1.Compound Xishu Granules Inhibit Proliferation of Hepatocellular Carcinoma Cells by Regulating Ferroptosis
Yuan TIAN ; Yuxi WANG ; Zhen LIU ; Yuncheng MA ; Hongyu ZHU ; Xiaozhu WANG ; Qian LI ; Jian GAO ; Weiling WANG ; Wenhui XU ; Ting WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):37-45
ObjectiveTo study the mechanism of compound Xishu granules (CXG) in inhibiting the proliferation of hepatocellular carcinoma cells by regulating ferroptosis. MethodsThe transplanted tumor model of human Huh7 was established with nude mice and the successfully modeled mice were randomized into model, Fufang Banmao (0.21 g·kg-1), low-dose (1.87 g·kg-1) CXG, medium-dose (3.74 g·kg-1) CXG, and high-dose (7.49 g·kg-1) CXG groups. Mice were administrated with drinking water or CXG for 28 days, and the body weight and tumor volume were measured every 4 days. Hematoxylin-eosin staining was employed to observe the histopathological changes of tumors. The cell-counting kit-8 (CCK-8) was used to examine the survival rate of Huh7 cells treated with different concentrations (0, 31.25, 62.5, 125, 250, 500, 1 000 mg·L-1) of CXG for 24 h and 48 h. CA-AM, DCFH-DA, and C11-BODIPY581/591 fluorescent probes were used to determine the intracellular levels of ferrous ion (Fe2+), reactive oxygen species (ROS), and lipid peroxide (LPO), respectively. The colorimetric method was employed to measure the levels of glutathione (GSH) and superoxide dismutase (SOD). Western blot was employed to determine the protein levels of glutathione peroxidase 4 (GPX4), transferrin receptor 1 (TFR1), and ferritin heavy chain 1 (FTH1), respectively. ResultsIn the animal experiment, compared with the model group, the drug treatment groups showed reductions in the tumor volume from day 12 (P<0.01). After treatment, the Fufang Banmao and low-, medium-, and high-dose CXG groups had lower tumor volume, relative tumor volume, and tumor weight than the model group (P<0.05), with tumor inhibition rates of 48.99%, 79.93%, 91.38%, and 97.36%, respectively. Moreover, the CXG groups had lower tumor volume and relative tumor volume (P<0.05 in all the three dose groups) and lower tumor weight (P<0.05 in medium-dose and high-dose groups) than the Fufang Banmao group. Compared with the model group, the drug treatment groups showed reduced number of tumor cells, necrotic foci with karyopyknosis, nuclear fragmentation, and nucleolysis, and the high-dose CXG group showed an increase in the proportion of interstitial fibroblasts. In the cell experiment, compared with the blank group, CXG reduced the survival rate of Huh7 cells in a dose-dependent manner after incubation for 24 h and 48 h (P<0.05). Compared with the blank group, the RSL3 group and the low-, medium-, and high-dose CXG groups showed a decrease in the relative fluorescence intensity of CA-AM and increases in the fluorescence intensity of DCFH-DA and fluorescence ratio of C11-BODIPY581/591, which indicated elevations in the levels of Fe2+ (P<0.01), ROS (P<0.05), and LPO (P<0.01), respectively. Compared with the blank group, the RSL3 and low-, medium-, and high-dose CXG groups showed lowered levels of GSH and SOD (P<0.05). In addition, the RSL3 group and the medium- and high-dose CXG groups showed down-regulated expression of GPX4 and FTH1 (P<0.05), and the low- and high-dose CXG groups presented up-regulated expression of TFR1 (P<0.05). ConclusionCXG suppresses the proliferation of hepatocellular carcinoma cells by inducing ferroptosis via downregulating the GSH-GPX4 signaling axis and increasing intracellular Fe2+and LPO levels.
2.Transplacental digoxin treatment for fetal supraventricular arrhythmias: Insights from Chinese fetuses.
