.525,P=0.023)and history of hyperlipidemia(OR 3.590,95％CI 1.478-6.333,P=0.003)were independent risk factors for stratified plaque.In OCT analysis,the proportion of thin-cap fibroatheroma(TCFA)plaque,macrophage infiltration,microvascularization,thrombosis,plaque rupture,and intimal dissection,as well as lipid plaque length,lipid plaque arc,and lipid plaque index were higher in the layered plaque group.After adjusting for other risk factors,macrophage infiltration is independently associated with stratified plaques(OR 2.106,95％CI 1.019-4.353,P=0.044).Kaplan-Meier survival analysis showed that the target lesion revascularization rate in the layered plaque group was higher than that in the non-layered plaque group(Log-rank P=0.030).Cox regression analysis shows that it has both stratified plaque and thin fibrous membrane plaque characteristics was an independent predictor of cardiovascular adverse events(HR 5.165,95％CI 1.696-15.727,P=0.004).Conclusions In patients with angiographically intermediate coronary lesions,OCT detection of stratified lesions is often accompanied by other unstable plaque features,indicating an increased risk of adverse cardiovascular events.Simultaneously possessing features of stratified plaques and TCFA is an independent predictor of adverse cardiovascular events in patients with critical coronary artery disease.

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

OBJECTIVE: To investigate the effects of acupuncture on the neurotransmitter levels and gut microbiota in a mouse model of Tourette syndrome (TS). METHODS: Thirty-six male C57/BL6 mice were randomly divided into 4 groups using a random number table method: 3,3'-iminodipropionitrile (IDPN) group, control group, acupuncture group, and tiapride group, with 9 mice in each group. In the IDPN group, acupuncture group, and tiapride group, mice received daily intraperitoneal injections of IDPN (300 mg/kg body weight) for 7 consecutive days to induce stereotyped behaviors. Subsequently, in the acupuncture intervention group, standardized acupuncture treatment was administered for 14 consecutive days to IDPN-induced TS model mice. The selected acupoints included Baihui (DU 20), Yintang (DU 29), Waiguan (SJ 5), and Zulinqi (GB 41). In the tiapride group, mice were administered tiapride (50 mg/kg body weight) via oral gavage daily for 14 consecutive days. The control group, IDPN group, and acupuncture group received the same volume of saline orally for 14 consecutive days. Stereotypic behaviors were quantified through behavioral assessments. Neurotransmitter levels, including dopamine (DA), glutamate (Glu), and aspartate (ASP) in striatal tissue were measured using enzyme-linked immunosorbent assay. Dopamine transporter (DAT) expression levels were additionally quantified through quantitative polymerase chain reaction (qPCR). Gut microbial composition was analyzed through 16S ribosomal RNA gene sequencing, while metabolic profiling was conducted using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Acupuncture administration significantly attenuated stereotypic behaviors, concurrently reducing striatal levels of DA, Glu and ASP concentrations while upregulating DAT expression compared with untreated TS controls (P<0.05 or P<0.01). Comparative analysis identified significant differences in Muribaculaceae (P=0.001), Oscillospiraceae (P=0.049), Desulfovibrionaceae (P=0.001), and Marinifilaceae (P=0.014) following acupuncture intervention. Metabolomic profiling revealed alterations in 7 metabolites and 18 metabolic pathways when compared to the TS mice, which involved various amino acid metabolisms associated with DA, Glu, and ASP. CONCLUSIONS Acupuncture demonstrates significant modulatory effects on both central neurotransmitter systems and gut microbial ecology, thereby highlighting its dual therapeutic potential for TS management through gut-brain axis regulation.
Animals ; Tourette Syndrome/metabolism* ; Gastrointestinal Microbiome ; Neurotransmitter Agents/metabolism* ; Acupuncture Therapy ; Male ; Mice, Inbred C57BL ; Mice

Quality marker (Q-Marker) is an innovative concept and model for quality control of Traditional Chinese medicines (TCMs), which will navigate the new direction of quality development of TCMs. Yet, how to characterize the overall quality attributes of TCMs and their biological effects is still debating. In view of this key scientific issue, this paper proposes a research method based on mass spectrometry imaging (MSI) technology for the discovery and confirmation of TCMs Q-Marker. MSI is powerful in investigating the spatial distribution of molecules in a variety of samples, and visualizing the information obtained from MS. On this basis, combine with the five principles of TCMs Q-Marker validation, i.e., specificity, transmission and traceability, testability, prescription compatibility, and validity, were applied to confirm the finalized Q-Marker. It will lead the new direction of quality development of TCMs.

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

With the rapid development of digital technology, digital twin technology shows great potential for application in the medical and nursing fields. This paper reviews the main elements and key aspects of digital twins, their application scenarios and effects in medicine and nursing, and application challenges faced, with a view to providing innovative solution ideas for healthcare professionals and promoting the application and development of digital twins in medicine and nursing.

Objective To explore the application value of MRI diaphragmatic navigation technology combined with three dimensional liver acquisition with volume acceleration-flexible(3D LAVA-FLEX)sequence in abdominal enhanced imaging of infants and young children.Methods A retrospective analysis was conducted on imaging data of 84 infants and young children who underwent abdominal enhanced MRI examination in our hospital between January 2021 and December 2023.All 84 infants and young children initially underwent conventional dynamic contrast-enhanced 3D LAVA-FLEX sequence scanning;the delayed phase images obtained were included in the dynamic enhancement group.Subsequently,diaphragmatic navigation combined with 3D LAVA-FLEX sequence examination was implemented,and the obtained images were included in the diaphragm navigation group.Subjective scoring was performed for images in both groups,while the signal to noise ratio(SNR),contrast to noise ratio(CNR),and artifact quantification(AQ)were measured and compared between the two groups.Results The respiratory motion artifacts,the clarity of liver parenchyma enhancement,the clarity of liver vascular enhancement,the clarity of spleen parenchyma enhancement and the overall image quality score in the diaphragm navigation group were higher than those in the dynamic enhancement group,and the differences were statistically significant(P<0.05).There were statistically significant differences in SNR and AQ between the two groups of images(P<0.000 1),while there was no statistically significant difference in CNR between the two groups of images(P>0.05).Conclusion Diaphragmatic navigation technology combined with 3D LAVA-FLEX sequence imaging can improve the image quality of abdominal MRI enhanced imaging in infants and young children,and provide a reference for clinical diagnosis and treatment.