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 effects of moxibustion,filiform needle acupuncture,and electroacupuncture on synovial hypoxia and expression of synovial fibrosis markers[transforming growth factor(TGF)-β and collagen alpha-1(Ⅰ)chain(COL1A1)]in knee osteoarthritis(KOA)rats.Methods:Fifty Sprague-Dawley rats were randomly divided into a normal group,a model group,a moxibustion group,an acupuncture group,and an electroacupuncture group,with 10 rats in each group.Except for the normal group,rats in the other four groups were injected with sodium iodoacetate into the right knee joint cavity to establish KOA models.The right Futu(ST32)and Zusanli(ST36)were selected in the moxibustion,acupuncture,and electroacupuncture groups to perform the mild moxibustion with moxa sticks,filiform needle acupuncture,or electroacupuncture,respectively.Each intervention lasted 15 min,once every other day,and continued for 4 weeks,with a total of 14 interventions.The Lequesne score was used to evaluate the degree of knee dysfunction before and after intervention,and the rat's right knee joint diameter was measured to evaluate the degree of knee swelling.Morphological changes of the right knee joint synovial tissue were observed using hematoxylin-eosin staining.Hypoxia probe immunofluorescence staining was used to observe the degree of synovial hypoxia in rats.Western blotting was used to detect the protein expression levels of hypoxia-inducible factor(HIF)-1α,TGF-β,and COL1A1 in the synovial tissue of the right knee joints.Results:Before intervention,the Lequesne score and the right knee joint diameter in the other four groups increased significantly compared to the normal group(P<0.01).After intervention,the Lequesne score and the right knee joint diameter increased significantly in the model group compared to the normal group(P<0.01)together with worsened cartilage deformation and osteophytes,inflammatory cell infiltration and fibrosis in synovial tissue,and hypoxia degree,and the expression levels of HIF-1α,TGF-β,and COL1A1 proteins in the knee joint synovial tissue of rats increased(P<0.01).The Lequesne score and the right knee joint diameter decreased significantly(P<0.01 or P<0.05),the cartilage morphology was normal without obvious osteophytes,and the hypoxia degree reduced in the three intervention groups compared to the model group.Among them,the moxibustion group had the most notable improvement in hypoxia,synovial tissue fibrosis,angiogenesis,and inflammatory cell infiltration.The expression levels of HIF-1α,TGF-β,and COL1A1 proteins decreased in the moxibustion and electroacupuncture groups(P<0.01),and the expression levels of HIF-1α and TGF-β proteins were decreased in the acupuncture group(P<0.01).Conclusion:Moxibustion,filiform needle acupuncture,and electroacupuncture improve knee joint function and reduce knee joint swelling in KOA rats.The mechanism may be to improve synovial fibrosis of the knee joint by regulating HIF-1α;moxibustion has the best effect on improving hypoxia among the three interventions,but the effect of filiform needle acupuncture on COL1A1 is not significant.

Objective:This multicenter retrospective study aimed to analyze the clinicopathological features of duodenal adenocarcinoma (DA) and identify prognostic factors for postoperative survival.Methods:Demographic characteristics, clinicopathological features, treatment outcomes and survival of DA patients undergoing surgical treatment at 18 Chinese medical centers from January 2012 to December 2023 were retrospectively analyzed.Results:Among the 2 056 DA patients included, 46.8% (963) had extra-ampullary DA (EA-DA), and 53.2% (1 093) had peri-ampullary DA (PA-DA). The 1-, 3-, and 5-year overall survival (OS) rates for patients who underwent radical surgery were 93.2%, 71.0%, and 57.2%, respectively. The median overall survival was 76 months, and the median progression-free survival (PFS) was 65 months. No differences in survival were observed between the laparotomy group and minimally invasive surgery (MIS) group either before or after propensity score matching (OS: 76 vs. 75 months before PSM, P=0.986; OS: 75 vs. 75 months after PSM, P=0.602). Furthermore, there were no significant differences between-group in operation time and postoperative complications ( P＞0.05). The MIS group experienced less intraoperative blood loss and shorter hospital stays. The multivariate Cox regression analysis revealed that advanced age ( HR=1.43,95% CI:1.18-1.73), elevated carbohydrate antigen 19-9 levels ( HR=1.24,95% CI:1.02-1.51), perineural invasion ( HR=1.44,95% CI:1.14-1.81), vascular invasion ( HR=1.35,95% CI:1.07-1.71), advanced T stage (T3-4 vs. T1-2: HR=1.86,95% CI:1.49-2.31), regional lymph node metastasis ( HR=1.93,95% CI:1.58-2.36), preoperative biliary drainage ( HR=1.26,95% CI:1.04-1.53), intraoperative blood loss ( HR=1.34,95% CI:1.11-1.62), clinically significant postoperative pancreatic fistulas ( HR=1.53,95% CI:1.12-2.09), and postoperative hemorrhage ( HR=1.62,95% CI:1.14-2.29) were independent risk factors for poor prognosis after surgery (all P＜0.05). Conclusions:Radical surgery is associated with favorable overall survival among DA patients, and no difference in survival is observed between EA-DA and PA-DA patients. MIS is a reliable alternative for DA treatment.

