Stroke is one of the leading causes of disability and mortality worldwide. Research into its mechanisms and the development of therapeutic strategies heavily rely on animal models that accurately replicate the pathological features of human disease. An ideal animal model for stroke should not only reproduce the neurological deficits and pathological changes observed in clinical patients but also demonstrate good reproducibility and translational value. This review focuses on the preparation and evaluation methods of ischemic stroke animal models. Firstly, it elaborates on the selection criteria, advantages, and disadvantages of experimental animals, including rodents (rats, mice) and non-rodents (non-human primates, miniature pigs, rabbits, zebrafish). Secondly, it provides a detailed overview of the modeling principles, key procedures, and application scopes for ischemic stroke models and hemorrhagic stroke models. Furthermore, the review summarizes advances in the applications of emerging technologies—including gene editing [e.g., clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing], multimodal imaging (e.g., two-photon microscopy, photoacoustic imaging), artificial intelligence, optogenetics, 3D bioprinting, organoid models, and multi-omics–in model optimization, precise assessment, and mechanistic investigation. Finally, based on a systematic analysis of relevant domestic and international literature from 2019 to 2024, this review discusses model selection strategies based on research objectives, a multidimensional evaluation system encompassing behavioral, imaging, and molecular pathological assessments, and envisions future directions involving technological integration to achieve model precision and individualization. This article aims to provide a comprehensive methodological reference to help researchers select appropriate animal models of stroke according to specific scientific questions.

ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

Objective To construct and evaluate a prognostic model for clear cell renal cell carcinoma(ccRCC)based on preoperative lipid ratios, cM0(i+)staging, and other clinical characteristics, so as to provide a precise tool for clinical prognosis assessment. Methods A retrospective analysis was conducted on the clinical data of 215 ccRCC patients treated in our hospital during May 2014 and May 2023. Lipid ratios were calculated using preoperative lipid data, and patients were divided into cM0(i+)stage or cM0 stage according to postoperative circulating tumor cells(CTCs)test results. The optimal lipid ratio and cutoff value were selected using receiver operating characteristic(ROC)curves and the X-tile method. Patients were subdivided into three groups based on the level of the low-density lipoprotein cholesterol to non-low-density lipoprotein cholesterol ratio(LNLR)and cM0(i+)staging:Group A [LNLR＞1.68 and diagnosed with cM0(i+)], Group B [LNLR＞1.68 or diagnosed with cM0(i+)], and Group C(LNLR ≤1.68 and diagnosed with cM0). Kaplan-Meier survival analysis was used to plot survival curves for patients in different groups. The log-rank test was employed to compare differences in recurrence-free survival(RFS)among the subgroups. Multivariate Cox regression analysis was conducted to identify the independent risk factors influencing RFS, and a nomogram prediction model was constructed based on these results. The predictive performance of the model was validated using ROC curves, calibration curves, and decision curves. Results ROC curves were plotted for lipid markers, and LNLR was identified as the most predictive for RFS. Its optimal cutoff point was 1. 68. Patients in Group A experienced a significantly shorter postoperative RFS. Multivariate Cox regression analysis identified preoperative LNLR, cM0(i+)staging, pathological grade, and stage as independent risk factors for RFS. A nomogram model was constructed based on these risk factors. The area under the ROC curve(AUC)for 1-, 3-, and 5-year RFS was 0.896(95% CI:0.8121-0.9627), 0.890(95%CI:0.7879-0.9641), and 0.870(95%CI:0.7697-0.9526), indicating good discriminatory ability and predictive performance. Calibration plots demonstrated good agreement between predicted and actual outcomes. Clinical decision curve analysis showed high clinical net benefit. Conclusion Preoperative LNLR level is an independent risk factor for RFS in ccRCC patients. The prognostic prediction model based on LNLR, cM0(i+)staging, patient pathological grade, and staging demonstrates good predictive performance for RFS and holds potential clinical application value.

