1.MADS-Net: a Multi-scale Attention and Dynamic Sparse Mask Fusion Network for Electrical Impedance Tomography Image Reconstruction in Breast Screening
Cheng-Tao YU ; Jia-Hui WANG ; Song-Pei HU ; Huai-Jin CHEN ; Li DING ; Xia YE ; Jia-Feng YAO
Progress in Biochemistry and Biophysics 2026;53(9):2480-2496
ObjectiveTo address the key challenges in breast electrical impedance tomography (EIT) reconstruction including the severe ill‑posedness of the inverse problem, limited measurement information from the electrodes, low contrast of small lesions, as well as the common drawbacks of traditional reconstruction methods such as boundary blurring, low spatial resolution, and weak small-target detection capability, and to overcome the limitations of existing deep learning approaches namely low training efficiency, insufficient physical consistency, and substantial information loss during the low‑to‑high dimensional mapping process, this study proposes a multi‑scale attention and dynamic sparse mask fusion network (MADS‑Net). The proposed method aims to enhance high‑resolution reconstruction accuracy, small-lesion detectability, noise robustness, and computational efficiency in breast‑screening-oriented EIT, thereby providing a feasible solution for the application of EIT in breast functional imaging. MethodsThe proposed network adopts a strategy of “locate first, reconstruct later”. It realizes adaptive allocation of computational resources through a dynamic mask module, alleviates information loss in the low-to-high dimensional mapping process via a multi-scale attention mechanism, and embeds physical constraints to improve the physical rationality of reconstruction results. The performance of the proposed method was validated through systematic numerical simulations, agar phantom experiments, and porcine tissue experiments. Comparisons were made with mainstream methods including the Gauss-Newton algorithm, convolutional neural networks, U-Net, and Deep D-Bar. The image correlation coefficient (ICC), root mean square error (RMSE), and peak signal-to-noise ratio (PSNR) were adopted as quantitative evaluation metrics. Furthermore, lesion‑level evaluation metrics were introduced to assess the capability of different methods in reconstructing abnormal target boundaries and small‑sized target regions. ResultsExperimental results demonstrate that MADS-Net outperforms all comparison methods across all test scenarios. In numerical simulations, it achieves higher accuracy in target morphology and spatial location recovery as well as better background suppression. In agar phantom experiments, its detection and imaging reliability for small targets is significantly superior to the comparison methods. In porcine tissue experiments, the model maintains good generalization performance and can adapt to complex biological tissue imaging scenarios. Quantitative results show that MADS-Net achieves an average ICC of 0.917 6±0.048 8, an RMSE as low as0.060 6±0.031 6, and a PSNR of (23.893 9±2.685 3) dB. It successfully detects tiny targets as small as 5 mm within a 100 mm diameter sensing field, reduces the total training duration by 23.5% compared with the baseline method, and maintains stable reconstruction performance even under strong noise interference. ConclusionThe results demonstrate that MADS-Net achieves favorable EIT reconstruction performance in numerical simulations, agar phantom experiments, and porcine tissue experiments, even under common practical imaging challenges including low signal-to-noise ratio and blurred tissue boundaries. This study provides a methodological reference for further research on EIT in breast-screening-related scenarios and other medical functional imaging tasks, and also offers a low-cost, radiation-free alternative for breast lesion screening that aligns with the clinical demand for non-invasive diagnostic tools. It should be noted that real clinical breast data have not yet been used for validation in this study, and the clinical applicability of the proposed method requires further investigation. Future work will prioritize collecting multi-center real clinical breast datasets, and further optimize the model’s generalization ability to adapt to individual differences in breast tissue composition to promote its clinical application.