Objective:To analyze factors influencing the melasma severity, and to evaluate the efficacy of different treatment modalities.Methods:A retrospective analysis was conducted on clinical data from patients diagnosed with melasma at the Pigmentary Disorders Specialty Clinic in the Department of Dermatology, Huashan Hospital, Fudan University from July 2018 to December 2023. Patients' Fitzpatrick skin types, lesion color, locations and subtypes were evaluated by dermatologists, the melasma area and severity index (MASI) scores were calculated, and ΔMASI scores (baseline MASI scores - post-treatment MASI scores) were used for efficacy evaluation. The t test and one-way analysis of variance were used to analyze factors influencing the severity of melasma, the paired t test was used to analyze the differences in MASI scores before and after treatment, and a multivariate linear regression model was established to analyze factors influencing the efficacy in the treatment of melasma. Results:A total of 254 patients (including 249 females, 98.0%) with melasma were included, with ages of 40.8 ± 6.1 years. The Fitzpatrick skin type was Ⅲ in 213 (83.9%) patients, and Ⅳ in 41 (16.1%) patients; 180 (70.9%) patients lacked the habit of using sunscreens regularly. According to the location of pigment deposition, 166 cases (65.4%) were classified as epidermal type, and 88 (34.6%) as mixed type. Pigmented lesions were located on the cheek (174 cases, 68.5%), midface (26 cases, 10.2%), or lower jaw (54 cases, 21.3%), with periorbital involvement observed in 127 cases (50.0%). Before treatment, baseline MASI scores were significantly higher in the skin type Ⅳ group (19.75 ± 5.08) than in the skin type Ⅲ group (14.47 ± 4.18, P < 0.001), in the non-sunscreen users (16.45 ± 4.61) than in the sunscreen users (12.59 ± 3.91, P < 0.001), in the epidermal type group (15.99 ± 4.82) than in the mixed type group (14.07 ± 4.35, P < 0.001), in the mandibular type group (18.37 ± 5.14) than in the midfacial type group (14.23 ± 3.46, P < 0.001) and malar type group (14.54 ± 4.40, P < 0.001), as well as in the patients with periorbital involvement (16.54 ± 4.90) than in those without (14.10 ± 4.26, P < 0.001). According to the main treatment regimens, the patients were divided into the topical 2% hydroquinone group (109 cases, topically treated with 2% hydroquinone cream nightly), topical non-hydroquinone skin-lightening agents group (36 cases, topically treated with non-hydroquinone skin-lightening or exfoliating agents), oral tranexamic acid group (50 cases, treated with oral tranexamic acid 250 mg twice daily), and alpha hydroxy acid (AHA) chemical peeling group (30 cases, receiving AHA chemical peeling treatment monthly with the AHA concentration escalating from 20% to 50%). After treatment, MASI scores were significantly reduced from baseline in all the 4 groups (all P < 0.001), and the ΔMASI values significantly differed among the topical 2% hydroquinone group, topical non-hydroquinone skin-lightening agents group, oral tranexamic acid group, and AHA chemical peeling group (1.65 ± 2.19, 1.40 ± 2.16, 4.58 ± 3.09, 3.39 ± 3.61, respectively, F = 17.40, P < 0.001). The oral tranexamic acid group and AHA chemical peeling group showed significantly superior efficacy compared to the topical 2% hydroquinone group and topical non-hydroquinone skin-lightening agents group (all P < 0.05), while there was no significant difference in the efficacy between the oral tranexamic acid group and the AHA chemical peeling group ( P > 0.05). After adjustment for potential confounders in the multivariate linear regression model, the oral tranexamic acid group (β = 2.64) and AHA chemical peeling group (β = 1.55) still showed significantly superior efficacy compared to the topical 2% hydroquinone group (both P < 0.05) ; the skin type Ⅳ group exhibited significantly superior efficacy compared to the skin type Ⅲ group (β = 1.87, P < 0.001) . Conclusions:Dark skin color, lack of sun protection habits, epidermal melasma, and mandibular-type melasma, and periorbital involvement were associated factors for the severity of melasma. Oral tranexamic acid and AHA chemical peeling appeared to exhibit superior efficacy compared to topical 2% hydroquinone cream and topical non-hydroquinone skin-lightening agents.