Objective To address the need for rapid review of automated organ-at-risk (OAR) contouring for head-and-neck cancer in online adaptive radiotherapy, this study used dosimetric indices as the reference standard to evaluate the suitability of geometric similarity metrics and to develop a rapid screening model that balances the risk of missed errors with review efficiency. Methods This retrospective study included 29 patients with head-and-neck radiotherapy, yielding 243 pairs of OAR contours (auto-generated vs. manual). Geometric similarity metrics, including the Dice similarity coefficient (Dice), the 95th percentile Hausdorff distance (HD95), and the maximum Hausdorff distance (HD100), were computed between the two contour sets. Using the dose distributions from clinical treatment plans, dosimetric differences between the two contour sets were calculated for key indices, including mean dose (D_mean) and maximum dose (D_max). Correlations between geometric metrics and dosimetric differences were analyzed. Dosimetric discrepancy events were defined as Y_3Gy using a threshold of 3 Gy. Within a univariable logistic regression triage framework, each geometric metric was used as an independent variable to estimate the probability of Y_3Gy. Discriminative performance was assessed using receiver operating characteristic (ROC) curves and precision-recall (PR) curves, with the area under the curve (AUC) including ROC-AUC and PR-AUC. Practical operating thresholds were determined via threshold sweeping. Results Geometric similarity metrics showed weak-to-moderate correlations with dosimetric differences; compared with maximum dose, correlations with mean dose differences were more consistent. Among the evaluated metrics, HD95 achieved the best classification performance for Y_3Gy. Threshold sweeping suggested that an HD95 threshold in the range of 4-9 mm can balance the risk of missed discrepancies with the efficiency of automated contour quality assurance (QA). Conclusion Several geometric similarity metrics demonstrated only weak-to-moderate associations with dosimetric differences. For head-and-neck OAR contour QA in this study, HD95 provided the best discriminative performance and can support rapid triage of automated contours, with a practical operating threshold range of 4-9 mm, potentially improving the efficiency of adaptive radiotherapy workflows.

Objective To address the need for rapid review of automated organ-at-risk (OAR) contouring for head-and-neck cancer in online adaptive radiotherapy, this study used dosimetric indices as the reference standard to evaluate the suitability of geometric similarity metrics and to develop a rapid screening model that balances the risk of missed errors with review efficiency. Methods This retrospective study included 29 patients with head-and-neck radiotherapy, yielding 243 pairs of OAR contours (auto-generated vs. manual). Geometric similarity metrics, including the Dice similarity coefficient (Dice), the 95th percentile Hausdorff distance (HD95), and the maximum Hausdorff distance (HD100), were computed between the two contour sets. Using the dose distributions from clinical treatment plans, dosimetric differences between the two contour sets were calculated for key indices, including mean dose (D_mean) and maximum dose (D_max). Correlations between geometric metrics and dosimetric differences were analyzed. Dosimetric discrepancy events were defined as Y_3Gy using a threshold of 3 Gy. Within a univariable logistic regression triage framework, each geometric metric was used as an independent variable to estimate the probability of Y_3Gy. Discriminative performance was assessed using receiver operating characteristic (ROC) curves and precision-recall (PR) curves, with the area under the curve (AUC) including ROC-AUC and PR-AUC. Practical operating thresholds were determined via threshold sweeping. Results Geometric similarity metrics showed weak-to-moderate correlations with dosimetric differences; compared with maximum dose, correlations with mean dose differences were more consistent. Among the evaluated metrics, HD95 achieved the best classification performance for Y_3Gy. Threshold sweeping suggested that an HD95 threshold in the range of 4-9 mm can balance the risk of missed discrepancies with the efficiency of automated contour quality assurance (QA). Conclusion Several geometric similarity metrics demonstrated only weak-to-moderate associations with dosimetric differences. For head-and-neck OAR contour QA in this study, HD95 provided the best discriminative performance and can support rapid triage of automated contours, with a practical operating threshold range of 4-9 mm, potentially improving the efficiency of adaptive radiotherapy workflows.

Objective To address the need for rapid review of automated organ-at-risk (OAR) contouring for head-and-neck cancer in online adaptive radiotherapy, this study used dosimetric indices as the reference standard to evaluate the suitability of geometric similarity metrics and to develop a rapid screening model that balances the risk of missed errors with review efficiency. Methods This retrospective study included 29 patients with head-and-neck radiotherapy, yielding 243 pairs of OAR contours (auto-generated vs. manual). Geometric similarity metrics, including the Dice similarity coefficient (Dice), the 95th percentile Hausdorff distance (HD95), and the maximum Hausdorff distance (HD100), were computed between the two contour sets. Using the dose distributions from clinical treatment plans, dosimetric differences between the two contour sets were calculated for key indices, including mean dose (D_mean) and maximum dose (D_max). Correlations between geometric metrics and dosimetric differences were analyzed. Dosimetric discrepancy events were defined as Y_3Gy using a threshold of 3 Gy. Within a univariable logistic regression triage framework, each geometric metric was used as an independent variable to estimate the probability of Y_3Gy. Discriminative performance was assessed using receiver operating characteristic (ROC) curves and precision-recall (PR) curves, with the area under the curve (AUC) including ROC-AUC and PR-AUC. Practical operating thresholds were determined via threshold sweeping. Results Geometric similarity metrics showed weak-to-moderate correlations with dosimetric differences; compared with maximum dose, correlations with mean dose differences were more consistent. Among the evaluated metrics, HD95 achieved the best classification performance for Y_3Gy. Threshold sweeping suggested that an HD95 threshold in the range of 4-9 mm can balance the risk of missed discrepancies with the efficiency of automated contour quality assurance (QA). Conclusion Several geometric similarity metrics demonstrated only weak-to-moderate associations with dosimetric differences. For head-and-neck OAR contour QA in this study, HD95 provided the best discriminative performance and can support rapid triage of automated contours, with a practical operating threshold range of 4-9 mm, potentially improving the efficiency of adaptive radiotherapy workflows.