Chuan WANG ; Li ZHAO ; Shuran SHAO ; Haiyan YU ; Shu ZHOU ; Yifei LI ; Qi ZHU ; Xiaoliang LIU ; Hongyu DUAN ; Hanmin LIU ; Yimin HUA ; Kaiyu ZHOU
Chinese Medical Journal 2025;138(12):1499-1501
3.Sangma Zhike Formula alleviates airway inflammation and hyperresponsiveness in rats with postinfectious cough by inhibiting the TRPV1-SP/CGRP and pyroptosis pathways.
Qinjun YANG ; Hongyu ZHU ; Yuan GAO ; Cheng YANG ; Tong LIU ; Lu ZHANG ; Jiabing TONG ; Zegeng LI
Journal of Southern Medical University 2025;45(9):1830-1839
OBJECTIVES:
To investigate the therapeutic mechanism of Sangma Zhike Formula (SMZKF) for relieving cough sensitivity and airway inflammation in rats with postinfectious cough (PIC).
METHODS:
Male SD rat models were established by cigarette smoke exposure with intranasal LPS instillation and capsaicin aerosol inhalation. From day 19 following the start of PIC modeling, the rats received daily treatment with saline (model group), low-, medium-, and high-dose SMZKF, and compound methoxyphenamine (ASM) via gavage for 10 consecutive days (n=8). The assessments included behavioral changes, cough sensitivity (latency and frequency), lung histopathology, inflammatory cell counts and cytokine/mediator levels in the bronchoalveolar lavage fluid (BALF), oxidative stress markers in the lung tissue, and expressions of proteins related with cough hypersensitivity and pyroptosis.
RESULTS:
The rat models of PIC exhibited reduced mental alertness, accelerated respiration, and pronounced symptoms such as coughing, sneezing, and facial scratching with significantly shortened cough latency and increased 5-min cough frequency. Histopathological analysis revealed collapsed alveolar structures, thickened alveolar septa, and extensive inflammatory cell infiltration in the bronchi and peribronchial regions, accompanied by elevated bronchial and alveolar inflammation scores of the rat models. In the BALF, inflammatory cell counts and the levels of IL-1β, TNF-α, IL-6, COX-2, PGE-2, and TXA-2 were all markedly elevated, and the pulmonary oxidative stress markers (ROS and MDA) and myeloperoxidase (MPO) activity were also significantly increased. The pulmonary expressions of cough hypersensitivity-related proteins (TRPV1, SP, CGRP, and NK1R) and pyroptosis-associated markers (P-NF-κB, NLRP3, ACS, cleaved caspase-1, cleaved IL-1β, and GSDMD-N) were significantly upregulated in the model group. SMZKF interventions significantly ameliorated these pathological changes in the rat models, and high-dose SMZKF produced a similar therapeutic efficacy to that of ASM.
CONCLUSIONS
SMZKF alleviates cough sensitivity and airway inflammation in PIC rats possibly by inhibiting TRPV1-mediated SP/NK1R signaling and the NLRP3/caspase-1/GSDMD pyroptosis pathway.
Animals
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Cough/metabolism*
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Rats, Sprague-Dawley
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Pyroptosis/drug effects*
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Male
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TRPV Cation Channels/metabolism*
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Rats
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Drugs, Chinese Herbal/pharmacology*
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Inflammation
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Signal Transduction
4.Expert consensus on the diagnosis and treatment of cemental tear.
