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 investigate the relationship between tooth loss and the occurrence of esophageal cancer in a natural village in Wenfeng District, Anyang City, Henan Province. Methods A prospective cohort study was conducted to observe the occurrence of tooth loss and esophageal cancer among the asymptomatic residents of the natural village for 16 years from January 2008 to July 2024. Data were analyzed by chi-square test, binary logistic regression, and restricted cubic spline. Results Among the total population of 711 cases, 136 cases were lost to follow-up and 575 cases were included in the final statistics, including 45 cases with esophageal cancer. Significant statistical difference was found between esophageal cancer patients with and without tooth loss (P<0.05). Logistic regression analysis showed that tooth loss was associated with the occurrence of esophageal cancer (OR=3.977, 95%CI: 1.543-10.255). After the adjustment for confounders, tooth loss remained significantly associated with the occurrence of esophageal cancer (OR=3.038, 95%CI: 1.035-8.914). A nonlinear dose-response relationship was observed between the number of teeth lost and the incidence of esophageal cancer. When the number of teeth lost was less than 12, the risk of esophageal cancer increased with the number of teeth lost. When more than 12 teeth were lost, the risk of esophageal cancer decreased as the number of teeth lost increased. Conclusion Tooth loss is a risk factor for the occurrence of esophageal cancer in this natural village. When the number of teeth lost is less than 12, the risk of esophageal cancer increases with the number of teeth lost.

Thyroid hormone（TH）plays an important role in human development and is involved in gene and protein expression in almost all tissues，especially in the development of the central nervous system.TH requires a TH transporter to enter the cell，and three families of TH transporter proteins are known，namely monocarboxylate transporters（MCTs），organic anion transporting polypeptides（OATPs）and L-type amino acid transporter（LAT）.MCT8 has been found to be a specific TH transporter，and OATP1C1 also plays an important role.Deficiency of TH transporters may lead to different degrees of dysfunction in the nervous system and endocrine system.Currently，more studies have been conducted on MCT8 deficiency，which presents with characteristic psychomotor retardation and TH abnormalities，and there are no specific treatment options.In this paper，we summarize the research progress on clinical phenotype，pathogenic mechanism，and treatment of thyroid hormone transporter defects related diseases to provide reference for clinical research.

A 67-year-old male had undergone bilateral lung transplantation for chronic obstructive pulmonary disease 11 months before the current presentation. He was admitted with a 5-day history of cough with sputum, and a 2-day history of fever. Computed tomography (CT) of the chest revealed rapidly progressive bilateral diffuse "ground glass" opacities. Despite anti-infective therapy and methylprednisolone pulse therapy, his condition deteriorated, necessitating endotracheal intubation with mechanical ventilation and veno-venous extracorporeal membrane oxygenation (V-V ECMO) for life support. A bedside cryobiopsy was undertaken, with pathology confirming the organizing pneumonia diagnosis. Comprehensive treatment was continued: methylprednisolone, tacrolimus for immunosuppression, and prophylactic anti-infectives. His partial pressure of oxygen in the blood by the fraction of inspired oxygen ratio and imaging findings improved gradually. ECMO support was discontinued after 2 weeks, and he was discharged 1-month later, resuming normal daily activities. At 2-month follow-up, he exhibited improved exercise tolerance. Chest CT showed bilateral upper-lobe emphysema (predominantly upper-lobe reticular shadows) and significant bilateral upper-lobe pleural thickening. After 12 months of fllow-up, a diagnosis of chronic lung allograft dysfunction was made based on imaging findings and the trajectory of pulmonary function.

A 67-year-old male had undergone bilateral lung transplantation for chronic obstructive pulmonary disease 11 months before the current presentation. He was admitted with a 5-day history of cough with sputum, and a 2-day history of fever. Computed tomography (CT) of the chest revealed rapidly progressive bilateral diffuse "ground glass" opacities. Despite anti-infective therapy and methylprednisolone pulse therapy, his condition deteriorated, necessitating endotracheal intubation with mechanical ventilation and veno-venous extracorporeal membrane oxygenation (V-V ECMO) for life support. A bedside cryobiopsy was undertaken, with pathology confirming the organizing pneumonia diagnosis. Comprehensive treatment was continued: methylprednisolone, tacrolimus for immunosuppression, and prophylactic anti-infectives. His partial pressure of oxygen in the blood by the fraction of inspired oxygen ratio and imaging findings improved gradually. ECMO support was discontinued after 2 weeks, and he was discharged 1-month later, resuming normal daily activities. At 2-month follow-up, he exhibited improved exercise tolerance. Chest CT showed bilateral upper-lobe emphysema (predominantly upper-lobe reticular shadows) and significant bilateral upper-lobe pleural thickening. After 12 months of fllow-up, a diagnosis of chronic lung allograft dysfunction was made based on imaging findings and the trajectory of pulmonary function.

