ObjectiveThe frequency difference limen (FDL) serves as a fundamental metric utilized for effectively quantifying the precise perceptual capabilities of the central auditory system. However, traditional measurement methods rely heavily on the active behavioral responses of subjects and are consequently highly susceptible to the negative influence of confounding subjective factors. Furthermore, existing research paradigms frequently employ uniform stimulus configurations that overlook critical individual perceptual differences. Based on brain-computer interface (BCI) technology, this comprehensive study aims to establish an objective and quantitative evaluation method for auditory frequency discrimination by systematically analyzing and decoding the specific neural responses elicited at the exact threshold state. MethodsWe designed a personalized rapid serial auditory presentation (RSAP) paradigm customized based on each individual’s precise FDL. A cohort of eleven healthy participants was recruited to evaluate the paradigm using pure-tone sequences at a baseline frequency of 4 000 Hz. This experimental paradigm simulates a realistic auditory perception environment through the continuous presentation of acoustic stimuli, thereby allowing for an in-depth investigation into the specific neural representations evoked by weak frequency deviations at the threshold state. Given that auditory stimulus-evoked response features exhibit complex and differentiated spatiotemporal distribution patterns across multiple frequency domains, this study further deeply integrates the cross-scale feature interaction module with the dynamic spatiotemporal attention allocation strategy, innovatively proposing the Multi-Scale Spatial-Temporal Dual Attention Network (MS-STAMNet). Specifically, the network constructs parallel processing branches with multiple receptive fields and introduces a dynamic adaptive weighting strategy to precisely localize core neural activity signals, further deeply integrating multi-scale information through cross-branch feature information interaction to achieve robust single-trial decoding of weak auditory evoked responses. ResultsThe comprehensive electrophysiological data analysis demonstrated that subtle auditory frequency deviation stimuli presented at the threshold level successfully elicited pronounced N2 and P3 event-related potential features, reflecting pre-attentive mismatch detection and subsequent cognitive evaluation, which were prominently distributed over the frontal, central, and temporal regions of the scalp. In the complex time-frequency domain, the extracted neural response characteristics exhibited distinct, statistically significant event-related synchronization within both the low-frequency δ and θ frequency bands, which was simultaneously accompanied by a widespread, prominent event-related desynchronization within the higher α band. A comparative analysis of model performance demonstrated that MS-STAMNet achieved an average unweighted average recall (UAR) of (69.67±6.12)% and area under the curve (AUC) of 0.761 8±0.07, significantly outperforming the established baseline models such as EEGNet and PLNet. Furthermore, a distinct dissociation phenomenon was verified between neural decoding and behavioral performance through regression analysis (R²=0.016, P=0.709), indicating that this model can effectively capture the implicit features of subtle frequency deviations, even when they fail to trigger explicit conscious responses. Additionally, attention weight visualization analysis further reveals the highly accurate focus of the network on key features concentrated over the bilateral temporal and fronto-parietal regions. ConclusionThis study systematically and comprehensively uncovers the multi-dimensional spatiotemporal evolutionary patterns of complex neural responses processing subtle acoustic variations under long-sequence threshold auditory stimulation. Concurrently, it verifies the efficacy and robustness of the proposed MS-STAMNet architecture in accurately deciphering weak, single-trial electroencephalogram signals amidst complex background noise. Ultimately, these neurophysiological and algorithmic findings lay a solid theoretical and methodological foundation for the objective and quantitative evaluation of individual auditory cognitive capabilities in clinical applications, transcending the fundamental limitations of traditional behavioral paradigms and providing robust technical support for future auditory research and related clinical assessments.

