1.Role and mechanism of mitochondrial calcium uniporter in the cytoskeleton of pancreatic ductal epithelial cells in a mouse model of acute pancreatitis
Qiaofeng CHEN ; Qingzi FU ; Huiying YANG ; Junbo HONG ; Liang ZHU ; Zhenzhen YANG ; Guodu TANG ; Shiyu ZHANG
Journal of Clinical Hepatology 2026;42(2):400-408
ObjectiveTo investigate the effect of mitochondrial calcium uniporter (MCU) on the cytoskeleton of pancreatic ductal epithelial cells in a mouse model of acute pancreatitis (AP) induced by caerulein (CAE), to analyze the role of MCU in the development of AP, and to provide a theoretical basis for clinical treatment. MethodsIn the in vivo experiment, wild-type male C57BL6/J mice, aged 4 weeks, were randomly divided into control group and AP group, with 6 mice in each group. The mice in the AP group were given intraperitoneal injection of CAE to establish a model of AP, and those in the control group were given intraperitoneal injection of an equal volume of normal saline. Serum and pancreatic tissue samples were collected after 24 hours of modeling. HE staining was used to observe pancreatic histopathological changes; Western Blot was used to measure the expression levels of MCU, glutathione peroxidase 4 (GPX4), and acyl-CoA synthetase long chain family member 4 (ASCL4); kits were used to measure the serum level of amylase. In the in vitro experiment, the human pancreatic ductal epithelial cell line HPDE6-C7 was co-cultured with CAE for 24 hours to establish an in vitro AP model, and the cells were divided into control group, CAE group, RR (an MCU activity inhibitor) group, CAE+RR group, Fer-1 (an ferroptosis inhibitor) group, CAE+Fer-1 group, Erastin (an ferroptosis inducer) group, and CAE+Erastin group. CCK-8 assay was used to observe the influence of different agents on cell viability; Western Blot was used to measure the expression levels of MCU, GPX4, and ASCL4; immunofluorescence assay was used to measure reactive oxygen species (ROS), actin cytoskeleton, and monolayer permeability; kits were used to measure the concentrations of malondialdehyde (MDA), glutathione (GSH), Fe2+, and total iron. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for comparison between two groups. ResultsIn the in vivo experiment, compared with the control group, the AP group had significant increases in pancreatic histopathological score, the serum level of amylase, and the expression levels of MCU and ASCL4, as well as a significant reduction in the expression of GPX4 (all P<0.05). In the in vitro experiment, compared with the control group, the CAE group had significant increases in the expression levels of MCU and ASCL4, a significant reduction in the expression of GPX4, and significant increases in the concentrations of Fe2+, total iron, and MDA, the green fluorescence intensity of ROS, and monolayer permeability, as well as a significant reduction in the concentration of GSH (all P<0.05), with the presence of actin cytoskeleton disruption. Compared with the CAE group, the CAE+RR group had a significant increase in the expression level of GPX4, a significant reduction in the expression level of ASCL4, and significant reductions in the concentrations of Fe2+, total iron, and MDA, the green fluorescence intensity of ROS, and monolayer permeability and a significant increase in the concentration of GSH (all P<0.05), with alleviation of actin cytoskeleton disruption. Compared with the CAE group, the CAE+Fer-1 group had significant reductions in the concentrations of Fe2+, total iron, and MDA, the green fluorescence intensity of ROS, and monolayer permeability and a significant increase in the concentration of GSH (all P<0.05), with alleviation of actin cytoskeleton disruption. Compared with the CAE group, the CAE+Erastin group had significant increases in the concentrations of Fe2+, total iron, and MDA, the green fluorescence intensity of ROS, and monolayer permeability and a significant reduction in the concentration of GSH (all P<0.05), with aggravation of actin cytoskeleton disruption. ConclusionDuring the onset of AP, MCU mediates oxidative stress-induced ferroptosis and leads to the disruption of the pancreatic ductal epithelial barrier, which may be one of the possible pathogeneses of AP.
