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.

Both type 2 diabetes mellitus (T2DM) and metabolic associated fatty liver disease (MAFLD) fall within the spectrum of metabolic diseases, and they exhibit a bi-directional causal relationship and robust reciprocal association. Their shared pathological cornerstone is insulin resistance (IR), which involves the interplay of mitochondrial dysfunction and chronic inflammation, forming a cascading pathological process of “IR-mitochondrial dysfunction-inflammation”. This largely explains the notable upward trend in T2DM-MAFLD co-occurrence observed over recent years. Exercise intervention, as a safe and effective non-pharmacological approach, can improve the pathological progression of these patients at multiple levels. Following the logical framework of “pathogenesis-efficacy comparison-molecular mechanisms-clinical translation”, this article systematically compares the efficacy and molecular mechanisms of moderate-intensity continuous training (MICT), resistance exercise, high-intensity interval training (HIIT), and combined training. MICT reduces intrahepatic triglycerides by promoting lipolysis and improving cardiorespiratory fitness; resistance exercise increases muscle mass and basal metabolic rate, offering unique advantages in preserving muscle while reducing fat and improving insulin sensitivity; HIIT is a time-efficient exercise modality that enhances patients’ cardiorespiratory fitness and insulin sensitivity by alternating brief periods of vigorous exertion with recovery periods, with a prominent short-term triglyceride-lowering effect; combined training produces synergistic effects, comprehensively improving glucolipid metabolism and showing the best long-term adherence. Mechanistically, exercise exerts its beneficial effects through three common pathways: (1) AMPK-mediated lipid oxidation and mitochondrial biogenesis; (2) IRS/PI3K/Akt-mediated insulin signaling sensitization; and (3) Nrf2/ARE anti-oxidation and TGF-β/Smads anti-fibrosis regulation. Different exercise modalities activate these pathways with distinct emphases: MICT most directly and persistently activates the AMPK pathway; resistance exercise uniquely improves IRS/PI3K/Akt signaling through muscle mass gain; HIIT induces the highest AMPK activation intensity and triggers unique lactate-mediated signaling regulation; combined training integrates the above multiple mechanistic advantages. For clinical translation, multidisciplinary team collaboration is essential to ensure safety and adherence. Individualized prescriptions should be formulated according to the FITT-VP principle and patient phenotypes—frequency of 3-5 sessions/week of aerobic exercise combined with 2-3 sessions/week of resistance exercise; intensity of moderate-intensity (40%-60% heart rate reserve (HRR))aerobic exercise and 60%-80% of one-repetition maximum (1-RM) for resistance exercise; time of at least 150 min/week of moderate-intensity aerobic exercise, 30-60 min per session; type of combined training as the preferred modality; total volume of≥500-1 000 MET-min/week; and progression adjusted every 4-6 weeks—with real-time adjustments supported by wearable devices, ultimately forming a closed-loop management system from initial assessment to long-term follow-up. Notably, current studies have limitations such as small sample sizes and short intervention periods. Future research should focus on long-term follow-up, multi-omics biomarkers, and combined exercise-drug strategies. In conclusion, the systematic integration of structured, individualized, and sustainable exercise interventions into the multidisciplinary management pathway for patients with T2DM complicated by MAFLD is an urgent need in current clinical practice.

Enzymatic cascade catalysis has emerged as an effective means to enhance the sensitivity of biosensors due to its remarkable amplification effect on electrochemical signals.However,the most used natural enzymes have high specificity and high catalytic activity,but are susceptible to environmental factors,easy denaturation and inactivation,and high cost,which limit their practical applications.Additionally,the majority of nanozymes with excellent catalytic activity cannot be directly used as redox probes.The redox signal can only be required under high potentials in strong acid/alkali solutions,or functionalized with electroactive substances.To tackle this problem,herein,AuNPs(glucose oxidase-like activity)and Mn,Zr dual-doped CeO2 nanozymes(Mn,Zr-CeO2,peroxidase-like activity)were used as model enzymes to construct a high-performance nanozymes cascade catalytic system.Owing to high Ce4+/Ce3+ratio and a considerable number of oxygen vacancies,Mn,Zr-CeO2 nanozymes exhibited excellent peroxidase-like activity and could generate amplified electrochemical signals in neutral medium at low potentials.Furthermore,the porous structure of Mn,Zr-CeO2 nanozymes could accelerate the mass transfer of intermediate H2O2,thereby enhancing the efficiency of enzymatic cascade catalysis.As a result,a label-free electrochemical biosensor was constructed for sensitive detection of the cancer marker miRNA-21 at physiological pH,with a detection limit as low as 32.5 fmol/L.This strategy offered a novel approach for the development of a new generation of high-performance nanozymes cascade platforms,which could be widely applied in the fields such as biotechnology,bioanalysis,and disease diagnosis.

