Background: Malignant pleural effusion (MPE), a common complication of advanced cancers, is associated with poor prognosis and reduced quality of life. Although host–tumor interactions are known to drive MPE development, the associated immune dynamics during disease progression remain unclear. Using a Lewis lung carcinoma-induced MPE model in C57BL/6JNidfc mice, we systematically evaluated general parameters and immune cell changes at two-day intervals throughout disease progression. Results: The day of Lewis lung carcinoma cell injection into the pleural space was designated as day 0. By day 10 post-injection (p.i.), MPE-bearing mice exhibited ~ 10% body weight loss, marking the experimental endpoint. Pleural tumor mass and pleural effusion volume were minimal up to day 4 p.i. but increased sharply from day 6 onward.CD45⁺ immune cell counts rose over time, and days 6, 8, and 10 p.i. marked key stages of MPE progression. On day 6, B cells, T cells, and natural killer cells, but not macrophages and neutrophils, increased significantly compared to earlier timepoints. By day 8, all immune cell subsets except T cells exceeded day 6 levels, and at day 10, natural killer cell numbers declined while others continued to increase. Besides, the numbers of CD8⁺ T cells, Th1 cells, regulatory T cells, and M2 macrophages progressively increased from day 6 to 10. Based on these data, days 6 and 10 were defined as early and advanced MPE stages, respectively, with distinct immune phenotypes. In advanced MPE, CD8⁺ T cells displayed reduced IFN-γ, TNF-α, Granzyme B, Perforin, FasL, and Ki-67, but upregulated PD-1 and CTLA-4 relative to early stage. Similarly, Th1 cells showed decreased IFN-γ, TNF-α, and IL-2 production along with reduced Ki-67 expression. Advanced-stage M2 macrophages exhibited lower MHC-II levels and impaired phagocytosis, but higher PD-L1 and IL-10 production, while neutrophils showed reduced TNF-α release and phagocytic activity. Conclusions Our findings characterize the temporal immune dynamics associated with MPE progression in a mouse model, revealing a transition from an early immunostimulatory state to a late immunosuppressive state. This study enhances our understanding of MPE immunopathogenesis and provides a foundation for developing precise, stagespecific therapeutic strategies.

Background: and Purpose In patients with large vessel occlusion (LVO), intravenous thrombolysis (IVT) frequently alters thrombus location; however, the clinical impact of this phenomenon remains unclear. We aimed to compare post-IVT thrombus dynamics between tenecteplase and alteplase and to evaluate the association between thrombus dynamics and 3-month outcomes. Methods: This retrospective study analyzed prospectively collected, multicenter data from consecutive patients with LVO who underwent bridging therapy between January 2022 and December 2024. Thrombus dynamics were classified as resolution, migration, or stability. Analyses incorporated propensity score matching with weighting to balance baseline characteristics. Results: Of the 806 initially included patients, 746 were included after matching (373 treated with tenecteplase and 373 treated with alteplase). The incidence of thrombus migration was significantly higher in the tenecteplase group than in the alteplase group (19.3% vs. 11.3%; odds ratio [OR]: 1.92; 95% confidence interval [CI] 1.27–2.91). The advantage of tenecteplase over alteplase was restricted to patients with an IVT-to-puncture time of <60 minutes (18.6% vs. 6.2%; p=0.001) and was no longer significant when the interval ≥60 minutes (19.7% vs. 15.0%; p=0.204; pinteraction=0.043). Additionally, thrombus migration was associated with a better functional outcome (OR: 1.62; 95% CI 1.04–2.53). Finally, tenecteplase was associated with improved functional independence compared with alteplase (OR: 1.43; 95% CI 1.04–1.95). Conclusions Tenecteplase demonstrated superior efficacy in inducing thrombus migration compared with alteplase, particularly within 60 minutes of IVT administration. Thrombus migration independently predicted improved functional independence. These findings support the preferential use of tenecteplase for bridging therapy in patients with LVO.