Aim To investigate the effects of Agrimonia pilosa(AP)on the proliferation and apoptosis of non-small cell lung cancer(NSCLC)H1299 cells using non-targeted metabolomics and other methods,and to explore the underlying molecular mechanisms.Meth-ods Taking H1299 cells as the research object,the effect of AP on cell proliferation and apoptosis was de-tected through CCK-8 method,colony formation,LDH,Hoechst 33258 staining,AO/EB staining,flow cytometry detection,RT qPCR and other experiments.The main differential metabolites were detected by the metabolomics method of ultra-high phase liquid chro-matography and mass spectrometry(UHPLC-Q-Orbi-trap MS),and related metabolic pathways were ana-lyzed.Results Compared with the control group,AP treatment was able to significantly inhibit the prolifera-tion and colony formation of H1299 cells,while the re-lease of LDH increased in a dose-dependent manner.Fluorescence microscopy and flow cytometry and RT-qPCR analysis revealed that H1299 cells underwent crumpling and increased nuclear fragmentation after AP administration,blocked in G0/G1 phase,up-regulated apoptotic genes caspase-3 and Bax,and down-regulated apoptosis-inducing effects of Bcl-2.Metabolomics anal-ysis screened 35 differential metabolites,which were PC(O-30∶1),D-Glutamic acid,PE(18∶0/15∶0),etc.The main metabolic pathways involved includ-ed amino acid metabolism,glycerophospholipid metabo-lism and purine metabolism so on.Conclusions AP may exert its pharmacological effects by interfering with multiple metabolic pathways in H1299 cells,inhibiting cell proliferation and promoting apoptosis.

Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30％and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P＜0.001],the degree of stenosis was significantly reduced[(13.24±6.60)％vs.(65.18±10.59)％,P＜0.001].Procedural success was achieved in 100％of cases,and device success was 98.8％.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P＜0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P＜0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P＜0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P＜0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.

Aim To investigate the effects of Agrimonia pilosa(AP)on the proliferation and apoptosis of non-small cell lung cancer(NSCLC)H1299 cells using non-targeted metabolomics and other methods,and to explore the underlying molecular mechanisms.Meth-ods Taking H1299 cells as the research object,the effect of AP on cell proliferation and apoptosis was de-tected through CCK-8 method,colony formation,LDH,Hoechst 33258 staining,AO/EB staining,flow cytometry detection,RT qPCR and other experiments.The main differential metabolites were detected by the metabolomics method of ultra-high phase liquid chro-matography and mass spectrometry(UHPLC-Q-Orbi-trap MS),and related metabolic pathways were ana-lyzed.Results Compared with the control group,AP treatment was able to significantly inhibit the prolifera-tion and colony formation of H1299 cells,while the re-lease of LDH increased in a dose-dependent manner.Fluorescence microscopy and flow cytometry and RT-qPCR analysis revealed that H1299 cells underwent crumpling and increased nuclear fragmentation after AP administration,blocked in G0/G1 phase,up-regulated apoptotic genes caspase-3 and Bax,and down-regulated apoptosis-inducing effects of Bcl-2.Metabolomics anal-ysis screened 35 differential metabolites,which were PC(O-30∶1),D-Glutamic acid,PE(18∶0/15∶0),etc.The main metabolic pathways involved includ-ed amino acid metabolism,glycerophospholipid metabo-lism and purine metabolism so on.Conclusions AP may exert its pharmacological effects by interfering with multiple metabolic pathways in H1299 cells,inhibiting cell proliferation and promoting apoptosis.

Objective:To observe the effects of auricular point compression and exercise therapy on glycolipid metabolism,oxidative stress and sleep quality in type 2 diabetes mellitus(T2DM)patients with poor glycemic control.Methods:This study was a single-center randomized controlled study,86 T2DM patients with poor glycemic control who were treated in our hospital from June 2022 to June 2024 were divided into control group(received conventional treatment,n=43)and observation group(received auricular point compression and exercise therapy,n=43)by using the random number table method.The clinical efficacy,blood lipid indexes,blood glucose indexes,oxidative stress indexes and sleep quality were compared between the two groups.Results:The total clinical effective rate,high-density lipoprotein cholesterol(HDL-C),superoxide dismutase(SOD)and Glutathione peroxidase(GSH-Px)of the observation group after treatment were higher than those of the control group,and the fasting blood glucose(FBG),glycated hemoglobin(HbA1c),Homeostatic Model Assessment of Insulin Resistance(HOMA-IR),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),triglycerides(TG),reactive oxygen species(ROS),malondialdehyde(MDA)and Pittsburgh sleep Quality Index(PSQI)score were lower than those of the control group(P＜0.05).Conclusion:Auricular point compression and exercise therapy can regulate glycolipid metabolism in T2DM patients with poor glycemic control,improve the degree of oxidative stress and sleep quality.