2.Study on pharmacy dispensing fee system in the United States and its implications for China
Shiyu LIAO ; Lin WU ; Yongfa CHEN
China Pharmacy 2026;37(7):842-847
OBJECTIVE To draw upon the United States’ experience in charging for drug dispensing services and provide reference for designing China’s fee scheme for such services. METHODS Relevant literature and official websites were reviewed to systematically summarize the evolution of dispensing fees in the U.S., charging methods and standards across different health insurance plans, and factors influencing fee determination. The key characteristics of the U.S. fee system were summarized. Recommendations for improving China’s related practices were then proposed. RESULTS & CONCLUSIONS The U.S. dispensing fee system has undergone four stages of conceptual emergence, model exploration, system establishment, and professional development, forming a prescription-based charging model independent of drug prices. Under a unified federal framework, health insurance programs set a differentiated dispensing fee system based on actual costs and factors such as drug category, pharmacy type, prescription volume, and policy objectives, reflecting pharmacists’ professional value and ensuring sustainable service provision. Although China has recognized dispensing fees at the national level, implementation still faces barriers including insufficient value recognition and pressure on medical insurance payment. Drawing on U.S. experience and considering China’s national context, it is recommended to strengthen empirical research on the value assessment of dispensing services to support medical insurance decision-making; standardize the methodology for dispensing cost measurement and clarify the basis for fee setting by incorporating pharmacists’ professional and technical value as well as public interests; explore differentiated charging models at the provincial level with prescriptions as the basic unit, with emphasis on professional expertise and dispensing risks, and continuously strengthen pharmacists’ professional capacity to facilitate the scientific formulation and effective implementation of dispensing service fee policies.
3.Advances in Diabetic Peripheral Neuropathy Treatment by Traditional Chinese Medicine Based on Cellular Senescence: A Review
Qixian MA ; Shiyu HAN ; Hui HUANG ; Jing TIAN ; Xu HAN ; Qingguang CHEN ; Hao LU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):322-330
Diabetic Peripheral Neuropathy (DPN) is one of the most common and harmful complications of type 2 diabetes. DPN's pathogenesis include high blood sugar-induced oxidative stress, inflammation, and mitochondrial dysfunction. These factors are combined to damage nerve fibers, leading to sensory issues, pain, and numbness. Through a coordinated effect, these factors trigger nerve fiber damage and lead to sensory abnormalities, pain and numbness in limbs, and other symptoms, seriously restricting patients' activities of daily living and mobility. Recent research highlights that cellular senescence plays a critical role in DPN. Cellular senescence is manifested by the loss of cell proliferation ability, and further aggravates nerve damage via oxidative stress, mitochondrial dysfunction, autophagy impairment, inflammatory reaction, and other mechanisms, accelerating DPN occurrence and progression. In terms of medical treatment, current methods focus on blood sugar control, pain relief medicine, and microcirculation improvement, while no therapy has been developed based on cellular senescence. In contrast, traditional Chinese medicine (TCM) shows a unique advantage in DPN prevention and treatment via cellular senescence modulation. TCM emphasizes a holistic approach, as well as syndrome differentiation and treatment, effective in anti-aging and nerve damage repair. Recent studies show that TCM active ingredients, including puerarin, ginsenosides, and berberine, can reduce inflammation, oxidative stress, and apoptosis via signaling pathway regulation, thereby slowing cellular senescence to alleviate nerve damage. Furthermore, TCM compounds such as Buyang Huanwutang, Taohong Siwutang, and Huangqi Guizhi Wuwutang exert synergistic effects on cellular senescence-related pathways to improve nerve health and reduce DPN clinical symptoms. Therefore, this paper reviews the literature related to the interaction between cellular senescence and DPN from the perspective of cellular senescence, summarizing the mechanism of DPN and TCM intervention strategies.
