1.Modified Maimendong Decoction Inhibits Lung Cancer Metastasis by Up-Regulating Levels of NK and CD8+ T Cells in Peripheral Blood and Tumor Microenvironment
Zhipeng ZHANG ; Jianhui TIAN ; Zujun QUE ; Ziqi CHEN ; Bin LUO ; Shihui LIU
Cancer Research on Prevention and Treatment 2025;52(6):466-473
Objective To explore the mechanism of modified maimendong decoction (MMD) in inhibiting lung cancer metastasis from the perspective of immune regulation. Methods CTC-TJH-01 and LLC cells were intervened with different concentrations of modified maimendong decoction. The cell proliferation was detected with a CCK-8 kit, apoptosis was detected with an Annexin V-FITC/PI kit, and cell migration was detected through Transwell assays. A lung metastasis model was established through the tail vein injection of LLC cells into C57BL/6 mice, and body weight change and lung tumor metastasis in the mice were evaluated after continuous gavage intervention with MMD. HE staining, immunohistochemistry, and immunofluorescence were employed to observe the histomorphology, Ki-67 protein level, and NK and T cell levels of metastatic lesions. The levels of NK and T cells in the peripheral blood of mice were detected throughflow cytometry. Results MMD had no significant inhibitory effect on the proliferation, apoptosis, and migration of CTC-TJH-01 and LLC cells in vitro. In mice, MMD could significantly inhibit the lung metastasis of LLC cells, increase the proportion of NK and CD8+ T cells in peripheral blood and tumor microenvironment (P<0.05), and reduce the expression of Ki-67 protein in metastatic tumor tissues (P<0.05). Conclusion MMD may inhibit the growth of metastatic tumors by upregulating the expression levels of NK and CD8+ T cells in peripheral blood to promote the elimination of circulating tumor cells, and regulating the infiltration of NK and CD8+ T cells in the immune microenvironment of metastatic tumors, then play an antimetastatic role in lung cancer.
2.Effect of lncRNA MANCR on Proliferation, Migration, and Epithelial Mesenchymal Transition of Gastric Cancer Cells by Regulating miR-150-5p/GPNMB Axis
Chao LI ; Shihui WANG ; Jie LIN ; Fanke WANG ; Rui ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):135-142
ObjectiveTo investigate the effects of mitotically-associated long non-coding RNA (lncRNA MANCR) on the proliferation,migration, and epithelial mesenchymal transition (EMT) of gastric cancer (GC) cells by regulating the microRNA-50-5p (miR-150-5p)/non-metastatic melanoprotein B (GPNMB) axis. MethodsThe mRNA expressions of lncRNA MANCR,miR-150-5p, and GPNMB in 42 cases of GC tissue and adjacent tissue resected during surgery in the First Hospital of Hebei Medical University from June 2022 to September 2023 were detected by Real-time PCR. Human gastric mucosal epithelial cells GES-1 and human GC cells BGC-823 were cultured in vitro, and their lncRNA MANCR expression was detected. BGC-823 cells were randomly separated into control group (routine culture),sh-NC group (with sh-NC transfected),sh-MANCR group (with sh-MANCR transfected),sh-MANCR + anti-NC group (with sh-MANCR and anti-NC both transfected),and sh-MANCR + anti-miR-150-5p group (with sh-MANCR and anti-miR-150-5p both transfected). The mRNA expressions of lncRNA MANCR,miR-150-5p, and GPNMB in the BGC-823 cells of all groups were analyzed. EdU staining was used to detect the proliferation of BGC-823 cells. Transwell assay was used to detect the migration and invasion of BGC-823 cells. The expressions of EMT-related proteins E-cadherin,N-cadherin,Vimentin, and GPNMB were detected by Western blot. The interactions between lncRNA MANCR and miR-150-5p and between miR-150-5p and GPNMB were analyzed by dual luciferase reporter assay. ResultsThe mRNA expressions of lncRNA MANCR and GPNMB in GC tissue were higher than those in adjacent tissue,and the expression of miR-150-5p was lower than that in adjacent tissue (P<0.05). Compared with that in GES-1,lncRNA MANCR expression in BGC-823 cells was increased (P<0.05). Compared with those in the sh-NC group and control group,the EdU-positive cell rate,migration number,invasion number,the mRNA expressions of lncRNA MANCR and GPNMB, and the expressions of protein,N-cadherin protein, and Vimentin protein in the BGC-823 cells in the sh-MANCR group were lower ,and the protein expressions of miR-150-5p and E-cadherin were higher (P<0.05). Compared with those in the sh-MANCR group and the sh-MANCR + anti-NC group,the protein expressions of miR-150-5p and E-cadherin in the sh-MANCR + anti-miR-150-5p group were decreased. The EdU-positive cell rate,migration number,invasion number,mRNA expressions of GPNMB, and expressions of protein,N-cadherin protein, and Vimentin protein were increased (P<0.05). lncRNA MANCR could target the negative regulation of miR-150-5p,and miR-150-5p could target the negative regulation of GPNMB. ConclusionKnockout of lncRNA MANCR can inhibit the proliferation,migration, and EMT of GC cells by regulating the miR-150-5p/GPNMB axis.