The pathological mechanisms and related physiological indicators of acute mountain sickness(AMS)were introduced,and the present situation of wearable devices applied in AMS auxiliary detection and diagnosis were reviewed.The challenges and future development directions of wearable devices applied in auxiliary detection and diagnosis were pointed out.[Chinese Medical Equipment Journal,2025,46(9):100-107]

Objective:To assess the predictive value for the risk of cardiogenic stroke (CS) in patients with paroxysmal atrial fibrillation (PAF) using quantification of left atrial appendage early blood stasis (LAA-BS) signs derived from left atrium-pulmonary vein CT examination.Methods:A retrospective analysis of 187 patients with PAF, who were confirmed to have LAA-BS by left atrium-pulmonary vein CT examinations, was conducted at Second Affiliated Hospital of Nantong University from January 2019 to December 2021. The ratio of LAA-BS CT values to ascending aorta (AA) CT values (HU BS/HU AA) and the ratio of LAA-BS volume to LAA volume (V BS/V LAA) were measured at the peak time of AA enhancement, which were used as characteristic quantitative indicators of LAA-BS. Using the median values of HU BS/HU AA and V BS/V LAA as cut-off points for grouping, the differences between the high-ratio and low-ratio groups were compared in terms of general information, clinical characteristics, and imaging characteristics. All enrolled patients were followed up with the primary outcome event of CS occurrence. The differences in the proportion of CS occurrence between the high-ratio and low-ratio groups were compared. The risk stratification analysis of the occurrence of CS in PAF patients was performed using Kaplan-Meier curves. Additionally, the predictive value of HU BS/HU AA, V BS/V LAA and other imaging indices for the risk of CS occurrence was assessed using Cox proportional risk regression models. Results:The incidence of hypertension and the proportion of patients with atrial fibrillation-stroke risk score (CHA 2DS 2-VASc)≥3 in the high V BS/V LAA group were higher than that in the low V BS/V LAA group, and the difference was statistically significant ( P=0.041, P=0.011). The left atrial volume (LAV) in patients in the low HU BS/HU AA group was greater than in the high HU BS/HU AA group, and the difference was statistically significant ( P=0.040). Kaplan-Meier analysis showed a higher incidence of CS in the low HU BS/HU AA group than in the high HU BS/HU AA group ( P=0.012). Similarly, the high V BS/V LAA group had a higher incidence of CS compared with the low V BS/V LAA group ( P=0.019). Subgroup analysis revealed a significantly higher incidence of CS in the subgroup with low HU BS/HU AA and high V BS/V LAA compared to other subgroups (all P<0.05). The Cox proportional hazards regression model, adjusting for confounding factors, identified low HU BS/HU AA and high V BS/V LAA as independent risk factors for CS occurrence in PAF patients ( P=0.005 and P=0.029). Conclusion:The HU BS/HU AA and V BS/V LAA quantified using left atrium-pulmonary vein CT imaging are predictive factors for CS occurrence in patients with PAF. These ratios synergistically contribute to the risk assessment of CS.

Inflammatory bowel disease is a chronic, idiopathic, and recurrent gastrointestinal disorder with an unclear etiology and uncertain pathogenesis. Traditional treatment strategies rely on frequent administration of high doses of medication to reduce inflammation, whereas these approaches have limitations and may induce potential complications. Therefore, finding more effective and safe therapeutic drugs and methods is particularly important. Plant-derived exosome-like nanovesicles(PDELNs) are nano-sized vesicles with a lipid bilayer structure that are secreted by plant cells. The bioactive molecules contained within, such as lipids, proteins, and nucleic acids, can serve as information carriers, playing a role in the transmission of information and substances between cells and across species. PDELNs can carry and transfer their own bioactive substances or act as carriers for delivering other active components or drugs. Due to the high biocompatibility, low toxicity, and significant bioactivity, PDELNs have garnered widespread attention. Compared with other exosomes, PDELNs are not destroyed in the gastrointestinal tract when taken orally and can reach the intestines. This unique property makes PDELNs a promising oral nanodrug for treating intestinal diseases, showing great potential in this area. This article reviews recent research literature on PDELNs regarding the physicochemical characteristics, extraction and purification methods, functions, application characteristics and mechanisms in the treatment of intestinal diseases, and use as a carrier for treating intestinal diseases, aiming to provide a reference for the use of PDELNs in the treatment of intestinal diseases.
Humans ; Exosomes/metabolism* ; Animals ; Intestinal Diseases/metabolism* ; Plants/metabolism* ; Drug Carriers/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Drug Delivery Systems ; Nanoparticles/chemistry*