Objective:To investigate the relationship between the weight-adjusted waist index(WWI)and acute,subacute pain or chronic pain among American adults.Methods:There was a cross-sectional study.Data from the 1999-2004 National Health and Nutrition Examination Survey(NHANES)con-cerning waist circumference,weight,pain status and covariates(age,gender,race,marital status,edu-cation level and income,physical activity,alcohol consumption,smoking status,and diabetes)were extracted for analysis.Multinomial Logistic regression was conducted across the three models to investi-gate the associations between WWI and acute,subacute and chronic pain.Model 1 did not involve any adjustments.Model 2 involved adjustments for age,gender,race,marital status,education level,and income.Model 3 was further adjusted for physical activity,alcohol consumption,smoking,and diabetes status.Results:This study involved 12 694 participants with an average age of(50.6±18.7)years.Among all the participants,9 614 people(75.74％)had no pain,870 people(6.85％)experienced acute pain,354 people(2.79％)suffered from subacute pain,and 1 856 people(14.62％)experienced chronic pain.The WWI of all the participants was(10.95±0.85)cm/√kg,divided into four groups based on quartiles:Group Q1(7.90-10.36)cm/√kg,group Q2(10.37-10.94)cm/√kg,group Q3(10.95-11.53)cm/√kg and group Q4(11.54-15.20)cm/√kg.With the increase of WWI,the analysis revealed a significant statistical difference in the participants'acute and chronic pain status(all P＜0.001).In Model 1,the prevalence of acute pain was lower in group Q2 and group Q4 compared with group Q1(group Q2:OR=0.765,95％CI:0.615-0.953,P=0.017;group Q4:OR=0.648,95％CI:0.503-0.835,P＜0.001).Compared with group Q1,the prevalence of chronic pain increased in group Q2,group Q3,and group Q4(group Q2:OR=1.365,95％CI:1.149-1.622,P＜0.001;group Q3:OR=1.291,95％CI:1.082-1.541,P=0.005;group Q4:OR=1.874,95％CI:1.579-2.224,P＜0.001).In Model 2,compared with group Q1,an increase in chronic pain preva-lence was still associated with an increase in WWI in other three groups(group Q2:OR=1.359,95％CI:1.137-1.624,P=0.001;group Q3:OR=1.260,95％CI:1.039-1.528,P=0.019;group Q4:OR=1.735,95％CI:1.413-2.132,P＜0.001).In Model 3,group Q4 had a 49.2％increased prevalence of chronic pain compared to group Q1(OR=1.492,95％CI:1.208-1.842,P＜0.001).However,in Models 2 and 3,no significant relationship was observed between acute pain and WWI(all P＞0.05).And none of the three models identified a significant association between subacute pain and WWI(all P＞0.05).Conclusion:For American adults,there was no significant correlation between WWI and acute pain or subacute pain.However,as WWI increases,so does the prevalence of chronic pain.Further validation of this conclusion through large-scale prospective studies is warranted.

Aim To establish a quantitative immunofluorescent bioactivity assay(ICW)for insulin glargine based on CHO-IN-SRB 1284 transgenic cells,and to study its equivalence with in-sulin bioassay of Ch.P.Methods The cells were diluted 25 times with 1.5 × 108 L-1 cell density plates and 1 500 μmol·L-1 insulin glargine,and then diluted with a 3-fold gradient se-ries.The cells were stimulated in microporous plates for 20 min.After fixation,permeation and antibody incubation.Quantitative immunofluorescence biological activity was detected by odyssey two-color infrared fluorescence imaging system.Results There was a good dose-effect relationship between the concentration of insulin glargine in ICW and its relative potency.The method had good specificity,and the relative accuracy,intermediate preci-sion and linearity met the requirements.The relative deviation of biological activity results of 7 batches of insulin glargine samples measured by the two methods was less than 10％.The results were analyzed by SPSS and SAS software,which showed that the methods were correlated and equivalent.Conclusions The quantitative immunofluorescence assay for the biological activity of insulin glargine can be established.The method has good spe-cificity,high accuracy and precision,and has correlation and e-quivalent with biotiter assay,which can be applied to in vitro ef-ficacy evaluation and quality control of insulin glargine.