2.Application of Novel Environmentally Friendly Reagents in Pathological Section Preparation and Immunohistochemistry
Jieying LI ; Shujun LIANG ; Ying DING ; Shuying LIU ; Lina QIN ; Zhaoliang PAN ; Lianqiang FENG ; Huijie YUAN
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(3):509-517
ObjectiveTo explore the application effects of environmentally friendly reagents versus traditional reagents in tissue processing, paraffin sectioning, hematoxylin-eosin (HE) staining, special staining, and immunohistochemistry. MethodsPancreatic, renal, splenic, hepatic, pulmonary, skeletal muscle, and cardiac tissues were collected from mice and New Zealand rabbits, and randomly divided into a traditional group (Group A), an environmentally friendly reagent I group (Group B), and an environmentally friendly reagent Ⅱ group (Group C). The processed tissue sections from all three groups were subjected to paraffin sections, HE staining, phosphotungstic acid-hematoxylin staining, and Mallory trichrome staining. The pancreatic tissue sections were subjected to immunohistochemical detection of insulin protein. Evaluation criteria included tissue morphological integrity, embedding operability, section quality, and staining effects. ResultsNo significant differences were observed among the three groups of samples in terms of fixation efficacy, embedding operations, and section quality. After HE staining, all groups exhibited bright nuclear and cytoplasmic staining with clear contrast, with excellent-and-good rates of 98%, 99%, and 97% for Groups A, B, and C, respectively, showing no statistically significant differences (A vs. B, P=0.561; A vs. C, P=0.651). In phosphotungstic acid-hematoxylin staining, Groups A and C showed clear structural contrast and bright staining for striated muscle and collagen fibers, whereas Group B exhibited uneven staining. The excellent-and-good rates were 100%, 10%, and 95% for Groups A, B, and C, respectively, with significant differences between Group A and Group B (P<0.01) but no statistical difference between Group A and Group C (P=0.311). In Mallory trichrome staining, Groups A and B outperformed Group C. The excellent-and-good rates were 95%, 90%, and 15% for Groups A, B, and C, respectively, with significant differences between Group A and Group C (P<0.01), but no statistical difference between Group A and Group B (P=0.548). Immunohistochemical results showed that Group A had a clean background with no non-specific staining, while Groups B and C exhibited significant non-specific staining, with statistically significant differences in non-specific staining rates between the groups (A vs. B, 5% vs. 100%, P<0.01; A vs. C, 5% vs.100%, P<0.01). ConclusionIn HE staining, environmentally friendly reagents demonstrated effective tissue fixation and staining results comparable to traditional reagents, meeting the teaching requirements. For special staining, Group B and Group C performed better in Mallory trichrome staining and phosphotungstic acid-hematoxylin staining, respectively. However, environmentally friendly reagents exhibited non-specific staining issues in immunohistochemistry, where further optimization is required.
3.Effect of Wenyang Shengji Ointment (温阳生肌膏) on MGO Content and HIF-1a/VEGF Pathway in Wound Tissue of Diabetic Wound Model Rats with Yin Syndrome
Xinyu HUANG ; Li CHEN ; Yarong DING ; Jun WANG ; Shuihua FENG ; Zhongzhi ZHOU
Journal of Traditional Chinese Medicine 2025;66(4):382-389
ObjectiveTo investigate the possible mechanism of Wenyang Shengji Ointment (温阳生肌膏, WSO) in the treatment of diabetic wounds with yin syndrome. MethodsA total of 24 SD rats were randomly divided into a group (n=6) and modeling group (n=18). The modeling group rats were fed with high-fat diet for 14 days and then were injected intraperitoneally with streptozotocin to induce diabetic model. After steroid injection, full-thickness skin defects were created on the back of the rats to establish a diabetic wound with yin syndrome model. The normal group was fed with regular diet, and full-thickness skin defects were created surgically on the back of the rats. The 18 successfully modeled rats were further divided into three groups, the model group, the WSO group, and the Beifuxin (Recombinant Bovine Basic Fibroblast Growth Factor Gel, BX) group, 6 rats in each group. The WSO group was given the ointment to the wound, the Beifuxin group was givne BX gel, and the normal group and model group was disinfected and treated with saline. All groups had their dressings changed once daily for 14 days. Wound healing was recorded on days 0, 3, 7, and 14, and the wound healing rate was calculated on day 3, 7, and 14. On day 14 after treatment, HE staining was performed to observe the pathological morphology of the wound tissue. Western Blot was used to detect the relative protein levels of hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Immunofluorescence was used to measure the fluorescence intensity of HIF-1α in the wound tissue, and ELISA was used to detect the methylglyoxal (MGO) content in the wound tissue. ResultsCompared with the normal group, the model group showed poor wound healing on day 3, 7, and 14, with a low wound healing rate (P<0.01). HE staining showed scab coverage on the wound, with inflammatory cell infiltration and disorganized collagen arrangement. The relative protein levels of VEGF were significantly reduced, while the relative protein levels of HIF-1α and the MGO content significantly increased (P<0.01), and the fluorescence intensity of HIF-1α was enhanced. Compared to the model group, the WSO group and Beifuxin group showed better wound healing on day 3, 7, and 14, with an increased wound healing rate (P<0.01). The wound tissue showed clear and complete epithelial structure, reduced inflammatory cells, mature granulation tissue, and organized collagen arrangement. MGO content was significantly reduced (P<0.01). The relative protein levels of HIF-1α and VEGF both significantly increased in the WSO group, while only VEGF increased in the Beifuxin group (P<0.05 or P<0.01). Compared with the Beifuxin group, the WSO group had a thicker epidermal layer, prominent collagen formation, significantly increased HIF-1α fluorescence expression, reduced MGO content in the wound tissue, and higher relative protein levels of HIF-1α (P<0.05). ConclusionWSO can reduce the accumulation of MGO in diabetic wound tissue with yin syndrome and activate the HIF-1α/VEGF pathway, which could be one of the mechanisms for promoting wound healing.
