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.

Ovulatory dysfunction (OD) is one of the main causes of infertility in women of childbearing age, which not only affects their reproductive ability, but also physical and mental health. Traditional treatment strategies have limited efficacies, and the emergence of biomedicines provides a promising alternative solution via the strategies of combining engineered design with modern advanced technology. This review explores the pathophysiological characteristics and related induction mechanisms of OD, and evaluates the current cutting-edge advances in its treatments. It emphasizes the potentials of biomedicines strategies such as hydrogels, nanoparticles and extracellular vesicles in improving therapeutic precision and efficacy. By mimicking natural physiological processes, and achieving controlled drug release, these advanced drug carriers are expected to address the challenges in ovarian microenvironment reprogramming, tissue repair, and metabolic and immune regulation. Despite the promising progress, there are still challenges in terms of biomedical complexity, differences between animal models and human physiology, and the demand for intelligent drug carriers in the therapy of OD. Future researches are mainly dedicated to developing precise personalized biomedicines in OD therapy through interdisciplinary collaboration, promoting the development of reproductive regenerative medicine.

OBJECTIVES: This study aimed to explore the expression of lysosomal-associated membrane protein 5 (LAMP5) and microRNA (miR)-302a-3p in oral squamous cell carcinoma (OSCC) and their functional mechanism on the invasion and metastasis of OSCC. METHODS: The expression of LAMP5 in OSCC and its sensitivity as a prognostic indicator were analyzed on the basis of The Cancer Genome Atlas database. Western blot, quantitative reverse transcription polymerase chain reaction, and cell immunocytochemistry were used to detect the expression of LAMP5 in OSCC tissues and cells. The effect of LAMP5 on the proliferation, migration, and invasion of OSCC cells was evaluated through cell counting kit-8, immunocytochemistry, migration, and invasion assays, respectively. The miRNA targeting prediction websites were used to predict the miR that regulates LAMP5 and verify the targeted regulatory effect of miR-302a-3p on LAMP5. The effect of LAMP5 knockdown on OSCC tumor growth was evaluated in a nude mouse tumorigenesis model. RESULTS: LAMP5 was highly expressed in OSCC tissues and cells. It showed high sensitivity in the early diagnosis of OSCC. LAMP5 knockdown significantly inhibited the proliferation, migration, and invasion of OSCC cells, whereas LAMP5 overexpression increased these cell activities. The expression of LAMP5 was regulated by miR-302a-3p. In vivo, LAMP5 knockdown significantly inhibited the growth of OSCC tumor. CONCLUSIONS LAMP5 promotes the malignant progression of OSCC by enhancing the proliferation, migration, and invasion of OSCC cells. The expression of LAMP5 is negatively regulated by miR-302a-3p.
MicroRNAs/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Animals ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness ; Cell Proliferation ; Mice, Nude ; Cell Movement ; Lysosomal Membrane Proteins/genetics* ; Mice ; Cell Line, Tumor ; Neoplasm Metastasis

Kounis syndrome is an acute coronary syndrome triggered by an allergic reaction, which is clinically rare and frequently subject to misdiagnosis or missed diagnosis. This article presents a case report of a 70-year-old male patient who developed a rash, pruritus, and chest pain following colon polyp resection. Coronary angiography revealed occlusion of the left anterior descending artery, and blood flow was restored after stent implantation. However, the patient experienced recurrent symptoms accompanied by loss of consciousness. Drug skin tests confirmed positive reactions to chlorhexidine and fondaparinux sodium, leading to a diagnosis of type Ⅱ Kounis syndrome. By avoiding allergenic drugs and combining antihistamines with symptomatic treatment to correct myocardial ischemia, the patient′s clinical symptoms significantly improved, and he eventually recovered and was discharged from the hospital. This case underscores the importance of maintaining vigilance for this syndrome in patients with allergies accompanied by chest pain and promptly identifying and avoiding allergens.