Tryptophan is an essential amino acid in all animals. After being metabolized through three pathways in the body, it generates many bioactive metabolites, which affect the physiological processes of the body and provide a basis for potential therapeutic targets of diseases, especially the Kynurenine pathway. This article introduces the roles of the three metabolic pathways of tryptophan in the occurrence and development of ulcerative colitis and colitis-associated colon cancer, with particular attention to the role of the Kynurenine pathway in immune regulation and its potential contradictory effects on ulcerative colitis and colitis-associated colon cancer.

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 compare the accuracy of a Chinese large language model (LLM) and radiologists in Chinese middle level professional qualification examination of radiology, and evaluate the quality of answer reasoning provided by the Chinese LLM.Methods:In this study, 100 high-quality questions were selected using stratified random sampling to form a test set. We asked the ERNIE Bot by dialogues on the website to provide the correct answers and answer reasoning for these questions. These questions were also answered by 15 radiologists with different levels of experience. The accuracy of Chinese LLM and that of radiologists were compared. Two radiologists evaluated the quality of answer reasoning using a 5-point semi-quantitative scale.Results:The accuracy of ERNIE Bot was 60.00%, which was lower than the median (interquartile) accuracy of 67.00% (64.00%, 73.00%) for radiologists, and the difference was statistically significant ( W=2.47, P=0.013). The word count of the reasoning provided by Ernie Bot was (196.44±99.25) words, with no significant difference in word count between correct and incorrect answer reasoning, which were (211.03±107.53) words and (174.55±81.84) words, respectively ( t=1.82, P=0.072). Among the correct answers, the quality of reasoning was scored as follows: 1 point for 3 questions, 2 points for 9 questions, 3 points for 12 questions, and 4 points for 36 questions. No reasoning received a score of 5. Conclusions:Chinese LLM demonstrates a certain level of medical knowledge and clinical reasoning ability, which can assist clinical teachers in educational activities. However, it is not yet able to independently tutor residents and lacks the ability of invitational and heuristic teaching.

Objective:To compare the consistency and efficacy of ultrasound and CT in the preoperative diagnosis of cervical lymph node metastasis in patients with thyroid cancer, and to explore the clinical value of the combined application of multimodal imaging.Methods:The 119 thyroid cancer patients underwent surgical treatment from January to September 2023 in Zhongshan Hospital Affiliated to Dalian University were retrospectively analyzed. All patients underwent ultrasound and CT examinations before operation. The results of postoperative histopathology examination were taken as the gold standard, the efficacy of ultrasound and CT in preoperative diagnosis of cervical lymph node metastasis was compared.Results:A total of 1 721 cervical lymph nodes were detected in 119 patients with thyroid cancer, among which 1 378 lymph nodes were benign, and 343 lymph nodes were malignant, the rate of malignant lymph nodes was 19.93% (343/1 721). Among them, the proportion of malignant lymph nodes in area Ⅵ was the highest, 22.58% (245/1 085), followed by area Ⅲ, 21.26% (37/174). The sensitivity of CT in diagnosing cervical lymph node metastasis in patients with thyroid cancer was significantly higher than that of ultrasound diagnosis: 58.46% (38/65) vs. 38.46% (25/65), the specificity was significantly lower than that of ultrasound diagnosis: 85.19% (46/54) vs. 96.30% (52/54), and there were statistical differences ( P<0.01 and <0.05); there was no statistical difference in accuracy between CT and ultrasound ( P>0.05). Conclusions:In the preoperative diagnosis of cervical lymph node metastasis in patients with thyroid cancer by ultrasound and CT, ultrasound examination has no radiation risk, while CT examination has a higher diagnostic efficiency.