Nuclear medicine plays a pivotal role in diagnosis and treatment of tumors.The development of radionuclide probes with high affinity and specificity is an effective approach to achieve precise diagnosis and treatment of tumors.With high binding affinity,rapid tissue penetration and excellent pharmacokinetic properties,bicyclic peptide-based radionuclide probes demonstrate remarkable advantages in diagnosis and targeted therapy of tumors.The structural characteristics and design strategies of bicyclic peptide-based radionuclide probes were reviewed in this article,mainly focused on research progresses in targeting tumor-associated receptors.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To explore the quantitative indexes of dual energy spectrum CT and related clinical data to establish a predictive model for predicting pneumoconiosis.Methods:In April 2024, the information of 203 pneumoconiosis patients diagnosed by the occupational disease appraisal expert group in the Third People's Hospital of Xinjiang Uygur Autonomous Region (Occupational Disease Hospital of Xinjiang Autonomous Region) from January 2022 to December 2023 was retrospectively analyzed. Another 207 non-pneumoconiosis patients with dust exposure history were selected as control group. The measurement data between the two groups were compared using T test or Wilcoxon in dependent quality test, count date asing chi-square or Fishers test, the energy spectrum related indicators and clinical indicators of the patients were compared between groups, and potential factors for diagnosis of pneumoconiosis were screened through univariate analysis, and independent risk factors were further determined by multivariate logistic regression. Based on the results of regression analysis, the machine learning model was constructed, and the reciver operating characteristic curve (ROC) was drawn to evaluate the efficiency of the model, and the Area under cruve (AUC) value, sensitivity and specificity were calculated.Results:Smoking, lung tissue mass, silicon dioxide (SiO 2) equivalent total mass and SiO 2 equivalent concentration were the risk factors for pneumoconiosis ( P<0.05) . Multivariate logistic regression analysis showed that smoking, lung tissue mass, total lung SiO 2 equivalent total volume and total lung SiO 2 equivalent total mass were independent predicators of the diagnosis of pneumoconiosis ( OR=0.53, 0.99, 1.13, 0.85, P<0.05) . Logistic regression machine learning was used to establish a predictive model, and the training set AUC was 0.74, and the verification set AUC was 0.72, indicating that the model had good accuracy and certain ability to diagnose pneumoconiosis. Conclusion:The machine learning prediction model established by the quantitative analysis index of dual energy spectrum CT and clinical related indexes has a good diagnostic performance for the diagnosis of pneumoconiosis.

Objective:This multicenter retrospective study aimed to analyze the clinicopathological features of duodenal adenocarcinoma (DA) and identify prognostic factors for postoperative survival.Methods:Demographic characteristics, clinicopathological features, treatment outcomes and survival of DA patients undergoing surgical treatment at 18 Chinese medical centers from January 2012 to December 2023 were retrospectively analyzed.Results:Among the 2 056 DA patients included, 46.8% (963) had extra-ampullary DA (EA-DA), and 53.2% (1 093) had peri-ampullary DA (PA-DA). The 1-, 3-, and 5-year overall survival (OS) rates for patients who underwent radical surgery were 93.2%, 71.0%, and 57.2%, respectively. The median overall survival was 76 months, and the median progression-free survival (PFS) was 65 months. No differences in survival were observed between the laparotomy group and minimally invasive surgery (MIS) group either before or after propensity score matching (OS: 76 vs. 75 months before PSM, P=0.986; OS: 75 vs. 75 months after PSM, P=0.602). Furthermore, there were no significant differences between-group in operation time and postoperative complications ( P＞0.05). The MIS group experienced less intraoperative blood loss and shorter hospital stays. The multivariate Cox regression analysis revealed that advanced age ( HR=1.43,95% CI:1.18-1.73), elevated carbohydrate antigen 19-9 levels ( HR=1.24,95% CI:1.02-1.51), perineural invasion ( HR=1.44,95% CI:1.14-1.81), vascular invasion ( HR=1.35,95% CI:1.07-1.71), advanced T stage (T3-4 vs. T1-2: HR=1.86,95% CI:1.49-2.31), regional lymph node metastasis ( HR=1.93,95% CI:1.58-2.36), preoperative biliary drainage ( HR=1.26,95% CI:1.04-1.53), intraoperative blood loss ( HR=1.34,95% CI:1.11-1.62), clinically significant postoperative pancreatic fistulas ( HR=1.53,95% CI:1.12-2.09), and postoperative hemorrhage ( HR=1.62,95% CI:1.14-2.29) were independent risk factors for poor prognosis after surgery (all P＜0.05). Conclusions:Radical surgery is associated with favorable overall survival among DA patients, and no difference in survival is observed between EA-DA and PA-DA patients. MIS is a reliable alternative for DA treatment.

