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.

Objective To establish an HPLC method to determine the concentration of inositol nicotinate（IN） in rat skin, and study the pharmacokinetic characteristics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats. Methods HPLC method was used to establish a simple and rapid analytical method for the determination of IN concentration in the skin of rats at different time points after administration. The established method was used to study the pharmacokinetics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats, and the pharmacokinetic parameters were fitted with DAS software. Results The linearity of the analytical method was good in the concentration range of 0.25-20 μg/ml, the quantitative limit was 0.25 μg/ml, and the average recovery rate was 96.18%. The pharmacokinetic parameters of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats were as follows: t_1/2 was （4.555±2.054） h, T_max was （6±0）h, C_max was （16.929±2.153）mg/L, AUC_0−t was （150.665±16.568） mg·h /L ,AUC_0−∞ was （161.074±23.917） mg·h /L, MRT_（0−t） was （9.044±0.618）h, MRT_{（0−∞）} was （10.444±1.91） h, CLz/F was （0.19±0.03） L/（h·kg）, and Vz/F was （1.19±0.437） L/（h·kg）. Conclusion IN could quickly penetrate the skin and accumulate in the skin for a long time, which was beneficial to the pharmacological action of drugs on the lesion site for a long time. The method is simple, rapid, specific and reproducible, which could be successfully applied to the pharmacokinetic study of IN after transdermal administration in rats.

Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

Sustained inflammatory responses are closely related to various severe diseases,and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment.Natural products have garnered considerable concern for the treatment of inflammation.Huanglian-Wumei decoction(HLWMD)is a classic prescription used for treating inflammatory diseases,but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated.Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory,we successfully obtained berberine(BBR)-chlorogenic acid(CGA)supramolecular(BCS),which is an herbal pair from HLWMD.Using a series of characterization methods,we confirmed the self-assembly mechanism of BCS.BBR and CGA were self-assembled and stacked into amphiphilic spherical supra-molecules in a 2:1 molar ratio,driven by electrostatic interactions,hydrophobic interactions,and π-πstacking;the hydrophilic fragments of CGA were outside,and the hydrophobic fragments of BBR were inside.This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules.Compared with free molecules,BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide(LPS)-induced pyroptosis.Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB(NF-κB)p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

Anti-leucine-rich glioma-inactivated 1 protein (LGI1) antibody-associated encephalitis is an autoimmune encephalitis mediated by LGI1 antibodies, which can occur in both adults and children. Its common clinical manifestations include epileptic seizures, cognitive and psychiatric disorders; rare symptoms include sleep disorders and autonomic disorders; and its characteristic manifestations are faciobrachial dystonic seizures and refractory hyponatremia. Since anti-LGI1 antibody-associated encephalitis is relatively rare in clinical practice, this article reviews the disease in terms of etiology and pathogenesis, clinical manifestations, auxiliary examinations, diagnosis and differential diagnosis, treatment, recurrence and prognosis. It aims to improve clinicians′ understanding of this disease, provide references for its early diagnosis and treatment, and thereby improve patients′ prognosis.

Objective To conduct a scoping review of the intervention design and application status of intelligent interactive cognitive-motor training(IICMT)in fall prevention among older adults,providing references for subsequent research in this field.Methods Following the scoping review framework,systematic searches were conducted in PubMed,Web of Science,Embase,Cochrane Library,CINAHL,Scopus,IEEE Xplore,Chinese Biomedical Literature Database,CNKI,Wanfang Database,and VIP Database from their inception to September 17,2024.The included studies were analyzed and summarized.Results A total of 19 articles were included.The main intelligent interactive technologies included virtual reality,commercial games,computer touch sensing,wearable devices,and infrared sensing,typically combining basic cognitive ability training,advanced cognitive function training,spatial cognitive training,and comprehensive application training with functional activity training such as balance and coordination,gait and strength,stair climbing,and obstacle avoidance.Assessment indicators included balance and gait,fall risk and self-efficacy,physiological indicators,muscle strength,postural stability,physical function,as well as feasibility and safety assessments.Conclusion IICMT is safe and feasible among older adults,and can improve balance and fall efficacy,reducing the risk of falls.