Ye LIANG ; Hongrui LIU ; Chengjia XIE ; Yang YU ; Jinlong SHAO ; Chunxu LV ; Wenyan KANG ; Fuhua YAN ; Yaping PAN ; Faming CHEN ; Yan XU ; Zuomin WANG ; Yao SUN ; Ang LI ; Lili CHEN ; Qingxian LUAN ; Chuanjiang ZHAO ; Zhengguo CAO ; Yi LIU ; Jiang SUN ; Zhongchen SONG ; Lei ZHAO ; Li LIN ; Peihui DING ; Weilian SUN ; Jun WANG ; Jiang LIN ; Guangxun ZHU ; Qi ZHANG ; Lijun LUO ; Jiayin DENG ; Yihuai PAN ; Jin ZHAO ; Aimei SONG ; Hongmei GUO ; Jin ZHANG ; Pingping CUI ; Song GE ; Rui ZHANG ; Xiuyun REN ; Shengbin HUANG ; Xi WEI ; Lihong QIU ; Jing DENG ; Keqing PAN ; Dandan MA ; Hongyu ZHAO ; Dong CHEN ; Liangjun ZHONG ; Gang DING ; Wu CHEN ; Quanchen XU ; Xiaoyu SUN ; Lingqian DU ; Ling LI ; Yijia WANG ; Xiaoyuan LI ; Qiang CHEN ; Hui WANG ; Zheng ZHANG ; Mengmeng LIU ; Chengfei ZHANG ; Xuedong ZHOU ; Shaohua GE
International Journal of Oral Science 2025;17(1):61-61
Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans
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Dental Cementum/injuries*
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Consensus
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Diagnosis, Differential
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Cone-Beam Computed Tomography
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Tooth Fractures/therapy*
5.One case of adrenal aldosterone-cortisol co-producing adenoma: clinical analysis and literature review
Zhiying BIAN ; Fei GAO ; Hongyu WANG ; Boyu ZHU ; Yi WANG ; Wenjuan QIU ; Jun AN ; Chun XU
Chinese Journal of Endocrine Surgery 2024;18(3):459-460
We will review a case of adrenal aldosterone-cortisol co-producing adenoma (A/CPA) admitted to our hospital on May 7, 2021. By reviewing the clinical courses of this case and its relevant literatures, we hope to improve the understanding and treatment level of this disease.
6.Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities.
Youtao XU ; Qinhong SUN ; Siwei WANG ; Hongyu ZHU ; Guozhang DONG ; Fanchen MENG ; Zhijun XIA ; Jing YOU ; Xiangru KONG ; Jintao WU ; Peng CHEN ; Fangwei YUAN ; Xinyu YU ; Jinfu JI ; Zhitong LI ; Pengcheng ZHU ; Yuxiang SUN ; Tongyan LIU ; Rong YIN ; Lin XU
Chinese Journal of Lung Cancer 2024;26(12):889-900
BACKGROUND:
In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration.
METHODS:
A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases.
RESULTS:
MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05).
CONCLUSIONS
The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans
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Lung Neoplasms/genetics*
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Adenocarcinoma of Lung/genetics*
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China
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Prognosis
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Transcription Factors
7.Effect of enriched environment combined with acupuncture at head points on behavior in rats with autism spectrum disorder
Zichen MU ; Qiang TANG ; Yunqiu SHI ; Yan WANG ; Shuwei ZHU ; Ya'nan ZHUANG ; Danshuang XU ; Hongyu LI ; Baolong LI ; Chunyan ZHANG ; Mengke YUAN
Chinese Journal of Rehabilitation Theory and Practice 2024;30(2):176-182
ObjectiveTo observe the effect of enriched environment (EE) combined with acupuncture at head point (HA) on behavior in rats with autism spectrum disorder. MethodsHealthy female Wistar rats were given peritoneal injection of sodium valproate at 12.5 days of gestation. Twenty-four male offspring rats were randomly selected and then randomly divided into model group (n = 6), EE group (n = 6), HA group (n = 6) and EE combined with HA group (the combined group, n = 6). Six male offspring rats born from female mice injected with the same amount of saline intraperitoneally were as control group. After four weeks of treatment, all the five groups were tested with three-chamber test and marble burying test, and the sociability index, the social novelty index and the number of buried marbles were recorded. The levels of interleukin (IL)-1β and IL-6 in peripheral blood were determined by enzyme-linked immunosorbent assay (ELISA). ResultsAfter treatment, compared with the model group, the sociability index and the social novelty index improved (P < 0.05), the number of buried marbles reduced (P < 0.05), and the levels of IL-6 and IL-1β in peripheral blood decreased in EE group, HA group and the combined group (P < 0.05); while the combined group was the best (P < 0.01). ConclusionBoth EE or acupuncture at HA could improve behavioral symptoms, and reduce the expression of inflammatory factors in rats with autism spectrum disorder. The combination of the two methods showed the best result.