3.Effect of lncRNA MANCR on Proliferation, Migration, and Epithelial Mesenchymal Transition of Gastric Cancer Cells by Regulating miR-150-5p/GPNMB Axis
Chao LI ; Shihui WANG ; Jie LIN ; Fanke WANG ; Rui ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):135-142
ObjectiveTo investigate the effects of mitotically-associated long non-coding RNA (lncRNA MANCR) on the proliferation,migration, and epithelial mesenchymal transition (EMT) of gastric cancer (GC) cells by regulating the microRNA-50-5p (miR-150-5p)/non-metastatic melanoprotein B (GPNMB) axis. MethodsThe mRNA expressions of lncRNA MANCR,miR-150-5p, and GPNMB in 42 cases of GC tissue and adjacent tissue resected during surgery in the First Hospital of Hebei Medical University from June 2022 to September 2023 were detected by Real-time PCR. Human gastric mucosal epithelial cells GES-1 and human GC cells BGC-823 were cultured in vitro, and their lncRNA MANCR expression was detected. BGC-823 cells were randomly separated into control group (routine culture),sh-NC group (with sh-NC transfected),sh-MANCR group (with sh-MANCR transfected),sh-MANCR + anti-NC group (with sh-MANCR and anti-NC both transfected),and sh-MANCR + anti-miR-150-5p group (with sh-MANCR and anti-miR-150-5p both transfected). The mRNA expressions of lncRNA MANCR,miR-150-5p, and GPNMB in the BGC-823 cells of all groups were analyzed. EdU staining was used to detect the proliferation of BGC-823 cells. Transwell assay was used to detect the migration and invasion of BGC-823 cells. The expressions of EMT-related proteins E-cadherin,N-cadherin,Vimentin, and GPNMB were detected by Western blot. The interactions between lncRNA MANCR and miR-150-5p and between miR-150-5p and GPNMB were analyzed by dual luciferase reporter assay. ResultsThe mRNA expressions of lncRNA MANCR and GPNMB in GC tissue were higher than those in adjacent tissue,and the expression of miR-150-5p was lower than that in adjacent tissue (P<0.05). Compared with that in GES-1,lncRNA MANCR expression in BGC-823 cells was increased (P<0.05). Compared with those in the sh-NC group and control group,the EdU-positive cell rate,migration number,invasion number,the mRNA expressions of lncRNA MANCR and GPNMB, and the expressions of protein,N-cadherin protein, and Vimentin protein in the BGC-823 cells in the sh-MANCR group were lower ,and the protein expressions of miR-150-5p and E-cadherin were higher (P<0.05). Compared with those in the sh-MANCR group and the sh-MANCR + anti-NC group,the protein expressions of miR-150-5p and E-cadherin in the sh-MANCR + anti-miR-150-5p group were decreased. The EdU-positive cell rate,migration number,invasion number,mRNA expressions of GPNMB, and expressions of protein,N-cadherin protein, and Vimentin protein were increased (P<0.05). lncRNA MANCR could target the negative regulation of miR-150-5p,and miR-150-5p could target the negative regulation of GPNMB. ConclusionKnockout of lncRNA MANCR can inhibit the proliferation,migration, and EMT of GC cells by regulating the miR-150-5p/GPNMB axis.
