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.
9.Genetic analysis of a patient with Rod-shaped myopathy due to variants of NEB gene
Weirong ZHENG ; Xiaoyan PENG ; Yuqing LEI ; Liwen WANG ; Xinrui WANG ; Qianqian ZHAO
Chinese Journal of Medical Genetics 2024;41(12):1473-1477
Objective:To explore the genetic etiology of a child with Nemaline myopathy (NM).Methods:A child who had visited Fujian Children′s Hospital on January 28, 2023 due to " phlegm in the throat for more than a month" was selected as the study subject. Clinical data of the child was collected, in addition with peripheral blood samples from her and her parents. Following extraction of genomic DNA, trio-whole exome sequencing (WES) was carried out. Candidate variants was verified by Sanger sequencing and bioinformatic analysis. This study has been approved by the Medical Ethics Committee of Fujian Children′s Hospital (Ethic No. 2023ETKLRK2004).Results:The patient, a 2-month-old female, had presented with persistent phlegm in the throat, recurrent severe pneumonia, swallowing difficulty, and decreased muscle tone. WES results revealed that she has harbored compound heterozygous variants of the NEB (NM_001271208.1) gene, namely c. 4611+ 2T>A and c. 12961del (p.Ser4321ALafs*21), and the associated disease is rod-like myopathy. Sanger sequencing confirms that the variants were respectively inherited from her mother and father, both of whom had normal phenotypes. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as likely pathogenic (PVS1_Moderate+ PM2_Supporting+ PM3; PVS1+ PM2_Supporting). Conclusion:The c.4611+ 2T>A/c.12961del (p.Ser4321ALafs*21) compound heterozygous variants of the NEB gene probably underlay the pathogenesis in this child. Above findings has facilitated the diagnosis, genetic counseling, and guidance for reproductive decision of her family.
10.Genetic analysis of a patient with Rod-shaped myopathy due to variants of NEB gene.
Weirong ZHENG ; Xiaoyan PENG ; Yuqing LEI ; Liwen WANG ; Xinrui WANG ; Qianqian ZHAO
Chinese Journal of Medical Genetics 2024;41(12):1473-1477
OBJECTIVE:
To explore the genetic etiology of a child with Nemaline myopathy (NM).
METHODS:
A child who had visited Fujian Children's Hospital on January 28, 2023 due to "phlegm in the throat for more than a month" was selected as the study subject. Clinical data of the child was collected, in addition with peripheral blood samples from her and her parents. Following extraction of genomic DNA, trio-whole exome sequencing (WES) was carried out. Candidate variants was verified by Sanger sequencing and bioinformatic analysis. This study has been approved by the Medical Ethics Committee of Fujian Children's Hospital (Ethic No. 2023ETKLRK2004).
RESULTS:
The patient, a 2-month-old female, had presented with persistent phlegm in the throat, recurrent severe pneumonia, swallowing difficulty, and decreased muscle tone. WES results revealed that she has harbored compound heterozygous variants of the NEB (NM_001271208.1) gene, namely c.4611+2T>A and c.12961del (p.Ser4321ALafs*21), and the associated disease is rod-like myopathy. Sanger sequencing confirms that the variants were respectively inherited from her mother and father, both of whom had normal phenotypes. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as likely pathogenic (PVS1_Moderate+PM2_Supporting+PM3; PVS1+PM2_Supporting).
CONCLUSION
The c.4611+2T>A/c.12961del (p.Ser4321ALafs*21) compound heterozygous variants of the NEB gene probably underlay the pathogenesis in this child. Above findings has facilitated the diagnosis, genetic counseling, and guidance for reproductive decision of her family.
Humans
;
Female
;
Myopathies, Nemaline/genetics*
;
Infant
;
Muscle Proteins/genetics*
;
Mutation
;
Exome Sequencing
;
Genetic Testing


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