4.Clinicopathological characteristics and prognosis analysis of 85 patients with Castleman disease
Yali WANG ; Hailong TANG ; Hongjuan DONG ; Juan FENG ; Guangxun GAO ; Li DING ; Ruifeng YUAN
Journal of Leukemia & Lymphoma 2025;34(10):592-596
Objective:To analyze the clinicopathological characteristics and prognostic factors of patients with Castleman disease (CD).Methods:A retrospective case-series study was conducted. A total of 85 patients newly diagnosed with CD in the First Affiliated Hospital of Air Force Medical University between July 2007 and August 2024 were collected. Their clinical characteristics and prognostic factors were analyzed.Results:Among the 85 patients, 45 had unicentric Castleman disease (UCD) and 40 had multicentric Castleman disease (MCD). In the UCD group, females were more commonly affected (64.4%, 29/45), with a median age of onset of 39 years. The primary lesions were mainly located in the retroperitoneum, neck, abdomen, and axilla; and the hyaline vascular subtype was the predominant pathological type (69.4%, 25/36). In the MCD group, males were more frequently affected (62.5%, 25/40), with a median age of onset of 50 years; and the plasmacytic subtype was the main pathological type (68.2%, 15/22). Compared with UCD patients, MCD patients presented more systemic symptoms and signs [85.0% (34/40) vs. 13.3% (6/45), χ2 = 43.66, P < 0.001], splenomegaly [42.5% (17/40) vs. 2.2% (1/45), χ2 = 20.58, P < 0.001], hepatomegaly [25.0% (10/40) vs. 0 (0/45), χ2 = 10.46, P = 0.001], edema or effusion in serous cavity [67.5% (27/40) vs. 8.9%(4/45), χ2 = 31.40, P < 0.001], hematological system involvement [32.5% (13/40) vs. 0 (0/44), χ2 = 16.92, P < 0.001], and renal involvement [22.5% (9/40) vs. 2.3%(1/44), χ2 = 6.36, P = 0.012]. Laboratory findings showed that the levels of hemoglobin and albumin in MCD patients were lower than those in UCD patients, while white blood cell count in MCD patients was higher than that in UCD patients. Additionally, MCD patients exhibited elevated levels of C-reactive protein, interleukin-6, vascular endothelial growth factor, erythrocyte sedimentation rate, and ferritin compared to UCD patients (all P < 0.05). Among UCD patients, 40 cases underwent simple surgical resection, with no deaths during follow-up and the 5-year overall survival (OS) rate of 100.0%; among MCD patients, 34 cases received chemotherapy, 4 received siltuximab, 3 died during follow-up with a 5-year OS rate of 87.5%; and there was no statistically significant difference in OS between the MCD and UCD groups ( χ2 = 3.67, P = 0.055). Among MCD patients, the OS of those with renal involvement (9 cases) was worse than that of those without renal involvement (31 cases) ( χ2 = 8.39, P = 0.004). Conclusions:CD is a highly heterogeneous disorder. Surgical resection is the primary treatment for UCD, with a favorable prognosis. Chemotherapy is the main treatment for MCD, with a relatively poor prognosis.