4.circFSCN1 regulates malignant behaviors of gastric cancer MGC803 cells via the miR-429/GPNMB axis
LI Chao ; WANG Shihui ; LIN Jie ; WANG Fanke ; ZHANG Rui
Chinese Journal of Cancer Biotherapy 2025;31(8):831-838
[摘 要] 目的:探究环状RNA肌动蛋白束蛋白1(circFSCN1)调节miR-429/非转移性黑色素蛋白B(GPNMB)轴对胃癌细胞恶性生物学行为的影响及机制。方法:收集2022年9月至2023年9月期间在河北医科大学第一医院手术切除的54例胃癌组织及相应癌旁组织,用qPCR法检测胃癌组织中circFSCN1、miR-429和GPNMB mRNA的表达。常规培养胃癌细胞MGC803,将其分为对照组、sh-NC组、sh-circFSCN1组、sh-circFSCN1 + anti-NC组、sh-circFSCN1 + anti-miR-429组。qPCR法各组MGC803细胞中circFSCN1、miR-429和GPNMB mRNA的表达。CCK-8法、克隆形成实验、Transwell实验和流式细胞术分别检测各组MGC803细胞的增殖、迁移、侵袭和凋亡。免疫荧光法检测各组细胞中GPNMB蛋白的表达。WB法检测各组MGC803细胞中PCNA、MMP-2、GPNMB、cleaved caspase-3蛋白的表达。双萤光素酶报告基因实验和RNA结合蛋白免疫共沉淀(RIP)实验验证circFSCN1与miR-429和miR-429与GPNMB之间的结合调控关系。结果:circFSCN1、GPNMB mRNA在胃癌组织中均呈高表达(均P < 0.05),miR-429呈低表达(P < 0.05)。敲减circFSCN1可促进miR-429表达,抑制GPNMB mRNA表达,抑制miR-429则可促进GPNMB mRNA表达。敲减circFSCN1可显著抑制MGC803细胞的增殖、迁移、侵袭能力,并促进其凋亡,抑制miR-429可部分逆转敲减circFSCN1的作用。敲减circFSCN1可抑制MGC803细胞中PCNA、MMP-2和GPNMB蛋白表达,抑制cleaved caspase-3蛋白表达,抑制miR-429可部分逆转敲减circFSCN1的作用。circFSCN1与miR-429和miR-429与GPNMB mRNA之间存在靶向结合负向调控关系。结论:敲减circFSCN1通过miR-429/GPNMB轴抑制胃癌细胞的恶性生物学行为,circFSCN1是胃癌潜在的治疗靶点。
5.Effects of LINC00894 regulating miR-205-5p/GPNMB axis on proliferation, migration, and invasion of gastric cancer cells
LI Chao ; WANG Shihui ; LIN Jie ; WANG Fanke ; ZHANG Rui
Chinese Journal of Cancer Biotherapy 2025;32(9):912-919
[摘 要] 目的:探究长链非编码RNA00894(LINC00894)调节微小RNA-205-5p(miR-205-5p)/糖蛋白非转移性黑色素瘤蛋白B(GPNMB)轴对胃癌细胞恶性生物学行为的影响。方法:收集2022年11月至2023年9月在河北医科大学第一医院手术切除的25例胃癌组织及相应癌旁组织,常规培养BGC823细胞,随机将其分为对照组、sh-NC组、sh-LINC00894组、sh-LINC00894 + anti-NC组、sh-LINC00894 + anti-miR-205-5p组,用转染试剂将相应质粒转染至各组细胞中。qPCR法检测各组BGC823细胞和癌组织中LINC00894、miR-205-5p和GPNMB mRNA表达,双萤光素酶报告基因实验和AGO2-RNA免疫共沉淀验证LINC00894与miR-205-5P和miR-205-5p与GPNMB间的靶向结合关系。克隆形成实验、EdU染色、划痕愈合实验和Transwell实验分别检测各组细胞的增殖、迁移和侵袭能力。WB法检测各组细胞中CDK1、MMP-2和MMP-9蛋白的表达。裸鼠移植瘤实验检测敲减LINC00894对移植瘤生长的影响,免疫组化法检测移植瘤组织中GPNMB蛋白的表达。结果:胃癌组织和细胞中LINC00894、GPNMB呈高表达,miR-205-5p呈低表达(均P < 0.05)。LINC00894与miR-205-5p和miR-205-5p与GPNMB之间存在靶向结合负向调控关系(均P < 0.05)。敲减LINC00894可促进BGC823细胞中miR-205-5p表达并抑制GPNMB表达(均P < 0.05),敲减LINC00894可抑制BGC823细胞的增殖、迁移和侵袭能力,以及抑制CDK1、MMP-2和MMP-9蛋白的表达(均P < 0.05),抑制miR-205-5p则可逆转此作用(均P < 0.05)。敲减LINC00894可抑制BGC823细胞移植瘤的生长、促进miR-205-5p表达、抑制GPNMB蛋白表达(均P < 0.05)。结论:在胃癌组织及细胞中LINC00894呈高表达,miR-205-5p呈低表达,敲减LINC00894表达可调控BGC823细胞中miR-205-5p/GPNMB通路蛋白表达并抑制其恶性生物学行为。
6.Value of alkaline phosphatase level after ursodeoxycholic acid treatment for one month and baseline red blood cell distribution width in predicting the treatment response of primary biliary cholangitis
Nan WANG ; Rong HU ; Shihui BIAN ; Wei ZHONG ; Pengfei ZHANG ; Youwen TAN
Journal of Clinical Hepatology 2024;40(3):496-501
ObjectiveTo investigate the value of baseline red cell distribution width (RDW) and alkaline phosphatase (ALP) level after ursodeoxycholic acid (UDCA) treatment for one month in predicting the response to UDCA treatment in patients with primary biliary cholangitis (PBC). MethodsA retrospective analysis was performed for the data of 127 patients with PBC who were diagnosed in Department of Hepatology, The Third People’s Hospital of Jiangsu University, from January 2015 to July 2022, with data collected at baseline, after one month of treatment, and after one year of follow-up. Based on the Paris-I criteria, the patients were divided into good response group and poor response group, and the two groups were analyzed in terms of clinical and laboratory features and their association with response to UDCA. The Logistic regression method was used to investigate the independent risk factors for response to UDCA treatment. The area under the ROC curve (AUC) was used to determine the optimal cut-off values of related indicators; the patients were divided into two groups based on such values, and the two groups were compared in terms of baseline indicators and response. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. ResultsCompared with the good response group, the poor response group had significantly higher levels of total bilirubin, aspartate aminotransferase/alanine aminotransferase, ALP, RDW, and RDW-CV at baseline and a significantly higher level of ALP after one month of UDCA treatment (Z=-4.792, -3.697, -2.399, -4.102, -3.220, and -4.236, all P<0.05). Compared with the good response group, the poor response group had significantly lower levels of albumin, hemoglobin, lymphocytes, hematocrit, and body mass index at baseline (Z=-3.592, -3.603, -2.602, -3.829, -2.432, all P<0.05), as well as significantly lower levels of prealbumin, albumin/globulin ratio, apolipoprotein A, and free triiodothyronine at baseline (t=4.530, 3.402, 3.485, and 3.639, all P<0.001). Compared with the poor response group, the good response group had a significantly lower proportion of patients with liver cirrhosis, gallstones/cholecystitis, or anemia (χ2=20.815, 3.892, and 12.283, all P<0.05). Baseline RDW (odds ratio [OR]=1.157, 95% confidence interval [CI]: 1.028 — 1.301, P=0.015) and ALP level after one month of treatment (OR=1.012, 95%CI: 1.005 — 1.020, P=0.002) were independent risk factors for response to UDCA, with an AUC of 0.713 and 0.720, respectively. The patients with baseline RDW≥upper limit of normal (ULN) and ALP≥2.2×ULN after one month of UDCA treatment had a lower UDCA response rate (42.6% vs 8.2%, χ2=20.813, P<0.001). ConclusionPatients with baseline RDW≥ULN and ALP≥2.2×ULN after one month of UDCA treatment tend to have a low biochemical response rate to UDCA.
7.Determination of medical fault for orthopedic missed diagnoses--Taking 35 adjudication documents as an example
Shuang ZHAO ; Wei CHEN ; Shihui LIU ; Meng ZHANG
Chinese Journal of Forensic Medicine 2024;39(3):273-277
Thirty-five cases of medical damage liability disputes concerning orthopedic omission of diagnosis that were made public in the China Judgement and Documentation Network during 2021—2023 were analyzed.The basic situation of the cases,appraisal opinions,liability composition,damage consequences,and causes of omission of diagnosis are analyzed,statistical results are obtained,and the results are discussed and relevant suggestions are made.
8.Ergonomics methodology,application framework and research prospect for unmanned aerial vehicle lifecycle
Shihui ZHANG ; Guichao SHI ; Chuanyan FENG ; Kun JI
Space Medicine & Medical Engineering 2024;35(3):180-186
With the rapid growth of the utilization of Unmanned Aerial Vehicle(UAV),the corresponding ergonomics problems are becoming increasingly prominent.Based on a review of the literature and industrial practice,ergonomics evaluation methods for UAV lifecycle are investigated in this study.The ergonomics research scope of UAV and the ergonomics evaluation method of UAV lifecycle are emphasized;The ergonomics analysis framework of UAV lifecycle is proposed,and the ergonomics practice method under key lifecycle stage of UAV development for typical applications is explained;In addition,combined with the development of intelligent technology,the research prospect of ergonomics on UAV is put forward.This study can provide some reference for the development of UAV from the perspective of ergonomics design and evaluation.
