1.B7-H3 molecule inhibits apoptosis of non-small cell lung cancer cells via the SIRT1/p53 signaling pathway
Lin ZHENG ; Jianxin ZHONG ; Ke NIU ; Qing XU ; Huijuan LING ; Yayu ZHU ; Bing CHEN ; Liwen CHEN
Acta Universitatis Medicinalis Anhui 2026;61(2):232-238
ObjectiveTo explore the role of the histone deacetylase Sirtuin-1 (SIRT1)/p53 signaling pathway in promoting apoptosis of non-small cell lung cancer cells (NSCLC) induced by the co-stimulatory molecule B7 homolog 3 (B7-H3). MethodsThe GEPIA 2 platform was used for survival analysis of NSCLC patients based on B7⁃H3 gene expression levels. The Gene Enrichment Analysis (GSEA) method was used to analyze the enrichment characteristics of B7⁃H3 molecules in the gene set of cell apoptosis. In the non-small cell lung cancer A549 cell line, B7⁃H3 was knocked down, and the protein expression levels of SIRT1 and p53 were detected by Western blot. B7⁃H3 was overexpressed in A549 cells and the apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining. Overexpression of B7⁃H3 and knockdown of SIRT1 were performed in A549 cell line. The expression levels of p53 and apoptosis-related proteins B-cell lymphoma/leukemia-2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected respectively by Western blot. Cell apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining. ResultsThe overall survival of the B7-H3 high-expression group was significantly lower than that of the low-expression group (P<0.01). B7-H3 was significantly enriched in the cell apoptosis signaling pathway and the p53 signaling pathway (P<0.05). Compared with the control group, the expression of SIRT1 was significantly downregulated, and p53 was significantly upregulated in the B7⁃H3 knockdown group (both P<0.001). Overexpression of B7-H3 significantly up-regulated SIRT1 protein expression (P<0.05), down-regulated p53 expression (P<0.01), and markedly increased the Bcl-2/Bax ratio of apoptosis-related proteins (P<0.001). The results of Annexin V/PI double staining showed that the apoptosis rate of A549 cells with overexpressed B7⁃H3 decreased (the apoptosis rate of the control group was 26.72%±4.13%, while that of the B7⁃H3 overexpression group was 13.87%±0.82%; P<0.01). In B7-H3-overexpressing cell lines, SIRT1 knockdown significantly reversed apoptosis (P<0.05), up-regulated p53 protein expression (P<0.001), and markedly reduced the Bcl-2/Bax ratio (P<0.001). ConclusionB7-H3 molecule inhibits the apoptosis of non-small cell lung cancer cells via the SIRT1/p53 signaling pathway.
2.Clinical significance and diagnostic value of exosome B7-H3 in plasma from NSCLC
Qing Xu ; Lin Zheng ; Huijuan Ling ; Yayu Zhu ; Ke Niu ; Liwen Chen
Acta Universitatis Medicinalis Anhui 2025;60(6):1120-1126
Objective :
To establish an enzyme-linked immunosorbent assay (ELISA) for exosome B7-H3 in plas- ma , and to explore the clinical significance and diagnostic value of exosome B7-H3 in plasma from non-small cell lung cancer (NSCLC) .
Methods :
The plasma of 70 NSCLC patients (NSCLC group) and 36 healthy controls (HC group) were collected . Exosomes and microvesicles in plasma were separated by ultra-fast centrifuge method , and the expression levels of B7-H3 in plasma exosomes in NSCLC groups and HC groups were compared by Western blot method . In NSCLC group , the expression levels of B7-H3 in plasma exosomes and microvesicles in NSCLC group were compared . A simple and feasible ELISA method was established to detect the expression level of exosome B7 - H3 in plasma by means of polyethylene glycol (PEG) precipitation and its clinical significance was analyzed . Lo- gistic regression model was established to predict plasma-derived exosome B7-H3 as a risk factor , and receiver op- erating characteristic curve (ROC) was used to investigate the diagnostic value of exosome B7-H3 in NSCLC .