5.The Construction and Empirical Research of the Operation and Management Capability Evaluation Indicator System in Tertiary Public Hospital
Hao DING ; Aolun XU ; Jing FENG ; Yan LI ; Quan WAN ; GULIDANNA·ASIHAER ; Tiemin ZHAI
Chinese Health Economics 2025;44(5):53-57
Objective:To construct an evaluation index system for the operational management capability in tertiary public hospitals and validate its feasibility,providing a reference for accurately assessing the operational management capability of public hospitals.Methods:A literature review and Delphi method were employed to construct the index system.The Analytic Hierarchy Process was used to calculate weights,and a weighted comprehensive index method was applied to evaluate the operational management capability of sample hospitals.Results:A hierarchical indicator system was established,comprising 6 first-level indicators,16 second-level indicators,and 40 third-level indicators,covering the dimensions of resource allocation,service efficiency,economic operation,risk prevention and control,development capacity,and social benefits.Empirical results indicated that the composite score of the sample hospital decreased from 71.5 in 2019 to 53.8 in 2020 and rebounded to 57.9 by 2023.Conclusions:The empirical outcomes align well with the operational capacity as understood by the operational management personnel of the sample hospital,demonstrating that the indicator system is scientifically sound and rational,possessing a high evaluative capability.
6.Evaluation of serum cotinine cut-off value for distinguishing smoking status among Chinese adults
Changming DING ; Jin YIN ; Feng ZHAO ; Yawei LI ; Ying ZHU ; Yuebin LYU ; Xiaoming SHI
Chinese Journal of Preventive Medicine 2025;59(7):1063-1068
Objective:To determine the optimal cut-off value of serum cotinine for distinguishing smoking status among Chinese adults based on a large-scale national sample.Methods:A cross-sectional study was conducted among 8 987 Chinese adults aged 20-79 years from 152 administrative counties across 31 provinces during 2017-2018. Sociodemographic characteristics, lifestyle, smoking status, and health status were collected via questionnaires and physical examinations. Blood samples were analyzed for serum cotinine levels using liquid chromatography-mass spectrometry and for blood creatinine levels using the picric acid method. Receiver operating characteristic (ROC) curve analysis was performed with serum cotinine concentration as the test variable and self-reported smoking status as the state variable. The optimal cut-off value was determined based on the maximum Youden′s index, and the bootstrap method was used for repeated sampling (2 000 times) to evaluate the confidence interval of the cut-off value. The net reclassification index (NRI) was used to evaluate the discrimination ability of the cut-off value of this study, the cut-off value of the American population 1 (total population: 3.3 μg/L, men: 4.1 μg/L, women: 3.0 μg/L) and the cut-off value of the American population 2 (the recommended value of the United States Centers for Disease Control and Prevention for the total population: 10.0 μg/L) against the smoking status of the Chinese population. Statistical analyses were conducted using IBM SPSS 27 and Python 3.11, with a significance level of α=0.05.Results:The age of the research subjects was (49.2±15.2) years. Among them, males accounted for 49.8% (4 477); smokers accounted for 28.8% (2 586); the detection rate of serum cotinine was 94.6% (8 501), and the M ( Q1, Q3) concentration of serum cotinine was 0.9 (0.3, 85.4) μg/L. The ROC curve analysis results showed that the cut-off value (95% CI) of serum cotinine in the total population was 8.8 (6.7-11.7) μg/L, with the specificity (95% CI) about 93.6%(92.7%-94.3%), the sensitivity (95% CI) about 91.0%(89.7%-92.3%) and the area under the curve (AUC) (95% CI) about 0.93 (0.92-0.94). The cut-off value (95% CI) of cotinine for males was 17.1 (8.8-21.8) μg/L, with the specificity (95% CI) about 90.7%(87.9%-92.0%), the sensitivity (95% CI) about 89.4%(88.4%-92.2%) and the AUC (95% CI) about 0.92 (0.91-0.93). The cut-off value (95% CI) of cotinine for females was 7.4 (3.3-15.0) μg/L, with the specificity (95% CI) about 95.6%(92.7%-96.8%), the sensitivity (95% CI) about 87.6%(81.6%-92.8%) and the AUC (95% CI) about 0.92 (0.87-0.95). The NRI analysis results showed that compared with the cut-off value of the American population 2, the NRI of this study′s cut-off values in the total population, males and females were 0.020 ( P=0.015), 0.033 ( P=0.015) and 0.011 ( P=0.380), respectively, indicating that this study′s cutoff value could have better classification performance in the total population and males. Compared with the cut-off value of the American population 2, the NRI of the total population in this study was 0.001 ( P=0.285). Conclusion:The serum cotinine cut-off value based on the analysis of large sample data in China is more suitable for distinguishing the smoking status of Chinese adults.