9.Calcium-binding protein S100A4 regulates glioma cell proliferation,survival and migration functions through TLR4/NF-κB signaling pathway
Dingshan ZHANG ; Tian TAO ; Shihui MO ; Tongqian WU ; Jingjing HE ; Fang YU
Chinese Journal of Immunology 2024;40(5):910-917
Objective:To investigate the effects and mechanisms of exogenous calcium-binding protein S100A4 on prolifera-tion,survival and migration functions of glioma cells.Methods:Pan-cancer dataset was downloaded from UCSC database for the analysis of S100A4 expression and prognosis in pan-cancer,and transcriptome and clinical data of glioma patients were downloaded from CGGA database.Prognosis and progression of S100A4 expression in glioma patients were analyzed by R software.S100A4 protein network interaction of glioma patients were addressed by online analytical tools GEPIA and STRING.Human glioma cell lines(U87 and U251)were cultured in vitro,and the experiment was divided into 3 groups:PBS group,S100A4 group and S100A4+TAK242 group[Resa-torvid(TAK242)was a specific inhibitor of Toll-like receptors 4(TLR4)].Flow cytometry was used to detect proliferation and apopto-sis of glioma cells.Wound healing assay,Transwell assay and clone formation assay were used to detect migration and proliferation ability of U87 and U251 cells,and Western blot was used to detect levels of TLR4 protein and NF-κB related signaling proteins.Results:Bioinformatics results showed that S100A4 was significantly upregulated in multiple tumours(P<0.05),which included glio-blastoma(GBM),lower grade glioma(LGG),stomach adenocarcinoma(STAD),liver hepatocellular carcinoma(LIHC),etc,with poorer prognosis in GBM and LGG.Compared with glioma patients with low expression of S1004,high expression S100A4 in glioma patients had shorter survival and higher degree of WHO classification.In addition,S100A4 protein in glioma patients may interact with Annexin A2(ANXA2),TLR4 and advanced glycosylation end product-specific receptor(AGER)proteins.In cellular experiments,U87 and U251 cells showed enhanced proliferation and migration,and significantly up-regulated levels of TLR4,p-ERK1/2,p-p38 and p-p65 proteins after exogenous S100A4 treatment compared to PBS group(P<0.05),while glioma cells in S100A4+TAK242 group showed weaker proliferation and migration,and lower TLR4,p-p38 and p-p65 protein levels than those in S100A4 group,TLR4,p-ERK1/2,p-p38,p-p65 protein levels were significantly down-regulated(P<0.05).Conclusion:S100A4 may regulate func-tion of glioma proliferation,migration and survival through TLR4/NF-κB signaling pathway.
10.Visual analysis of the role of neutrophils in diabetes based on CiteSpace
Jinxi WANG ; Rong YU ; Juan HUANG ; Yangyang LIU ; Tiantian ZHANG ; Chun GUO ; Wei LI ; Hui YANG ; Shihui LEI
Chinese Journal of Comparative Medicine 2024;34(6):28-39
Objective Th is aim of this review was to clarify the role of neutrophils in diabetes by summarizing the characterization studies,potential trends,and research hotspots relating to neutrophils in the diabetes research field.Methods 2998 relevant studies on neutrophils in the diabetes research field indexed in Web of Science from 2010 to 2023 were retrieved,and a visual analysis of the relevant literature was conducted using CiteSpace 6.1.R6.Results Since 2012,the number of publications on this topic has grown rapidly.Bayat Mohammad,Liu Tong,Amini Abdollah,and Zhang Rui are high-yield authors,with seven related articles published.China and Shanghai Jiao Tong University are the country and institution with the most published papers.The most influential journal in this field is"Nature Medicine".Literature co-citation analysis of topics related to diabetes showed that the greatest focus is currently on"extracellular trap"and"COVID-19 patient".Co-occurrence analysis,clustering analysis,and keyword burst analysis indicated that"lymphocyte ratio"(13.08)and"neutrophil extracellular trap"(7.2)are the most researched topics in the field of neutrophils and diabetes.Literature in this field mainly focuses on"myocardial infarction","endothelial","oxidative stress",and"apoptosis".Conclusions This article highlights the evolving trends in research into neutrophils in the diabetes field using CiteSpace,providing new insights for researchers aiming to conduct research in this area.

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