4.The mechanism of Prim-O-glucosylcimifugin in improving cholesterol metabolism in osteoarthritis chondrocytes via lncRNA NEAT1/miR-128-3p
Yanming LIN ; Haishui TU ; Shujie LAN ; Chao LI ; Shiyu LU ; Yue CHEN ; Changlong FU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):55-67
Objective:
To investigate the mechanism of action of Prim-O-glucosylcimifugin (POG) to improve cholesterol metabolism in osteoarthritic (OA) chondrocytes based on the long noncoding RNA nuclear-enriched transcript 1 (lncRNA NEAT1)/microRNA-128-3p (miR-128-3p) pathway.
Methods:
For in vivo experiments, 60 mice were divided into the normal, sham operation, model, and POG groups using the random number table method, with 15 mice per group. The osteoarthritis mouse model was constructed using the modified Hulth method in the model and POG groups. Mice in the POG group were administered 30 mg/(kg·d)POG by gavage. The other groups were administered an equal amount of normal saline for 8 weeks. The cartilage tissue structure of mice in each group was observed using hematoxylin and eosin staining. Real-time PCR was used to detect changes in the lncRNA NEAT1 and miR-128-3p mRNA expression levels in the cartilage tissues of mice. Western blotting was used to detect the protein expressions of ATP-binding cassette transporter A1 (ABCA1), liver X receptor β (LXRβ), matrix metalloprotein-3 (MMP-3), and B-lymphoblastoma-2-associated X protein (Bax) in articular cartilage of mice. An enzyme-linked immunosorbent assay was used to measure the tumor necrosis factor-α (TNF-α) content in the synovial fluid of mice. A biochemical microplate assay was used to measure the total cholesterol level in the synovial fluid of mice. The in vitro experiments were divided into the negative control, interleukin-1β(IL-1β), IL-1β+ POG, IL-1β+ oe-lncRNA NEAT1, IL-1β+ oe-lncRNA NEAT1 + POG, IL-1β + miR-128-3p inhibition, and IL-1β+ miR-128-3p inhibition+ POG groups. An OA model was established by inducing chondrocytes with IL-1β for 24 h, and 90 mg/L of POG and miR-128-3p inhibitor(50 nmol/L) were administered for 48 h as an intervention. lncRNA NEAT1 expression in chondrocytes was detected using fluorescence in situ hybridization. A dual luciferase assay was used to detect the targeting relationship between lncRNA NEAT1 and miR-128-3p. Lentiviral plasmids overexpressing lncRNA NEAT1 were used to transfect mouse chondrocytes. Real-time PCR was used to detect the effect of lncRNA NEAT1 overexpression on the mRNA level of miR-128-3p in chondrocytes. Western blotting was used to detect ABCA1, LXRβ, MMP-3, and Bax protein expression in chondrocytes after lncRNA NEAT1 overexpression and miR-128-3p inhibition.
Results:
POG significantly reduced OA cartilage tissue damage. Compared with the model group, the lncRNA NEAT1 mRNA level decreased, whereas the miR-128-3p mRNA level increased in the cartilage tissue of the POG group (P<0.05). Compared with the model group, ABCA1 and LXRβ protein expression increased in the POG group, whereas MMP-3 and Bax protein expression decreased (P<0.05). The TNF-α levels decreased in the POG group compared to the model group (P<0.05). Compared with the model group, the total cholesterol level in the synovial fluid of the joint of mice in the POG group decreased (P<0.05). The mean fluorescence intensity of lncRNA NEAT1 in the IL-1β+ POG group decreased compared with the IL-1β group (P<0.05). The relative luciferase activity in the miR-128-3p mimics group bound to the lncRNA NEAT1-WT plasmid decreased compared with the miR-128-3p negative control group (P<0.05). The lncRNA NEAT1 mRNA levels decreased, whereas the miR-128-3p mRNA levels increased in the IL-1β+ oe-lncRNA NEAT1 + POG group compared with the IL-1β+ oe-lncRNA NEAT1 group (P<0.05). Compared with the IL-1β+ POG group, ABCA1 and LXRβ protein expression decreased, whereas MMP-3 and Bax protein expression increased (P<0.05).