Objective: : Acoustic neuromas, or vestibular schwannomas, pose significant surgical challenges due to their proximity to critical cranial nerves, particularly the facial nerve. The primary goal in their surgical treatment is to achieve maximal tumor removal while preserving neurological function. Recent advancements in surgical technology have introduced neuroendoscopy as an adjunctive tool that can enhance visualization during surgery. This study aimed to evaluate the efficacy of integrating neuroendoscopy with intraoperative electrophysiological monitoring in near-total resection surgeries for acoustic neuroma. Methods: : We conducted a retrospective cohort study comparing 71 patients who underwent neuroendoscopy-assisted microsurgery technique with 68 patients who received standard care group technique. Both groups underwent the suboccipital retrosigmoid sinus approach for tumor resection with intraoperative electrophysiological monitoring. Surgical outcomes, including residual tumor size, facial nerve function, audiological outcomes, and complication rates, were compared between the two groups. Results: : The neuroendoscopy-assisted group demonstrated a significantly smaller residual tumor size, improved immediate and 1-year postoperative House-Brackmann grades, and a higher facial nerve preservation rate compared to the standard care group (p<0.05). There was no significant difference in operation time, blood loss, cerebrospinal fluid leakage, or complication rates between the groups. Word recognition scores after a year were significantly higher in the neuroendoscopy-assisted group (p<0.05). Conclusion : The integration of neuroendoscopy-assisted microsurgery technique in acoustic neuroma surgery improves facial nerve function and residual tumor size without increasing surgical complications. These findings support the utility of this combined approach in enhancing surgical outcomes for patients with acoustic neuroma.

OBJECTIVE To explore the mecha nism by which Liuwei dihuang pill promotes tendon-bone healing by regulating the interaction between bone marrow mesenchymal stem cells （BMSCs） and macrophages through Wnt/ β -catenin pathway. METHODS BMSCs were co-cultured with macrophages at a ratio of 1∶4 and divided into control group， 10% drug-containing serum group， 20% drug-containing serum group， Wnt/ β -catenin pathway inhibitor Dickkopf-related protein 1 （DKK-1） group， and 20% drug-containing serum+DKK-1 group. After 48 hours of cell co-culture and 14 days of osteogenic induction， the CD86 and CD206 positive cell rates in macrophages， the proportion of calcium nodule positive staining area in BMSCs， the levels of osteocalcin （OCN） and oncostatin M （OSM） and alkaline phosphatase （ALP） activity in cell supernatant， as well as the mRNA and protein expression levels of OCN， Runt-related transcription factor 2 （RUNX2）， OSM， low-density lipoprotein receptor-related protein 5 （LRP5）， β -catenin in cells were detected. Pearson correlation analysis was performed to assess the correlation between LRP5 and β -catenin protein expression with OCN， RUNX2， OSM protein expression， and CD206 positive cell rate， respectively. RESULTS Compared with the control group， the CD86 positive cell rates in the 10% drug-containing serum group and the 20% drug-containing serum group were significantly reduced， while the CD206 positive cell rate， proportion of calcium nodule positive staining area， OCN level， OSM level， ALP activity， and mRNA and protein expression levels of OCN， RUNX2， OSM， LRP5， β -catenin were significantly increased （ P ＜0.05）. Compared with the 20% drug-containing serum group， the changes in the above indicators in the 20% drug-containing serum+DKK-1 group were significantly reversed （ P ＜0.05）. The protein expression of LRP5 and β -catenin was positively correlated with the pro tein expression of OCN， RUNX2， OSM， and CD206 positive cell rate. CONCLUSIONS Liuwei dihuang pill can activate the Wnt/ β -catenin pathway， induce M2 polarization of macrophages and secretion of OSM， promote osteogenic differentiation and matrix mineralization of BMSCs， and synergistically promote tendon-bone healing.