The tumor microenvironment is a crucial factor in tumor occurrence and progression. The hypoxic microenvironment is widely present in tumor tissue and is a key endogenous factor accelerating tumor deterioration. The "blood stasis toxin" theory, as an emerging perspective in tumor research, is regarded as the unique "soil" in tumor progression from the perspective of traditional Chinese medicine(TCM) due to its dynamic evolution mechanism, which closely resembles the formation of the hypoxic microenvironment. Scientifically integrating TCM theories with the biological characteristics of tumors and exploring precise syndrome differentiation and treatment strategies are key to achieving comprehensive tumor prevention and control. This article focused on the hypoxic microenvironment of the tumor, elucidating its formation mechanisms and evolutionary processes and carefully analyzing the internal relationship between the "blood stasis toxin" theory and the hypoxic microenvironment. Additionally, it explored the interaction among blood stasis, toxic pathogens, and hypoxic environment and proposed micro-level prevention and treatment strategies targeting the hypoxic microenvironment based on the "blood stasis toxin" theory, aiming to provide TCM-based theoretical support and therapeutic approaches for precise regulation of the hypoxic microenvironment.
Humans ; Tumor Microenvironment/drug effects* ; Neoplasms/therapy* ; Animals ; Medicine, Chinese Traditional ; Disease Progression ; Drugs, Chinese Herbal

OBJECTIVE: To explore clinical efficacy of membrane-induced technique combined with gastrocnemius muscle flap transposition in treating traumatic osteomyelitis of the upper tibia. METHODS: A retrospective analysis was conducted on 7 patients with traumatic osteomyelitis of the upper tibia who were treated with membrane-induced technique combined with gastrocnemius muscle flap transposition from January 2022 to December 2023. Among them, there were 4 males and 3 females; aged from 29 to 57 years old; 4 patients were treated after open fracture, 2 patients were treated after closed fracture, and 1 patient was treated after scalding; the courses of disease ranges from 2 weeks to 8 years; sinus tracts were present in all patients, and the lesion range of the tibia ranged from 5 to 9 cm. The results of deep tissue bacterial culture showed that 2 patients were negative, 3 patients were staphylococcus aureus, 1 patient was methicillin-resistant staphylococcus aureus, and 1 patient was pseudomonas aeruginosa and 1 patient was klebsiella pneumoniae. After debridement, the range of bone defect ranged from 8 to 12 cm, and the cortical defect accounted for approximately 30% of the circumference. The area of soft tissue defect ranged from 8.0 cm×2.0 cm to 10.0 cm×6.0 cm. At the first stage, vancomycin-loaded/meropenem/gentamicin-loaded bone cement was implanted. The gastrocnemius muscle flap was repositioned to cover the wound surface and free skin grafting was performed. After an interval of 7 to 10 weeks, the stageⅡsurgery was performed to remove bone cement. Autologous iliac bone mixed with vancomycin/gentamicin and calcium sulfate artificial bone was transplanted, and the wound was sutured. One patient retained the original internal plants, one patient removed the internal plants and replaced them with steel plate external fixation, one patient replaced the internal plants and added steel plate external fixation, and three patients were simply fixed with steel plate external fixation. One year after operation, the recovery of knee joint and ankle joint functions was evaluated by using Hospital for Special Surgery (HSS) knee joint score and Kofoed ankle joint function score respectively. RESULTS: All patients had their wounds closed simultaneously with bone cement implantation and healed well. All patients were followed up for 12 to 17 months after operation, and satisfactory bone healing was achieved at 6 months after stageⅡsurgery. Twelve months after operation, all patients had good bone healing without obvious limping was observed when walking. At 12 months after operation HSS knee joint score ranged from 93 to 100 points, and Kofoed ankle function score ranged from 96 to 100 points. CONCLUSION For traumatic osteomyelitis of the upper tibia, a staged treatment plan combining membrane-induced technique and gastrocnemius flap transposition on the basis of thorough debridement could safely cover the wound surface, effectively control bone infection and achieve satisfactory bone healing, without adverse effects on limb function.
Humans ; Male ; Female ; Middle Aged ; Osteomyelitis/surgery* ; Adult ; Surgical Flaps ; Retrospective Studies ; Tibia/injuries* ; Muscle, Skeletal/surgery*

Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

This case report describes a 68-year-old male patient diagnosed with primary hepatocellular carcinoma (HCC). After receiving Yttrium-90 microsphere selective internal radiation therapy (⁹⁰Y-SIRT), the tumor significantly reduced in size, and tumor markers alpha fetoprotein (AFP) and abnormal prothrombin (PIVKA-Ⅱ) decreased. Postoperative pathological results showed minimal residual tumor cells, indicating that ⁹⁰Y-SIRT has good efficacy and safety in downstaging and conversion of HCC, thereby facilitating subsequent surgical resection.