Conclusion
POG mediates lncRNA NEAT1/miR-128-3p to improve cholesterol metabolism in OA chondrocytes.
5.Setup Error and Its Influencing Factors in Radiotherapy for Spinal Metastasis
Wenhua QIN ; Xin FENG ; Zengzhou WANG ; Shangnan CHU ; Hong WANG ; Shiyu WU ; Cheng CHEN ; Fukui HUAN ; Bin LIANG ; Tao ZHANG
Cancer Research on Prevention and Treatment 2025;52(5):400-404
Objective To investigate the setup error in patients with spinal bone metastasis who underwent radiotherapy under the guidance of kilovoltage cone-beam CT (KV-CBCT). Methods A total of 118 patients with spinal metastasis who underwent radiotherapy, including 17 cases of cervical spine, 62 cases of thoracic spine, and 39 cases of lumbar spine, were collected. KV-CBCT scans were performed using the linear accelerators from Elekta and Varian’s EDGE system. CBCT images were registered with reference CT images in the bone window mode. A total of 973 data were collected, and 3D linear errors were recorded. Results The patients with spinal bone metastasis were grouped by site, height, weight, and BMI. The P value of the patients grouped only by site was P<0.05, which was statistically significant. Conclusion When grouped by site in the 3D direction, the positioning effect of cervical spine is better than that of thoracic and lumbar spine. The positioning effect of the thoracic spine is better in the head and foot direction but worse in the left and right direction compared with that of the lumbar spine. Instead of extending or narrowing the margin according to the BMI of patients with spinal metastasis, the margin must be changed according to the site of spinal bone metastasis.
6.Application of blood conservation measures with different red blood cell transfusion volumes in obstetrics and their impact on postpartum outcomes
Huimin DENG ; Fengcheng XU ; Meiting LI ; Lan HU ; Xiao WANG ; Shiyu WANG ; Xiaofei YUAN ; Jun ZHENG ; Zehua DONG ; Yuanshan LU ; Shaoheng CHEN
Chinese Journal of Blood Transfusion 2025;38(5):691-698
Objective: To evaluate the application of blood conservation measures in obstetric patients with different red blood cell transfusion volumes and to assess the impact of different transfusion volumes on postpartum outcomes. Methods: A retrospective investigation was conducted on 448 obstetric patients who received blood transfusions at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. Patients were divided into four groups (1-2 units group, 3-4 units group, 5-6 units group, and >6 units group) based on the volumes of red blood cells (RBCs) transfused during and within 7 days after delivery. The maternal physiological indicators, pre- and postpartum laboratory test indicators, obstetric complications, application of blood conservation measures, use of blood products, and postpartum outcomes were reviewed. The clinical characteristics, application of blood conservation measures, and their impact on postpartum outcomes were compared among different transfusion groups. Results: There were statistically significant differences in the multivariate logistic analysis of history of previous cesarean section (OR=1.781), eclampsia/pre-eclampsia/(OR=1.972) and postpartum blood loss>1 000 mL(OR=1.699)(P<0.05) among different transfusion groups. In terms of blood conservation measures, the more RBCs transfused, the higher the rate of mothers receiving blood conservation measures such as balloon occlusion, arterial ligation, autologous blood transfusion with a cell saver, and hysterectomy. With the increase in the volume of RBCs transfusion, the demand for fresh frozen plasma(FFP), cryoprecipitate, and platelet transfusions also increased. The hospitalization days for the four groups of parturients were 6.0 (4.0-9.0), 7.5 (5.0-14.8), 7.0 (4.5-13.0) and 11.0 (9.0-20.5), respectively (P<0.05) and the rates of ICU transfer were 2.0% (5/250), 9.4% (12/128),18.2% (6/33) and 51.4% (19/37), respectively (P<0.05). Both increased significantly with the increase in the volume of RBCs transfusion, and the differences between groups were statistically significant. Conclusion: Parturients who received higher volume of RBCs had multiple risks factors for bleeding before childbirth, had higher postpartum blood loss, and had a higher rate of application of various blood conservation measures. In addition, an increase in the volume of RBCs transfusion may have adverse effects on postpartum recovery.