This study aims to investigate the epidemic variation of porcine circovirus type2(PCV2)and its distribution in swine farms in Henan Province from 2022 to 2023.In this study,1 206 pig blood samples from 18 urban scale swine farms,and 318 pigs and environmental samples from 2 PCV2-positive swine farms in Henan Province were detected by fluorescence quantitative PCR.ORF2 gene sequencing and genetic evolution analysis were performed on the positive samples.The results showed that the positive rate of PCV2 was 7.05％(85/1 206)in Henan Province,11.15％in western Henan Province and 3.03％in southern Henan Province.The positive rate of PCV2 in spring was 11.60％(67/576).A total of 31 ORF2 gene sequences were obtained,of which 23 were PCV2d(74.19％),6 were PCV2a(19.35％),one was PCV2b(3.23％)and one was PCV2c(3.23％).The results of amino acid sequence comparison showed that the mutation sites mainly concentrated on amino acids at positions 40-68 and 180-209.The total positive rate of pig farm sam-ples was 37.42％(119/318),and the positive rate of pig samples from different types of pig houses was 60.71％(34/56),45.83％(11/24),35.09％(20/57),and 33.33(3/9)in order from high to low.The positive rate of environmental samples from high to low was 56.36％(31/55)in feeding system,46.67％(7/15)in feces system,12.50(1/8)in decontamination area,11.11％(2/18)in living area,and no PCV2 was detected in ventilation system.The highest positive rate was 45.00％(9/20)for the tools in the house,7.14％(1/14)for the surface and sole of the clothes after leaving the house,and no PCV2 was detected on the surface and sole of the clothes before entering the house.In this study,the epidemiological investigation of PCV2 in Henan Province and its distribu-tion in swine farms were carried out,and the main circulating strains,seasons,regions and gene mutations of PCV2 in H enan Province were identified.The distribution and transmission routes of PCV2 in positive pig farms were preliminarily analyzed and summarized,which provided data basis and reference for effective prevention and control of PCV and the establishment of accurate bio-safety prevention and control measures.

The receptors of Newcastle disease virus(NDV)are sialic acid receptors that mainly in-clude neu5ac-α-2,3gal-β-1,4Glc(SAα2,3Gal)and neu5ac-2-s-α-2,6Gal10Me(SAα2,6Gal).The distribution and abundance of the two receptors in host cells have important effects on virus sus-ceptibility and intracellular proliferation.In order to further explore the effects of sialic acid recep-tors on susceptibility and proliferation characteristics of NDV different strains,the expression lev-els of SAα2,3Gal and SAα2,6Gal receptors on BHK-21 cell membrane were adjusted by overex-pression and RNAi assays,and the TCID50 values were determined after different BHK-21 cells were inoculated with NDV strains Ⅰ and LaSota.The results suggested that NDV strain LaSota preferentially binds to SAα2,6Gal and strain Ⅰ selectively binds to SAα2,3Gal receptor.Further-more,the viral titers of NDV strains LaSota and Ⅰ in cell culture were positively correlated with the expression levels of SAα2,6Gal and SAα2,3Gal receptors on host cell membrane respectively.In conclusion,our studies provide an understanding of the relationship between infectivity of NDV different strains and receptor types of host cell,and provide a method to increase viral titer of NDV for cell-based vaccine production.