Results:
For exosomes and microvesicles in plasma which were extracted by ultracentrifugation , Western blot results showed that the expression level of B7-H3 in plasma exosomes of NSCLC group was higher than that of HC group (P = 0. 032) , and the expression level of B7-H3 in plasma exosomes was higher than that of microvesicles of NSCLC group (P = 0. 012) . The expression level of exosome B7-H3 in plasma extracted by PEG precipitation was also higher in NSCLC group than that in HC group (P = 0. 024) . The expression level of exosome B7-H3 in plasma of NSCLC patients was not related to gender , age , smoking or pathological type , but was related to T stage (P = 0. 002) , N stage (P < 0. 001) , M stage (P = 0. 010) and AJCC stage (P < 0. 001) . Multivariate Logistic regres- sion analysis identified exosome B7-H3 in plasma as a risk factor for NSCLC . ROC analysis showed that the sensi- tivity of exosome B7-H3 in plasma for the diagnosis of NSCLC (0. 843) was higher than that of carcinoembryonic antigen (CEA) (0. 743) , whereas the specificity (0. 722) was lower than that of CEA (0. 833) . Combined de- tection of exosome B7-H3 and CEA (AUC = 0. 928 , 95% CI:0. 877 - 0. 979) had a higher diagnostic performance for NSCLC .
Conclusion
B7-H3 in plasma exosomes is related to the cancer staging of NSCLC , and the combined detection of exosome B7-H3 and CEA in plasma is conducive to the laboratory diagnosis of NSCLC .
3.A cisplatin prodrug-based self-assembling ozone delivery nanosystem sensitizes radiotherapy in triple-negative breast cancer.
Tianyue XU ; Dan ZHENG ; Meixu CHEN ; Linlin SONG ; Zhihui LIU ; Yan CHENG ; Yujie ZHAO ; Liwen HUANG ; Yixuan LI ; Zhankun YANG ; Cong LI ; Biao DONG ; Jing JING ; Hubing SHI
Acta Pharmaceutica Sinica B 2025;15(5):2703-2722
Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.
4.Teaching reform of obstetrics and gynecology course in preventive medicine based on integration of medical care and prevention
Guanghua WANG ; Danfeng GAO ; Liwen SONG ; Zheng BIAN ; Yaoling WANG ; Danni CHEN ; Jin QIU
Chinese Journal of Medical Education Research 2025;24(11):1518-1522
Under the Healthy China strategy, the training of preventive medicine professionals should conform to the development of the times and the needs of public health. The article analyzed the problem of "disconnection between medical care and prevention" in teaching the course of Obstetrics and Gynecology for students majoring in preventive medicine, and proposed to strengthen the strategy of "integration of medical care and prevention". Guided by the concepts of "Comprehensive Health", with the cornerstone of cultivating morality and talents, the reform focused on enhancing the post competency of preventive medicine talents. Course content was optimized by reinforcing prevention-focused elements, student-centered teaching method innovation was advocated, and simulation-based training teaching system was established. Moreover, projects integrating science and education were used to improve faculty teaching capacity with tiered and diversified approaches. Course assessment methods were revised and "ideological and political education" was incorporated to establish the education concept of "emphasis on prevention and integration of medical care and prevention". The survey showed that these reform measures effectively improved the comprehensive clinical literacy of preventive medicine students in obstetrics and gynecology, which is of great significance for building a "integration of medical care and prevention" public health talent training model. In the future, the long-term effectiveness of course reform will be ensured from the perspectives of teaching resources, personnel investment, and policy support.