7.Chondrocyte proliferation and tissue formation enhanced by stromal cell derived factor-1 modified poly-L-lactic acid porous microspheres
Yue MA ; Shiyu TAN ; Feiyang CHU ; Zhuoqi CHEN ; Siyu LIU ; Wenshuai LIU ; Xia LIU
Chinese Journal of Tissue Engineering Research 2025;29(22):4653-4662
BACKGROUND:The proliferation and phenotypic maintenance of chondrocytes are limited under two-dimensional culture conditions.Porous microspheres serve as scaffolds,providing a three-dimensional culture environment that better mimics in vivo growth conditions.Stromal cell derived factor-1,a homeostatic cytokine with potent chemotactic effects,facilitates cell adhesion and proliferation.OBJECTIVE:To investigate the impact of stromal cell derived factor-1 grafted poly-L-lactic acid porous microspheres on the biological characteristics of chondrocytes and the formation of cartilage tissue.METHODS:(1)The effects of different concentrations of stromal cell derived factor-1 on rabbit chondrocyte proliferation,migration,and phenotypic maintenance were investigated in an in vitro setting.(2)Poly-L-lactic acid porous microspheres were prepared by double emulsion method.Stromal cell derived factor-1 was grafted onto poly-L-lactic acid porous microspheres through carbodiimide reaction.The grafting was verified by enzyme-linked immunosorbent assay and incubation with stromal cell derived factor-1-specific fluorescent antibodies.(3)Rabbit chondrocytes were inoculated on poly-L-lactic acid porous microspheres and grafted on stromal cell derived factor-1 poly-L-lactic acid porous microspheres to detect cell proliferation and adhesion.(4)The methylacrylamide-gelatin-chondrocyte complex(control group),poly-L-lactic acid porous microsphere-methylacrylamide-gelatin-chondrocyte complex(porous microsphere group),and grafted stromal cell derived factor-1 poly-L-lactic acid porous microsphere-methylacrylamide-gelatin-chondrocyte complex(porous microsphere modified group)were implanted under the skin of the back of nude mice,respectively.Samples were collected 8 weeks later and detected using histological staining and qRT-PCR for chondroblast related genes.RESULTS AND CONCLUSION:(1)Compared with 0 and 1 000 ng/mL stromal cell derived factor-1,1 and 500 ng/mL stromal cell derived factor 1 could promote the proliferation and migration of chondrocytes,and enhance the mRNA expression levels of type Ⅱ collagen,elastin,proliferating cell nuclear antigen,and Bcl-2 in chondrocytes.(2)Stromal cell derived factor-1 was successfully grafted onto poly-L-lactic acid porous microspheres with a grafting rate of 93.75%.(3)Compared with poly-L-lactic acid porous microspheres,grafted stromal cell derived factor-1 poly-L-lactic acid porous microspheres promoted the proliferation and adhesion of chondrocytes.(4)After 8 weeks of subcutaneous implantation in nude mice,compared with the control group and the porous microsphere group,the porous microsphere modified group had clearer cartilage lacunae structure,more chondro-specific matrix and type Ⅱ collagen deposition,and increased expression of elastin,type Ⅱ collagen,proliferating cell nuclear antigen,and Bcl-2 mRNA.These findings indicate that stromal cell derived factor-1 grafted poly-L-lactic acid porous microspheres are beneficial to chondrocyte adhesion,proliferation,phenotypic maintenance,and the formation of cartilage tissue in vivo.