7.Association of blood selenium exposure with sex hormones among men aged 18-79 years in China
Zheng LI ; Yingli QU ; Yawei LI ; Saisai JI ; Haocan SONG ; Qi SUN ; Miao ZHANG ; Wenli ZHANG ; Jiayi CAI ; Liang DING ; Ying ZHU ; Feng ZHAO ; Zhaojin CAO ; Yuebin LYU ; Lu WANG ; Xiaoming SHI
Chinese Journal of Preventive Medicine 2025;59(10):1632-1639
Objective:To investigate the association between blood selenium levels and sex hormones in Chinese men aged 18-79 years.Methods:Data were derived from the China National Human Biomonitoring survey conducted in 2017-2018, with a final sample size of 5 414 men. General demographic characteristics, behavioral habits, and dietary frequency were collected through questionnaires and physical examinations. Fasting blood samples were collected to measure blood lead, serum testosterone, and estradiol levels. Complex sampling linear regression models were used to analyze the associations between blood selenium levels and testosterone, estradiol, and the testosterone/estradiol ratio, adjusting for confounding factors including age, education level, marital status, smoking status, alcohol consumption, seafood intake, soy product intake, protein supplement intake, BMI, and diabetes status.Results:The mean age of the 5 414 participants was (46.85±27.91) years; 4 774 (91.65%) were of Han ethnicity and 4 505 (86.68%) were married. The median ( Q1, Q3) blood selenium concentration in men was 97.80 (80.64, 116.99) μg/L. After adjusting for confounding factors, the complex sampling linear regression model revealed negative associations between blood selenium levels and both testosterone levels and the testosterone/estradiol ratio, with a significant linear trend ( Ptrend<0.05). Compared with the Q1 group, the β (95% CI) values for testosterone in the Q2, Q3, and Q4 groups were -0.02 (-0.06 to 0.02), -0.03 (-0.08 to 0.01), and -0.06 (-0.09 to -0.02), respectively. Similarly, the β (95% CI) values for the testosterone/estradiol ratio in the Q2, Q3, and Q4 groups were -0.01 (-0.03 to 0.02), -0.01 (-0.04 to 0.04), and -0.03 (-0.06 to -0.01), respectively. Subgroup analysis indicated stronger associations between blood selenium levels and testosterone/estradiol levels in non-smoking and obese men (BMI≥28 kg/m2). Conclusion:Blood selenium levels are negatively associated with testosterone levels and the testosterone/estradiol ratio in Chinese adult males.
8.Establishment and verification of a nomogram prediction model for residual stone risk following flexible ureteroscopy lithotripsy in treating 2-3 cm renal calculi
Qi DING ; Xiaohua JIN ; Hailiang ZHU ; Cheng CAO ; Zhijiang FAN ; Wenjian TU ; Feng LI ; Bo FAN
Journal of Modern Urology 2025;30(11):967-974
Objective To develop and validate a nomogram prediction model for residual stone risk after flexible ureteroscopic lithotripsy(FURL)in patients with 2-3 cm renal calculi,so as to provide reference for treatment options.Methods Clinical data of 342 patients with renal calculi measuring 2-3 cm undergoing FURL in our hospital during Jun.2017 and Apr.2024 were retrospectively collected.At a 3∶1 randomization ratio,patients were allocated to the training cohort(n=257)and validation cohort(n=85).Patients in the training cohort were stratified into two subgroups based on postoperative stone-free status:residual stone group(n=63)and stone-free group(n=194).Logistic regression analysis was employed to identify factors influencing stone retention and construct the nomogram prediction model.Bootstrapped resampling was applied to validate the model internally,model performance was assessed with calibration curves,Hosmer-Lemeshow test was used to test the degree of fitting,receiver operating characteristic(ROC)curve was plotted to evaluate the predictive accuracy,and decision curve analysis was used to determine the clinical net benefit.The model's generalization capability was evaluated with 10-fold cross-validation of the training set.Results Multivariate logistic regression revealed that stone size,CT value,lower calyx stones,multiple stones,renal infundibulum length(RIL),and renal infundibulum width(RIW)were independent predictors of residual stones(P<0.05).The nomogram based on the above mentioned parameters demonstrated excellent discrimination,with Bootstrap-validated concordance indices of 0.876(training cohort)and 0.948(validation cohort).Hosmer-Lemeshow tests showed good calibration in both cohorts(P>0.05).ROC analysis yielded the area under the curve(AUC)of 0.876 and 0.948 for the training and validation cohorts,respectively.The optimal cutoff value was 0.253,with corresponding sensitivity of 84.13%,specificity of 78.35%,and total score of nomogram of 143.The decision curve analysis showed when the threshold probability of the training cohort and verification cohort was 0-0.81 and 0-0.97,respectively,the nomogram could obtain good clinical net benefit in predicting the risk of residual stones.The average accuracy of 10-fold cross-validation was 0.814,and the average AUC was 0.865.Conclusion The nomogram model effectively predicts residual stone risk following FURL for 2-3 cm renal calculi.It is suggested that patients with a total score of ≤143 may consider undergoing FURL.