Acute lung injury(ALI) is a critical clinical condition primarily characterized by refractory hypoxemia and infiltration of inflammatory cells in lung tissue, which can progress into a more severe form known as acute respiratory distress syndrome(ARDS). Immune cells and inflammatory cytokines play important roles in the progression of the disease. Due to its unclear pathogenesis and the lack of effective clinical treatments, ALI is associated with a high mortality rate and severely affects patients' quality of life, making the search for effective therapeutic agents particularly urgent. Ginseng Radix et Rhizoma, the dried root of the perennial herb Panax ginseng from the Araliaceae family, contains active ingredients such as saponins and polysaccharides, which possess various pharmacological effects including anti-tumor activity, immune regulation, and metabolic modulation. In recent years, studies have shown that ginsenosides exhibit notable effects in reducing inflammation, ameliorating epithelial and endothelial cell injury, and providing anticoagulant action, indicating their comprehensive role in alleviating lung injury. This review summarizes the pathogenesis of ALI and the molecular mechanisms through which ginsenosides act at different stages of ALI development. The aim is to provide a scientific reference for the development of ginsenoside-based drugs targeting ALI, as well as a theoretical basis for the clinical application of Ginseng Radix et Rhizoma in the treatment of ALI.
Ginsenosides/pharmacology* ; Humans ; Acute Lung Injury/immunology* ; Animals ; Panax/chemistry* ; Drugs, Chinese Herbal

BACKGROUND: The effects of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment on coronavirus disease 2019 (COVID-19) patients have been preliminarily characterized. However, real-world data on the safety and efficacy of intravenous transfusions of MSCs in hospitalized COVID-19 patients at the convalescent stage remain to be reported. METHODS: This was a single-arm, multicenter, real-word study in which a contemporaneous external control was included as the control group. Besides, severe and critical COVID-19 patients were considered together as the severe group, given the small number of critical patients. For a total of 110 patients, 21 moderate patients and 31 severe patients were enrolled in the MSC treatment group, while 26 moderate patients and 32 severe patients were enrolled in the control group. All patients received standard treatment. The MSC treatment patients additionally received intravenous infusions of MSCs at a dose of 4 × 10 7 cells on days 0, 3, and 6, respectively. The clinical outcomes, including adverse events (AEs), lung lesion proportion on chest computed tomography, pulmonary function, 6-min walking distance (6-MWD), clinical symptoms, and laboratory parameters, were measured on days 28, 90, 180, 270, and 360 during the follow-up visits. RESULTS: In patients with moderate COVID-19, MSC treatment improved pulmonary function parameters, including forced expiratory volume in the first second (FEV1) and maximum forced vital capacity (VCmax) on days 28 (FEV1, 2.75 [2.35, 3.23] vs . 2.11 [1.96, 2.35], P  = 0.008; VCmax, 2.92 [2.55, 3.60] vs . 2.47 [2.18, 2.68], P  = 0.041), 90 (FEV1, 2.93 [2.63, 3.27] vs . 2.38 [2.24, 2.63], P  = 0.017; VCmax, 3.52 [3.02, 3.80] vs . 2.59 [2.45, 3.15], P  = 0.017), and 360 (FEV1, 2.91 [2.75, 3.18] vs . 2.30 [2.16, 2.70], P  = 0.019; VCmax,3.61 [3.35, 3.97] vs . 2.69 [2.56, 3.23], P  = 0.036) compared with the controls. In addition, in severe patients, MSC treatment notably reduced the proportion of ground-glass lesions in the whole lung volume on day 90 ( P  = 0.045) compared with the controls. No difference in the incidence of AEs was observed between the two groups. Similarly, no significant differences were found in the 6-MWD, D-dimer levels, or interleukin-6 concentrations between the MSC and control groups. CONCLUSIONS: Our results demonstrate the safety and potential of MSC treatment for improved lung lesions and pulmonary function in convalescent COVID-19 patients. However, comprehensive and long-term studies are required to confirm the efficacy of MSC treatment. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR2000031430.
Humans ; COVID-19/therapy* ; Female ; Male ; Mesenchymal Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adult ; Umbilical Cord/cytology* ; Mesenchymal Stem Cells/cytology* ; SARS-CoV-2 ; Aged ; Treatment Outcome