8.Research progress of magnesium-based biomaterials in the treatment of bone defects induced by osteosarcoma
Jingteng CHEN ; Ling YU ; Shiyu LI ; Weichun GUO
Chinese Journal of Orthopaedics 2025;45(2):109-118
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents with a peak incidence between the ages of 10 and 20. It has an extremely high mortality and disability rate. In adults, osteosarcoma is the third most common bone tumor. Despite the advances in chemotherapy, surgical techniques, and radiotherapy that have significantly improved the overall survival rate of osteosarcoma, the long-term prognosis of patients has not shown substantial improvement, especially in cases of tumor metastasis and recurrence. Due to the highly invasive growth of tumor cells, the progression of osteosarcoma is often accompanied by the destruction of surrounding bone tissue and the formation of immature new bone, making treatment challenging, especially in tissue repair and functional recovery following surgical resection. Tumor resection surgery often results in extensive bone loss, particularly in cases involving joints or weight-bearing areas, making the reconstruction of bone structure and function highly complex. Currently, inert materials such as stainless steel or titanium alloy prostheses used in clinical practice exhibit poor biocompatibility and high elastic modulus, often leading to prosthesis loosening and infection. There is an urgent clinical need for multifunctional biomaterials capable of both repairing bone defects and inhibiting tumor recurrence. Magnesium-based biomaterials have shown excellent biodegradability and bioactivity, and the release of magnesium ions and degradation products effectively promotes bone tissue regeneration while demonstrating potential antitumor effects. This paper reviews the application of magnesium-based biomaterials in the treatment of bone defects associated with osteosarcoma, including their adaptation to the acidic conditions of the osteosarcoma microenvironment, their potential to promote osteogenesis, and their antitumor mechanisms. It also analyzes the mechanical compatibility of magnesium-based materials and the use of coating technologies to enhance their corrosion resistance, and explores the prospects of various types of magnesium-based compounds in the treatment of osteosarcoma-related bone defects.
9.Surveillance for Aedes albopictus in Guangzhou City from 2021 to 2023
Jinhua ZHOU ; Shiyu HE ; Tong LIU ; Zhifei CHENG ; Xiaoning LI ; Yimin JIANG ; Xueying LIANG ; Zongqiu CHEN ; Pengzhe QIN
Chinese Journal of Schistosomiasis Control 2025;37(1):76-80
Objective To investigate the population density and seasonal fluctuations of Aedes albopictus in Guangzhou City, Guangdong Province, from 2021 to 2023, so as to provide insights into A. albopictus control and management of dengue fever. Methods The surveillance of A. albopictus density was performed in all surveillance sites assigned across all streets (townships) in Guangzhou City during the period from January to December from 2021 to 2023. The surveillance frequency was twice every half month from May to September, and once every month for the rest of a year. In each surveillance period, A. albopictus mosquito larvae were captured from indoor and outdoor small water containers in residential areas, parks, medical facilities, schools, other government sectors and social organizations, construction sites, special industries and others for mosquito species identification. Adult mosquitoes were captured using electric mosquito suction apparatus for species identification and gender classification. Adult mosquitoes and mosquito eggs were collected with mosquito and egg traps at the breeding and dwelling places of Aedes mosquitoes for identification. The mosquito oviposition index (MOI), Breteau index (BI), adult mosquito density index (ADI) and standard space index (SSI) were calculated. The A. albopictus density was classified into grades 0, 1, 2 and 3 in each surveillance site, with Grade 0 density defined eligible, and the eligible rate of A. albopictus density was calculated at all surveillance sites each year from 2021 to 2023. In addition, the changing trends in MOI, SSI, BI and ADI of A. albopictus were analyzed in Guangzhou City from 2021 to 2023. Results The eligible rates of A. albopictus density were 61.69%, 68.75% and 55.15% in surveillance sites of Guangzhou City from 2021 to 2023 (χ2 = 297.712, P < 0.001), and appeared a tendency towards a reduction followed by a rise each year, which gradually reduced since January, maintained at a low level during the period between May and October, and gradually increased from November to December. The MOI, SSI, BI and ADI of A. albopictus all appeared a tendency towards a rise followed by a reduction in Guangzhou City during the period between January and December from 2021 to 2023. The BI of A. albopictus peaked in the first half of June in 2021 (4.03), the first half of July in 2022 (3.89) and the last half of August in 2023 (5.02), and the SSI of A. albopictus peaked in the last half of June in 2021 (0.93), the last half of May in 2022 (0.59), and the last half of June (0.94) and the first half of September in 2023 (1.12). In addition, the MOI of A. albopictus peaked in the first half of May in 2021 (8.64), the first half of June in 2022 (8.96), and the last half of May (10.21) and the last half of June in 2023 (10.89), and the ADI of A. albopictus peaked in the first half of June in 2021 (3.41), the last half of June in 2022 (4.06), and the first half of July in 2023 (3.61). Conclusions The density of A. albopictus is high in Guangzhou City during the period from May to October, and the risk of local outbreak caused by imported dengue fever is high. Persistent intensified surveillance of the density and seasonal fluctuation of A. albopictus is recommended and timely mosquito prevention and control is required according to the fluctuation in the A. albopictus density.