5.Analysis of Differences in Cortical Activation Areas and Functional Connectivity During Speech in Young People Under Different Cognitive Loads
Zihui JIANG ; Xiuen CHEN ; Jiejiao ZHENG ; Yongjun ZHENG ; Yunyun ZHANG ; Xiangyun LIU ; Liwen QIU ; Chenchen ZHANG ; Zhichao NING
Journal of Audiology and Speech Pathology 2025;33(1):40-45
Objective To investigate the differences in cortical activation and functional connectivity during speech under different cognitive loads in young individuals.Methods Twenty-one participants(mean age 21.9±1.33 years)were instructed to read short sentences embedded with color words under both congruent(where the color words matched the font color)and incongruent(where the color words did not match the font color)condi-tions.The color words required reading the font color instead of the word itself.Functional near-infrared spectros-copy(fNIRS)was utilized to analyze differences in cortical activation(changes in HbO concentration)and functional connectivity(Pearson correlation of HbO between brain regions)in the dorsolateral prefrontal cortex(DLPFC)and supplementary motor area(SMA)bilaterally.Results The fNIRS results revealed significant increase in HbO con-centration changes in the RDLPFC(t=3.4,P=0.003),LDLPFC(t=2.58,P=0.019),RSMA(t=3.59,P=0.002),and LSMA(t=4.06,P=0.001)under the incongruent condition compared to the congruent condition.Additionally,there was a significant enhancement in the correlation between RDLPFC and LDLPFC(t=2.44,P=0.025).However,the differences in correlation between left and right SMA,as well as between SMA and DLPFC,were not statistically significant(P>0.05).Conclusion These findings suggest that during speech under incongru-ent conditions,increased cognitive load leads to elevated cortical activation in the DLPFC and SMA,along with in-creased functional connectivity between the left and right DLPFC.
6.Teaching reform of obstetrics and gynecology course in preventive medicine based on integration of medical care and prevention
Guanghua WANG ; Danfeng GAO ; Liwen SONG ; Zheng BIAN ; Yaoling WANG ; Danni CHEN ; Jin QIU
Chinese Journal of Medical Education Research 2025;24(11):1518-1522
Under the Healthy China strategy, the training of preventive medicine professionals should conform to the development of the times and the needs of public health. The article analyzed the problem of "disconnection between medical care and prevention" in teaching the course of Obstetrics and Gynecology for students majoring in preventive medicine, and proposed to strengthen the strategy of "integration of medical care and prevention". Guided by the concepts of "Comprehensive Health", with the cornerstone of cultivating morality and talents, the reform focused on enhancing the post competency of preventive medicine talents. Course content was optimized by reinforcing prevention-focused elements, student-centered teaching method innovation was advocated, and simulation-based training teaching system was established. Moreover, projects integrating science and education were used to improve faculty teaching capacity with tiered and diversified approaches. Course assessment methods were revised and "ideological and political education" was incorporated to establish the education concept of "emphasis on prevention and integration of medical care and prevention". The survey showed that these reform measures effectively improved the comprehensive clinical literacy of preventive medicine students in obstetrics and gynecology, which is of great significance for building a "integration of medical care and prevention" public health talent training model. In the future, the long-term effectiveness of course reform will be ensured from the perspectives of teaching resources, personnel investment, and policy support.
7.Analysis of Differences in Cortical Activation Areas and Functional Connectivity During Speech in Young People Under Different Cognitive Loads
Zihui JIANG ; Xiuen CHEN ; Jiejiao ZHENG ; Yongjun ZHENG ; Yunyun ZHANG ; Xiangyun LIU ; Liwen QIU ; Chenchen ZHANG ; Zhichao NING
Journal of Audiology and Speech Pathology 2025;33(1):40-45
Objective To investigate the differences in cortical activation and functional connectivity during speech under different cognitive loads in young individuals.Methods Twenty-one participants(mean age 21.9±1.33 years)were instructed to read short sentences embedded with color words under both congruent(where the color words matched the font color)and incongruent(where the color words did not match the font color)condi-tions.The color words required reading the font color instead of the word itself.Functional near-infrared spectros-copy(fNIRS)was utilized to analyze differences in cortical activation(changes in HbO concentration)and functional connectivity(Pearson correlation of HbO between brain regions)in the dorsolateral prefrontal cortex(DLPFC)and supplementary motor area(SMA)bilaterally.Results The fNIRS results revealed significant increase in HbO con-centration changes in the RDLPFC(t=3.4,P=0.003),LDLPFC(t=2.58,P=0.019),RSMA(t=3.59,P=0.002),and LSMA(t=4.06,P=0.001)under the incongruent condition compared to the congruent condition.Additionally,there was a significant enhancement in the correlation between RDLPFC and LDLPFC(t=2.44,P=0.025).However,the differences in correlation between left and right SMA,as well as between SMA and DLPFC,were not statistically significant(P>0.05).Conclusion These findings suggest that during speech under incongru-ent conditions,increased cognitive load leads to elevated cortical activation in the DLPFC and SMA,along with in-creased functional connectivity between the left and right DLPFC.