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 explore the mecha nism by which Liuwei dihuang pill promotes tendon-bone healing by regulating the interaction between bone marrow mesenchymal stem cells （BMSCs） and macrophages through Wnt/ β -catenin pathway. METHODS BMSCs were co-cultured with macrophages at a ratio of 1∶4 and divided into control group， 10% drug-containing serum group， 20% drug-containing serum group， Wnt/ β -catenin pathway inhibitor Dickkopf-related protein 1 （DKK-1） group， and 20% drug-containing serum+DKK-1 group. After 48 hours of cell co-culture and 14 days of osteogenic induction， the CD86 and CD206 positive cell rates in macrophages， the proportion of calcium nodule positive staining area in BMSCs， the levels of osteocalcin （OCN） and oncostatin M （OSM） and alkaline phosphatase （ALP） activity in cell supernatant， as well as the mRNA and protein expression levels of OCN， Runt-related transcription factor 2 （RUNX2）， OSM， low-density lipoprotein receptor-related protein 5 （LRP5）， β -catenin in cells were detected. Pearson correlation analysis was performed to assess the correlation between LRP5 and β -catenin protein expression with OCN， RUNX2， OSM protein expression， and CD206 positive cell rate， respectively. RESULTS Compared with the control group， the CD86 positive cell rates in the 10% drug-containing serum group and the 20% drug-containing serum group were significantly reduced， while the CD206 positive cell rate， proportion of calcium nodule positive staining area， OCN level， OSM level， ALP activity， and mRNA and protein expression levels of OCN， RUNX2， OSM， LRP5， β -catenin were significantly increased （ P ＜0.05）. Compared with the 20% drug-containing serum group， the changes in the above indicators in the 20% drug-containing serum+DKK-1 group were significantly reversed （ P ＜0.05）. The protein expression of LRP5 and β -catenin was positively correlated with the pro tein expression of OCN， RUNX2， OSM， and CD206 positive cell rate. CONCLUSIONS Liuwei dihuang pill can activate the Wnt/ β -catenin pathway， induce M2 polarization of macrophages and secretion of OSM， promote osteogenic differentiation and matrix mineralization of BMSCs， and synergistically promote tendon-bone healing.

To achieve rapid and visual detection of Plasmodium vivax,a detection method based on recombinase polymerase amplification(RPA)technology and lateral flow dipstick(LFD)was established and evaluated.Targeting the conserved sequence of the P.vivax 18S rRNA gene(GenBank:DQ660817.1)as the target sequence,primers and probes were designed with Primer Premier 5,and the P.vivax recombinant plasmid(pUCPv)was constructed as the standard.A sensitive and specific RPA-LFD-based rapid visual detection method for P.vivax nucleic acids was established.The plasmid standard was serially diluted 10-fold to concentrations of 1×103,1×102,1×101,1×10?,and 1×10?1 copies/μL for sensitivity testing.To evaluate specificity,whole blood DNA samples from patients infected with Plasmodium falciparum,Plasmodium malariae,Plasmodium ovale,or Leishmania donovani,as well as healthy participants,were tested by RPA-LFD.Additionally,The assay′s accuracy was evaluated by testing whole blood DNA samples from 24 confirmed P.vivax-infected patients.This study successfully established a sensitive,specific,and rapid visual RPA-LFD method for detecting P.vivax nucleic acids.The assay can complete P.vivax detection within 20 minutes under isothermal conditions at 39 ℃,achieving a sensitivity of 1 copy/μL.There is no significant cross reaction with parasites such as other Plasmodium species and L.donovani,and the specificity is 100%.All 24 DNA samples from confirmed P.vivax patients were detected,showing a 100%detection rate.The developed RPA-LFD assay exhibits excellent sensitivity and specificity,requires only simple heating equipment,and is user-friendly.This rapid visual detection method is particularly suitable for P.vivax screening in low-resource settings.

Aim To investigate the impact of G pro-tein-coupled estrogen receptor 1(GPER1),also known as GPR30 playing a significant role in the nerv-ous system,on neuronal damage and cognitive dysfunc-tion following epileptic seizures.Methods The pro-tein expression levels of GPER1 and the DNA damage marker γ-H2AX in epileptic rats were assessed using Western blot.The hippocampal neuronal damage and apoptosis in pilocarpine-induced epilepsy models were evaluated using Nissl and TUNEL staining techniques,compared with GPER1 knockdown(GPER1-KD)rats with wild-type(WT)controls.The behavioral activi-ties,including memory and spatial learning,were mo-nitored during the chronic phase of epilepsy using the IntelliCage system.Results Compared to the control group,GPER1 protein expression in the cerebral cortex and hippocampus significantly increased 24 hours post-epilepsy onset.In the GPER1-KD+EP group,hipp-ocampal neuronal damage was more severe,with a sig-nificant increase in apoptotic neurons compared to the WT+EP group.The IntelliCage data revealed that during free exploration,nose contact,position learn-ing,and reverse position learning stages in the GPER1-KD+EP group exhibited fewer visits and a higher error rate than in the WT+EP group.Conclu-sions Deficiency in GPER1 impairs memory and spa-tial learning abilities following epilepsy,potentially due to exacerbated neuronal injury,apoptosis,and inflam-mation.GPER1 represents a promising therapeutic tar-get for mitigating post-epileptic nerve damage and cog-nitive impairment.