8.Effectiveness of rhomboid intercostal and sub-serratus plane block in improving early recovery quality after thoracoscopic radical surgery for lung cancer
Qian HAO ; Hongyu DAI ; Chunyan LI ; Hongmei ZHOU ; Zhipeng ZHU
China Modern Doctor 2024;62(8):25-29
Objective Verify the improvement effect of rhomboid intercostal and sub-serratus plane block on the quality of early postoperative recovery in patients undergoing thoracoscopic radical resection of lung cancer;Comparison of the differences in the effect of regional block at different timing on improving the quality of early postoperative recovery.Methods A total of 75 patients,aged 18 to 75 years,with ASA gradeⅠ-Ⅱ,who were scheduled to undergo thoracoscopic radical resection of lung cancer from January 2022 to January 2023 were selected.Randomly divided into three groups:blank control group(Group C),preoperative block group(PR group),and postoperative block group(PO group).The PR group and the PO group received ultrasound guided rhomboid intercostal and sub-serratus plane block in the preoperative anesthesia preparation room and postoperative anesthesia recovery room,respectively,with a dosage of 0.375%ropivacaine 30ml.Evaluate the postoperative recovery quality of patients at 24 and 48 hours using the postoperative recovery quality rating scale(QoR-40)scoring scale.Record numeric rating scale(NRS)pain scores in resting and active states at 0.5h,1h,2h,4h,8h,12h,24h,and 48h after surgery.Record the consumption of opioid drugs during and after surgery,the effective number of postoperative patient-controlled intravenous analgesia(PCIA)compressions,and the incidence of nausea and vomiting.Results Compared with Group C,the consumption of opioids during surgery in the PR group was significantly reduced.The QoR-40 score at 24 hours after surgery was significantly higher in the PR and PO groups.Significant reduction in NRS scores between 1-8 hours of rest and 1-12 hours of activity after surgery,and the effective times of PCIA compressions and opioid consumption were significantly reduced(P<0.05).Compared with the PR group,the PO group consumed more opioids during surgery and had a higher NRS score at 0.5 hours after surgery(P<0.05).There was no significant difference in postoperative QoR-40 scores,PCIA effective compressions,and opioid consumption;There was no statistically significant difference in the incidence of postoperative nausea and vomiting among the three groups.Conclusion Rhomboid intercostal and sub-serratus plane block can improve the early recovery quality of patients undergoing thoracoscopic radical resection of lung cancer,reduce the postoperative pain level of patients,and reduce the amount of opioids used in perioperative period,and its effectiveness has nothing to do with the blocking time.