9.Adjustment and preliminary application of a data-driven palliative care outcomes collaboration model
Yongyi CHEN ; Junchen GUO ; Jinfeng DING ; Boyong SHEN ; Ying WANG ; Zhiguo ZHOU ; Qinghui ZHANG ; Liqun LI ; Feng LIANG ; HOLLOWAY DAVID ; JOHNSON CLAIRE ; Yunyun DAI
Chinese Journal of Nursing 2025;60(18):2185-2191
Objective This study aimed to adapt the data-driven Palliative Care Outcomes Collaboration(PCOC)model to the local context and evaluate its feasibility and preliminary effectiveness in a palliative care unit in China,with the goal of informing its broader integration into national palliative care practice.Methods Based on international experience,a localized implementation protocol for the PCOC model was developed through expert con-sultations and a pilot study.The protocol incorporated key elements including organizational and managerial sup-port,team training and capacity building,information system integration,supervision and feedback mechanisms,pro-cess optimization,and data-driven decision-making.From June to December 2023,the protocol was piloted in the palliative care unit of a tertiary cancer hospital in Changsha,China.Implementation outcomes were assessed by comparing patients' urgent care response rates,symptom stability rates,and symptom improvement rates between the first 1~3 months and 4~6 months after implementation.Results During the study period,a total of 355 inpatients were enrolled,with the PCOC assessment achieving full coverage(100%)and a completion rate of 97.78%.There was no statistically significant difference in the urgent needs response rate between the first 1~3 months and the 4~6 months after the implementation of the PCOC model(P=0.533).However,compared to the first 1~3 months af-ter implementation,patients in the 4~6 months period showed significantly higher symptom stability rates for pain,psychological/spiritual issues,and family/caregiver problems,as well as a higher improvement rate for pain(P<0.05).Conclusion The localized PCOC implementation protocol facilitates standardized assessment and symptom manage-ment,and its application can enhance the quality of palliative care.
10.Design, synthesis and pharmacological evaluation of 1,2,3,4-tetrahydrobenzofuro2,3-cpyridine derivatives as p21-activated kinase 4 inhibitors for treatment of pancreatic cancer.
Yang LI ; Yan FANG ; Xiaoyu CHEN ; Linjiang TONG ; Fang FENG ; Qianqian ZHOU ; Shulun CHEN ; Jian DING ; Hua XIE ; Ao ZHANG
Acta Pharmaceutica Sinica B 2025;15(1):438-466
The p21-activated kinase 4 (PAK4), a key regulator of malignancy, is negatively correlated with immune infiltration and has become an emergent drug target of cancer therapy. Given the lack of high efficacy PAK4 inhibitors, we herein reported the identification of a novel inhibitor 13 bearing a tetrahydrobenzofuro[2,3-c]pyridine tricyclic core and possessing high potency against MIA PaCa-2 and Pan02 cell lines with IC50 values of 0.38 and 0.50 μmol/L, respectively. This compound directly binds to PAK4 in a non-ATP competitive manner. In the mouse Pan02 model, compound 13 exhibited significant tumor growth inhibition at a dose of 100 mg/kg, accompanied by reduced levels of PAK4 and its phosphorylation together with immune infiltration in mice tumor tissue. Overall, compound 13 is a novel allosteric PAK4 inhibitor with a unique tricyclic structural feature and high potency both in vitro and in vivo, thus making it worthy of further exploration.

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