AIM To study endophytic fungi from Scutellaria baicalensis Georgi.and the enzyme inhibitory activities of their secondary metabolites.METHODS Six different media were used to isolate and purify endophytic fungi from S.baicalensis by tissue homogenate method.The activities of secondary metabolites were evaluated by targeting different enzymes.The highly active strains were identified by molecular biology combined with morphology,and the highly active chemical components were tracked and separated by modern chromatographic separation technology.RESULTS Sixty-four endophytic fungal strains were isolated from S.baicalensis,and one hundred and twenty-eight secondary metabolites were obtained by fermentation.The samples with certain inhibitory activities against adenosine deaminase(ADA),β-lactamase and tyrosinase(TYR)accounted for 14.06%,3.91%and 18.75%,respectively.Strain HTS-23-2 showed high TYR inhibitory activity,and 99%homology with Aspergillus flavus by molecular identification.One compound was isolated from the fermentation samples and identified as kojic acid.CONCLUSION S.baicalensis harbors a rich diversity of endophytic fungi,which serve as a valuable resource for active substances.

A 49-year-old female examinee, employed at a paper company in Guigang, Guangxi (engaged in the production of napkins), visited the Qintang District People′s Hospital in Guigang on June 11, 2023, to apply for a health certificate. Salmonella was isolated during a physical examination screening for enteric pathogens ( Salmonella, Shigella), and repeated use of empirical antibacterial drugs failed to eradicate the pathogen. A reference laboratory identified the two isolates as S. Kentucky ST198 by performing serotyping, drug resistance phenotyping, and whole genome sequencing. Based on the regional serotype database of Salmonella in China, a phylogenetic tree of S. Kentucky ST198 resistance genotypes was constructed, defining both isolated strains as high-level drug-resistant ST198.2-1 subclade clones. Following a multidisciplinary consultation and based on antimicrobial susceptibility test results, the treatment was adjusted to amoxicillin/clavulanate and azithromycin. On August 19, three consecutive negative test results confirmed the eradication of Salmonella Kentucky.

Objective To observe the clinical efficacy of compound Wufengcao liquid combined with negative pressure wound therapy with instillation(NPWTi)for the treatment of stage Ⅲ-Ⅳ pressure injury(PI),and to preliminarily explore its action mechanism.Methods(1)Clinical research:from January 2019 to October 2022,60 PI patients who were admitted to the Scrofula Department and Wound Care Clinic at Nanjing Municipal Hospital of Traditional Chinese and Western Medicine were randomly divided into normal saline NPWTi group and compound Wufengcao liquid NPWTi group,with 30 cases in each group.Both groups underwent NPWTi under the premise of systemic basic treatment,before treatment,after removing the negative pressure device in the 1st,2nd and 3rd weeks of treatment,the pressure ulcer scale for healing(PUSH)score,the wound bacterial culture detection rate and the wound healing time were counted,and the vascular endothelial growth factor(VEGF)content of wound tissue was detected by ELISA method.(2)Animal experiments:24 SD rats were randomly divided into blank group,model group,normal saline NPWTi group and compound Wufengcao liquid NPWTi group,6 rats in each group.PI rat model was established by local tissue ischemia/reperfusion injury method,and the negative pressure device was removed at the end of each day of treatment.Before treatment and 3,7 and 10 days after treatment,the wound morphology of each group of rats was observed,the wound histopathology was observed by HE staining,the CD34 positive cells rate of wound tissue was detected by immunohistochemistry,and the expressions of p38 mitogen-activated protein kinase(p38 MAPK),nuclear factor-κB p65(NF-κB p65),inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),arginase-1(Arg-1)and transforming growth factor-β(TGF-β)in rat blood and wound tissue were detected by ELISA and RT-qPCR.Results(1)Clinical research:Both groups could effectively reduce the PUSH score and the wound bacterial culture detection rate,shorten the wound healing time,and promote the expression of VEGF in wound tissue,the compound Wufengcao liquid NPWTi group was better than the normal saline NPWTi group(P<0.05).(2)Animal experiments:Compared with blank group,the rats in the model group showed obvious wound inflammatory response and tissue damage,and the CD34 positive cells rate,blood and wound tissue p38 MAPK,NF-κB p65,iNOS and TNF-α levels were significantly increased,Arg-1 and TGF-β level was significantly reduced(P<0.05);Compared with model group,after 7 days of treatment,the normal saline NPWTi group and the compound Wufengcao liquid NPWTi group significantly decreased the wound morphology score,the histopathological morphology was significantly improved,the CD34 positive cells rate was significantly increased(P<0.05),the levels of blood and wound tissue p38 MAPK,NF-κB p65,iNOS,and TNF-α were significantly reduced,and the levels of Arg-1 and TGF-β were significantly increased(P<0.05),and the compound Wufengcao liquid NPWTi group was better than that of the normal saline NPWTi group(P<0.05).Conclusion Compound Wufengcao liquid combined with NPWTi can effectively promote the healing of PI wounds,and its mechanism of action may be by inhibiting the activation and expression of p38 MAPK/NF-κB signaling pathway,thereby regulating the polarization balance of M1/M2 macrophages.