Objective:To explore the relationship between peripheral blood microRNA-29b (miR-29b), fibroblast growth factor 23 (FGF23), adiponectin (ADP) and disease progression as well as bone metabolism disorders in patients with chronic kidney disease (CKD).Methods:A total of 106 CKD patients diagnosed in the Department of Nephrology, the First People′s Hospital of Hefei from February 2022 to February 2024 were selected as the CKD group, and 103 healthy subjects who underwent physical examination during the same period were selected as the control group. Differences in peripheral blood miR-29b, ADP, FGF23, serum calcium, serum phosphorus, alkaline phosphatase (ALP), 25-hydroxyvitamin D, and renal function levels between the two groups were compared. The CKD group was stratified according to CKD stages, and the above indicators were compared. Simple linear correlation analysis was used to analyze the correlation between miR-29b, ADP, FGF23 and bone metabolism indicators.Results:The levels of peripheral blood ADP and FGF23 in the CKD group were higher than those in the control group, while the level of miR-29b was lower, with statistically significant differences (all P<0.05). The levels of serum phosphorus, ALP, serum creatinine, and 24-hour urinary protein in the CKD group were higher than those in the control group, while the levels of serum calcium and 25-hydroxyvitamin D were lower, with statistically significant differences (all P<0.05). Among the 106 CKD patients, there were 8 cases in CKD stage 1, 22 in stage 2, 38 in stage 3, 32 in stage 4, and 6 in stage 5. The levels of peripheral blood ADP and FGF23 in patients with CKD stages 4-5 were higher than those in patients with CKD stages 1-3, while the level of miR-29b was lower, with statistically significant differences (all P<0.05). The levels of serum phosphorus, ALP, serum creatinine, and 24-hour urinary protein in patients with CKD stages 4-5 were higher than those in patients with CKD stages 1-3, while the levels of serum calcium and 25-hydroxyvitamin D were lower, with statistically significant differences (all P<0.05). In CKD patients, peripheral blood miR-29b was positively correlated with serum calcium and 25-hydroxyvitamin D (all P<0.05), and negatively correlated with ALP ( P<0.05). Peripheral blood ADP in CKD patients was negatively correlated with serum calcium ( P<0.05) and positively correlated with ALP ( P<0.05). Peripheral blood FGF23 in CKD patients was negatively correlated with serum calcium ( P<0.05) and positively correlated with ALP ( P<0.05). Conclusions:The levels of peripheral blood ADP and FGF23 in CKD patients are significantly increased, and the level of miR-29b is significantly decreased, which are related to disease progression and bone metabolism disorders in CKD patients.

Objective:To evaluate the feasibility and efficacy of our self-designed intelligent robot-assisted reduction system for fresh subtrochanteric fractures of the femur.Methods:A retrospective cohort study was conducted to include 10 patients with fresh subtrochanteric fracture of the femur who had been admitted to Department of Orthopedic Trauma, Beijing Jishuitan Hospital from January 2024 to July 2024. There were 7 males and 3 females with an age of (45.0±14.3) years and an interval from injury to surgery of (7.9±3.7) d. All the patients were treated by minimally invasive reduction which was assisted by our self-designed intelligent robot, and internal fixation with intramedullary nails. The operation duration, intraoperative reduction duration, intraoperative blood loss, and intraoperative fluoroscopy frequency were recorded. The reduction effect was evaluated by calculating the differences between preoperative planning and postoperative CT reconstruction (i.e., the differences in femoral shaft length and in rotation angle). The hip functional recovery was assessed by Harris hip function Scoring.Results:The mean operation time was 200.0 (161.3, 217.5) min, the reduction time (83.0±35.5) min, the intraoperative blood loss (290.0±110.1) mL, and the intraoperative fluoroscopy 18.5 (9.0, 19.3) times. In all patients, the difference in femoral shaft length was (2.4±1.4) mm, and the difference in rotation angle 5.1°±3.0°. All patients were followed up for (8.2±2.0)months. All the fractures got united at the last follow-up. Their Harris hip function score was (83.3±4.1) points.Conclusion:Our self-designed intelligent robot-assisted reduction system is feasible and effective in the surgery of fresh subtrochanteric fracture of the femur, because the robot system can complete the autonomous planning of reduction approaches before surgery and assist fracture reduction under real-time monitoring with three-dimensional images, leading to fine outcomes.

Objective To analyze the implementation effect of medical risk early warning monitoring based on closed-loop complaint management.Methods A total of 453 patients admitted to the Second People's Hospital of Guizhou Province from January 2022 to December 2023 were selected retrospectively.Among them,222 patients admitted to the departments where the medical risk early warning monitoring system based on closed-loop complaint management was implemented were included in the observation group.231 patients admitted to the departments where routine medical care and complaint management were implemented were included in the control group.Risk events,complaints,medical service quality and patient satisfaction were compared between the two groups.Results The incidence rates of pressure ulcers,phlebitis,falls and other risk events were lower in the observation group than in the control group(P＜0.05),the complaint rates of examination departments and auxiliary departments and total were lower in the observation group than in the control group(P＜0.05),the complaint rates of service attitude,communication problems and medical dispute were lower in the observation group than in the control group(P＜0.05),the satisfaction rate of the observation group was higher than that of the control group(P＜0.05),the observation group had higher scores than the control group in terms of health education,communication and notification,coping capacity,specialist skills,basic skills,infection prevention and total(P＜0.05).Conclusion The medical risk early warning monitoring system based on closed-loop complaint management can reduce risk events and complaints,and improve medical service quality and satisfaction,it can achieve significant effects in practice.

ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled， and according to the presence or absence of esophageal and gastric varices under gastroscopy， they were divided into esophageal and gastric varices group （GOV group） and non-esophageal and gastric varices group （NGOV group）. Related data were collected， including age， sex， imaging findings， and laboratory markers. The chi-square test was used for comparison of categorical data between groups； the least significant difference t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the diagnostic value of five scoring models， i.e.， fibrosis-4 （FIB-4）， LOK index， LPRI， aspartate aminotransferase-to-platelet ratio index （APRI）， and aspartate aminotransferase/alanine aminotransferase ratio （AAR）. The binary logistic regression method was used to establish a combined model， and the area under the ROC curve （AUC） was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group， the GOV group had a significantly higher age （52.64±1.44 years vs 47.96±1.68 years， t=0.453， P<0.05） and significantly lower levels of alanine aminotransferase ［42.00 （24.00 — 17.00） U/L vs 82.00 （46.00 — 271.00） U/L， Z=-3.065， P<0.05］， aspartate aminotransferase ［44.00 （32.00 — 96.00） U/L vs 62.00 （42.50 — 154.50） U/L，Z=-2.351， P<0.05］， and platelet count ［100.00 （69.00 — 120.00）×10⁹/L vs 119.00 （108.50 — 140.50）×10⁹/L， Z=-3.667， P<0.05］. The ROC curve analysis showed that FIB-4， LOK index， LPRI， and AAR used alone had an accuracy of 0.667， 0.681， 0.730， and 0.639， respectively， in the diagnosis of esophageal and gastric varices （all P<0.05）， and the positive diagnostic rates of GOV were 69.97%， 65.28%， 67.33%， and 58.86%， respectively， with no significant differences in AUC values （all P>0.05）， while APRI used alone had no diagnostic value （P>0.05）. A combined model （LAF） was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%， with a significantly higher AUC than FIB-4， LOK index， LPRI， and AAR used alone （Z=-2.773，-2.479，-2.206， and-2.672， all P<0.05）. ConclusionFIB-4， LOK index， LPRI， and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy， which provides a certain reference for clinical promotion and application.

Objective To analyze the implementation effect of medical risk early warning monitoring based on closed-loop complaint management.Methods A total of 453 patients admitted to the Second People's Hospital of Guizhou Province from January 2022 to December 2023 were selected retrospectively.Among them,222 patients admitted to the departments where the medical risk early warning monitoring system based on closed-loop complaint management was implemented were included in the observation group.231 patients admitted to the departments where routine medical care and complaint management were implemented were included in the control group.Risk events,complaints,medical service quality and patient satisfaction were compared between the two groups.Results The incidence rates of pressure ulcers,phlebitis,falls and other risk events were lower in the observation group than in the control group(P＜0.05),the complaint rates of examination departments and auxiliary departments and total were lower in the observation group than in the control group(P＜0.05),the complaint rates of service attitude,communication problems and medical dispute were lower in the observation group than in the control group(P＜0.05),the satisfaction rate of the observation group was higher than that of the control group(P＜0.05),the observation group had higher scores than the control group in terms of health education,communication and notification,coping capacity,specialist skills,basic skills,infection prevention and total(P＜0.05).Conclusion The medical risk early warning monitoring system based on closed-loop complaint management can reduce risk events and complaints,and improve medical service quality and satisfaction,it can achieve significant effects in practice.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Objective To investigate the anatomical and microscopic structures of interstitial fluid flow channels in the skin tissue of hand dorsum in human cadavers.Methods Totally 7 fresh cadavers within 12 hours post-mortem were included.MRI was used to observe the distribution of interstitial fluid flow from the first phalanx of the fingers to the wrist,precisely locating the flow channels.Based on imaging results,histological analyses were conducted to determine the histological characteristics of the flow channels.Furthermore,multi-immunofluorescence and microcomputed tomography(Micro-CT)techniques were employed to analyze the channels,and image post-processing was used to elucidate their anatomical structures at the microscopic level.Results After injecting a contrast agent into the first phalanx of ten finger specimens and applying repeated pressure,MRI image revealed centripetal long-range interstitial fluid flow along channels distinct from blood vessels and lymphatic vessels.Histological analysis and Micro-CT further confirmed that the flow primarily occurred within the fibrous connective tissue and adventitia of the skin.Conclusion The orderly fibrous connective tissue and adventitia in the skin form the interstitial fluid flow channels in the human hand dorsum skin,named as"stromal membrane channels"in the skin.