Anti-leucine-rich glioma-inactivated 1 protein (LGI1) antibody-associated encephalitis is an autoimmune encephalitis mediated by LGI1 antibodies, which can occur in both adults and children. Its common clinical manifestations include epileptic seizures, cognitive and psychiatric disorders; rare symptoms include sleep disorders and autonomic disorders; and its characteristic manifestations are faciobrachial dystonic seizures and refractory hyponatremia. Since anti-LGI1 antibody-associated encephalitis is relatively rare in clinical practice, this article reviews the disease in terms of etiology and pathogenesis, clinical manifestations, auxiliary examinations, diagnosis and differential diagnosis, treatment, recurrence and prognosis. It aims to improve clinicians′ understanding of this disease, provide references for its early diagnosis and treatment, and thereby improve patients′ prognosis.

Objective To evaluate the impact of intensified infection control measures on the incidence of health-care-associated infection(HAI)under the background of the reform of diagnosis-intervention packet(DIP)payment,and provide decision-making basis for HAI management under the reform of medical insurance payment.Methods The interrupted time series research design was used to collect the monitoring data of HAI in a tertiary first-class hospital from October 2021 to September 2024.The changing trend of HAI incidence was analyzed by piecewise li-near regression,and the intervention effect was evaluated by standardized infection ratio(SIR).Results From Oc-tober 2021 to September 2022,the incidence of HAI was 2.17％(95％CI:2.08％-2.26％),which dropped to 1.87％(95％CI:1.82％-1.92％)after the intervention.Piecewise linear regression analysis showed that the inci-dence of HAI decreased by 0.324％immediately after the intervention(95％CI:-0.481％--0.167％,P＜0.001),and the trend after the intervention changed significantly compared with that before the intervention(95％CI:-0.033％--0.009％,P=0.001).SIR analysis showed that the actual incidence during the entire intervention period was equivalent to 74.56％of the incidence in intervention period,gradually stabilized from 88.39％-93.81％at the beginning of the intervention to 67.03％-71.22％at the end of the study,and the intervention effect was sustained.Conclusion Intensified infection control measures under the background of the reform of DIP significantly reduce the incidence of HAI and improve the stability of infection control management,which provide new insights into the synergistic improvement of medical insurance payment and HAI management quality.

Objective To conduct a scoping review of the intervention design and application status of intelligent interactive cognitive-motor training(IICMT)in fall prevention among older adults,providing references for subsequent research in this field.Methods Following the scoping review framework,systematic searches were conducted in PubMed,Web of Science,Embase,Cochrane Library,CINAHL,Scopus,IEEE Xplore,Chinese Biomedical Literature Database,CNKI,Wanfang Database,and VIP Database from their inception to September 17,2024.The included studies were analyzed and summarized.Results A total of 19 articles were included.The main intelligent interactive technologies included virtual reality,commercial games,computer touch sensing,wearable devices,and infrared sensing,typically combining basic cognitive ability training,advanced cognitive function training,spatial cognitive training,and comprehensive application training with functional activity training such as balance and coordination,gait and strength,stair climbing,and obstacle avoidance.Assessment indicators included balance and gait,fall risk and self-efficacy,physiological indicators,muscle strength,postural stability,physical function,as well as feasibility and safety assessments.Conclusion IICMT is safe and feasible among older adults,and can improve balance and fall efficacy,reducing the risk of falls.

Objective To evaluate the impact of intensified infection control measures on the incidence of health-care-associated infection(HAI)under the background of the reform of diagnosis-intervention packet(DIP)payment,and provide decision-making basis for HAI management under the reform of medical insurance payment.Methods The interrupted time series research design was used to collect the monitoring data of HAI in a tertiary first-class hospital from October 2021 to September 2024.The changing trend of HAI incidence was analyzed by piecewise li-near regression,and the intervention effect was evaluated by standardized infection ratio(SIR).Results From Oc-tober 2021 to September 2022,the incidence of HAI was 2.17％(95％CI:2.08％-2.26％),which dropped to 1.87％(95％CI:1.82％-1.92％)after the intervention.Piecewise linear regression analysis showed that the inci-dence of HAI decreased by 0.324％immediately after the intervention(95％CI:-0.481％--0.167％,P＜0.001),and the trend after the intervention changed significantly compared with that before the intervention(95％CI:-0.033％--0.009％,P=0.001).SIR analysis showed that the actual incidence during the entire intervention period was equivalent to 74.56％of the incidence in intervention period,gradually stabilized from 88.39％-93.81％at the beginning of the intervention to 67.03％-71.22％at the end of the study,and the intervention effect was sustained.Conclusion Intensified infection control measures under the background of the reform of DIP significantly reduce the incidence of HAI and improve the stability of infection control management,which provide new insights into the synergistic improvement of medical insurance payment and HAI management quality.