Objective:To systematically evaluate the current status of research on the development of indicators for entrustable professional activities (EPAs) of residents in China.Methods:We searched the China National Knowledge Infrastructure, Wanfang Data, Airiti Library, PubMed, Embase, and Web of Science databases for literature on the development of EPA indicators for residents in China published between January 1, 2005 and February 28, 2025. Two researchers independently screened the literature and extracted data, followed by descriptive analysis. The quality of the studies was assessed using the Joanna Briggs Institute critical appraisal tool for expert opinion. Quantitative data were presented as medians (ranges) and qualitative data were presented as frequencies (percentages).Results:A total of eight articles were included, in which two general EPA indicator systems and six specialty-specific EPA indicator systems were developed for residents. The overall quality of the research was high, with the main shortcomings related to the methods used in the process of constructing the consensus indicators. The number of experts recruited ranged from 22 to 45, with 100.00% response rate, high authority coefficients (0.820-0.914), and high coordination coefficients (0.157-0.741). Most of the studies used literature reviews as one source for the indicator pool (8 studies, 100.00%), employed the Delphi method to reach consensus (6 studies, 75.00%), and provided inclusion criteria for the indicators (7 studies, 87.50%). However, only one study (12.50%) explored the practical application of the developed indicators, and none of the studies set indicator weights or conducted quality assessments. The number of EPA indicators developed ranged from 10 to 38 per study. The reporting of EPA indicators was included in most studies regarding titles (8 studies, 100.00%) and the expected levels of entrustment at various stages of training (6 studies, 75.00%), but the reporting on other aspects was lacking. Among the specialty-specific EPA indicators, 38.39% overlapped with the general EPAs indicators.Conclusions:The research on the development of EPA indicators for residents in China is still in its early stages, and there is room for improvement in methodological quality and reporting coverage. There is partial overlap between specialty-specific and general EPA indicators, failing to fully reflect the unique characteristics of different specialties.

Objective:To investigate the current status of Chinese-foreign cooperative education programs for medical majors, and to discuss the potential problems and development trends of this field.Methods:Related data were collected from the information platform of Chinese-Foreign Cooperation in Running Schools by Ministry of Education of the People's Republic of China, and the characteristics of Chinese-foreign cooperative education programs for medical majors were extracted for analysis. Categorical data were expressed as frequency (percentage), and continuous data were expressed as mean±standard deviation.Results:A total of 83 Chinese-foreign cooperative education programs for medical majors were included in the study, accounting for only 3.45% (83/2 406) of all programs. Chinese partners in these cooperative programs were mainly from East China (41 programs, 49.40%), while foreign partners were mainly from Europe (39 programs, 46.99%). The mean duration of these programs was (3.61±0.88) years, with an enrollment of (87.08±35.52) students. Most of the students were included in National General Higher Education Enrollment Plan (79 programs, 95.18%), and the main majors included nursing (39 programs, 46.99%), medical technology (19 programs, 22.89%), and clinical medicine (11 programs, 13.25%), with the main enrollment level of junior college (45 programs, 54.22%). Chinese partners in the cooperative programs mainly issued academic certificate (45 programs, 54.22%) or academic certificate plus degree certificate (36 programs, 43.37%), while most foreign partners did not issue such certificates (44 programs, 53.01%).Conclusions:There are several problems in Chinese-foreign cooperative education programs for medical majors, such as a limited number of programs, a significant regional difference, an imbalanced distribution of specialties, a low level of education, and inconsistency in issuance of certificates, which still requires further improvement and standardization. However, there are also high-level and high-quality programs for reference.