10.Expression of serpin family E member 1 in gastric cancer and its mechanisms in promoting gastric cancer
Yongyu CHEN ; Yiren HUANG ; Zheyi CHEN ; Bingqian ZHOU ; Shiyu CHEN ; Yingxia ZHENG
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(2):150-160
Objective·To investigate the expression of serpin family E member 1(SERPINE1)in gastric cancer and its potential mechanisms in promoting gastric cancer.Methods·Pan-cancer analysis of SERPINE1 was performed by using the TIMER2.0 online website,and the differences in the expression of SERPINE1 in samples with different tumor stages of gastric cancer were analysed by the clinical data of gastric cancer from The Cancer Genome Atlas(TCGA)database.Survival curves were plotted.Quantitative real-time PCR(qRT-PCR)was used to detect mRNA expression in paired samples of clinical gastric cancer tissues.The small interfering RNA(siRNA)transfection technique was used to knock down the expression of SERPINE1 in MGC-803 and SGC-7901 gastric cancer cell lines,and the migration and invasive abilities of gastric cancer cells were investigated by Transwell and invasion chamber experiments.The effects of SERPINE1 knockdown on the angiogenesis of gastric cancer cells were further explored by the migration assay of human umbilical vein endothelial cells(HUVEC)and tubule formation assay of HUVECs.The Gene Expression Omnibus(GEO)dataset was used for differential gene analysis in high and low expression groups based on the median value of SERPINE1 expression.The differentially expressed genes were further analyzed by Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis and Gene Set Enrichment Analysis(GSEA).qRT-PCR was performed to verify the expression levels of key genes related to epithelial-mesenchymal transition(EMT)and angiogenesis.Results·Bioinformatics analysis showed that SERPINE1 was highly overexpressed in a variety of primary tumour tissues,including gastric cancer.SERPINE1 gene expression increased with increasing tumour stage(P<0.001),and increased expression of SERPINE1 was associated with poor prognosis of gastric cancer(P<0.001).qRT-PCR results showed that SERPINE1 was significantly highly expressed in gastric cancer tissues(P=0.038).After knocking down SERPINE1,gastric cancer cell lines MGC-803 and SGC-7901 cells had decreased migration and invasion(P<0.05).Gastric cancer culture supernatants from the SERPINE1-knockdown gastric cancer cell line reduced angiogenesis in HUVECs(P<0.05).Differential genes in gastric cancer patients in the SERPINE1 high-expression group in the GEO database were enriched in cancer-related pathways such as focal adhesion,extracellular matrix receptor interaction,and angiogenesis-related pathways like angiogenesis and the vascular endothelial growth factor(VEGF)signalling pathway.The expression of SERPINE1 was negatively correlated with cadherin 1(CDH1),and positively correlated with other key genes related to EMT and angiogenesis.Moreover,the expression levels of key genes related to EMT and angiogenesis detected by qRT-PCR in SERPINE1 knockdown gastric cancer cell lines(P<0.05),were consistent with the correlation analysis results mentioned above.Conclusion·SERPINE1 expression is elevated in gastric cancer tissues,which could regulate the expression levels of key genes related to EMT and angiogenesis to promote the migration,invasion and angiogenesis of gastric cancer cells.


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