8.Differential expression and clinical significance of miR-124-3p in β-thalassemia
Luoyuan CAO ; Wenxu DONG ; Jing YANG ; Liwen GUO ; Jiaojiao LU ; Xian ZHENG ; Xianguo FU
Basic & Clinical Medicine 2024;44(12):1633-1637
Objective To investigate the differential expression of miR-124-3p in peripheral blood and clinical sig-nificance of patients with β-thalassemia.Methods Peripheral blood samples were collected from 33 patients with β-thalassemia and 30 healthy controls in Ningde Municipal Hospital Affiliated to Ningde Normal University from June 2021 to August 2022.The expression level of miR-124-3p was detected.Luciferase reporter gene was used to verify the interaction between miR-124-3p and ERF 3'UTR.The correlation between differential expression of miR-124-3p and β-thalassemia was analyzed and the clinical diagnostic value of miR-124-3p for β-thalassemia was eval-uated.Results Compared with healthy control individuals,the expression of miR-124-3p was significantly up-reg-ulated in patients with β-thalassemia(P<0.001).The genotype of miR-124-3p high expression group was 84.2%β0(16/19),the genotype of low expression group was 55.6%β+(10/18).ROC curve analysis showed that miR-124-3p had predictive efficacy for β-thalassemia(AUC:0.842).Luciferase reporter gene analysis showed that ERF gene was the regulatory target of miR-124-3p.Conclusions The differential expression of miR-124-3p in patients with β-thalassemia is closely related to the genotype and clinical severity of thalassemia,and ERF is negatively reg-ulated by miR-124-3p.miR-124-3p may be an effective diagnostic biomarker for β-thalassemia.
9.Efficacy and safety of transcatheter arterial infusion chemotherapy with gemcitabine and nab-paclitaxel regimen for advanced pancreatic cancer
Zhewei ZHANG ; Hui ZENG ; Jiaping ZHENG ; Jun LUO ; Liwen GUO ; Fei CAO ; Weiren LIANG ; Guoliang SHAO
Journal of Interventional Radiology 2024;33(5):512-515
Objective To evaluate the clinical efficacy and safety of transcatheter arterial infusion with gemcitabine and nab-paclitaxel(GN)as first-line therapy in treating patients with advanced pancreatic cancer.Methods The clinical data of a total of 50 patients with advanced pancreatic cancer,who were treated with transcatheter arterial infusion chemotherapy with GN regimen at the Zhejiang Cancer Hospital of China between January 2016 and December2020,were collected The objective effective rate(ORR),progression-free survival(PFS),overall survival(OS)and treatment-related toxic reactions were analyzed.Results A total of 236 times of transcatheter arterial infusion chemotherapy were carried out in the 50 patients,with an average perfusion procedure of 4.72 times per patient.Complete remission(CR)was obtained in 0 patient,partial remission(PR)in 16 patients,and stable disease(SD)in 21 patients.The ORR was 32%,the median PFSwas5.1 months,and the OS was 9.8 months.The main adverse events included neutropenia,thrombocytopenia,vomiting,nausea,fatigue,etc.Conclusion For patients with advanced pancreatic cancer,transcatheter arterial infusion chemotherapy with GN regimen carries good short-term efficacy and safety,it can improve patient's PFS and OS to a certain extent.(J Intervent Radiol,2024,33:512-515)
10.An advanced machine learning method for simultaneous breast cancer risk prediction and risk ranking in Chinese population: A prospective cohort and modeling study
Liyuan LIU ; Yong HE ; Chunyu KAO ; Yeye FAN ; Fu YANG ; Fei WANG ; Lixiang YU ; Fei ZHOU ; Yujuan XIANG ; Shuya HUANG ; Chao ZHENG ; Han CAI ; Heling BAO ; Liwen FANG ; Linhong WANG ; Zengjing CHEN ; Zhigang YU
Chinese Medical Journal 2024;137(17):2084-2091
Background::Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors.Methods::The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020.Results::The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy.Conclusions::We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.


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