9.Clinical effect of procaterol hydrochloride combined with Xiaokechuan capsule in the treatment of cough variant asthma and its impact on serological indicators and airway function of children
Hemin ZHU ; Hongyu WANG ; Xiaoyan GUAN
Journal of Xinxiang Medical College 2024;41(1):60-64,70
Objective To explore the clinical effect of procaterol hydrochloride combined with Xiaokechuan capsule in the treatment of cough variant asthma(CVA)and its impact on serological indicators,airway function of children.Methods A total of 124 children with CVA admitted to the Zigong First People's Hospital from March 2019 to April 2022 were selected as the research subjects.The children were divided into control group and observation group according to random number table method,with 62 cases in each group.The children in the control group were treated with procaterol hydrochloride,and the children in the observation group were treated with procaterol hydrochloride and Xiaokechuan capsule for two weeks.The clinical efficacy of children was compared between the two groups after treatment.The cough scores during the day and night of children were evaluated in the two groups before and 2 weeks after treatment.The serum high mobility group protein B1(HMGB1),Toll like receptor 4(TLR4),nuclear factor-κB(NF-κB),interleukin-4(IL-4),interferon-γ(INF-γ)levels of children in the two groups were measured by enzyme linked immunosorbent assay before and 2 weeks after treatment,and the ratio of INF-γ/IL-was calculated.The 25%maximal expiratory flow-volume(MEF25),50%maximal expiratory flow-volume(MEF50),75%maximal expiratory flow-volume(MEF75)of children in the two groups were measured by lung function detector before and 2 weeks after treatment.The adverse reactions of children in the two groups were recorded during treatment.Results The total effective rate of children in the control group and observation group was 82.26%(51/62)and 95.16%(59/62),respectively;the total effective rate of children in the observation group was significantly higher than that in the control group(P<0.05).There was no significant difference in cough scores during the day and night of children between the two groups before treatment(P>0.05);the cough scores during the day and night of children after treatment were significantly lower than those before treatment in the two groups(P<0.05);after treatment,the cough scores during the day and night of children in the observation group were significantly lower than those in the control group(P<0.05).There was no significant difference in serum HMGB1,TLR4,NF-κB levels of children between the two groups before treatment(P>0.05);the serum HMGB1,TLR4,NF-κB levels of children after treatment were significantly lower than those before treatment in the two groups(P<0.05);after treatment,the serum levels of HMGB1,TLR4,and NF-κB of children in the observation group were significantly lower than those in the control group(P<0.05).There was no significant difference in MEF25,MEF50,and MEF75 of children between the two groups before treatment(P>0.05);the MEF25,MEF50,and MEF75 of children after treatment were significantly higher than those before treatment in the two groups(P<0.05);after treatment,the MEF25,MEF50,and MEF75 of children in the observation group were significantly higher than those in the control group(P<0.05).There was no significant difference in serum IL-4,INF-γ levels and the ratio of INF-γ/IL-4 of children between the two groups before treatment(P>0.05);the serum IL-4 level of children after treatment were significantly lower than those before treatment,the INF-γ level and the ratio of INF-γ/IL-4 were significantly higher than those before treatment in the two groups(P<0.05);after treatment,the serum IL-4 level of children in the observation group was significantly lower than that in the control group,the INF-γ level and the ratio of INF-γ/IL-4 were significantly higher than those in the control group(P<0.05).All children had good drug tolerance during the treatment period,and no significant adverse drug reactions were observed.Conclusion The combination of Xiaokechuan capsules and procaterol hydrochloride has a significant therapeutic effect for pediatric CVA,and its mechanism of action may be related to the regulation of HMGB1-TLR4-NF-κB signal pathway.
10.Identification and Analysis of SND1 as an Oncogene and Prognostic Biomarker for Lung Adenocarcinoma
ZHANG RUIHAO ; HUANG HUA ; ZHU GUANGSHENG ; WU DI ; CHEN CHEN ; CAO PEIJUN ; DING CHEN ; LIU HONGYU ; CHEN JUN ; LI YONGWEN
Chinese Journal of Lung Cancer 2024;27(1):25-37
Background and objective Transcription factor(TF)can bind specific sequences that either promotes or represses the transcription of target genes,and exerts important effects on tumorigenesis,migration,invasion.Staphylococcal nuclease-containing structural domain 1(SND1),which is a transcriptional co-activator,is considered as a promising target for tumor therapy.However,its role in lung adenocarcinoma(LUAD)remains unclear.This study aims to explore the role of SND1 in LUAD.Methods Data from The Cancer Genome Atlas(TCGA),Gene Expression Omnibus(GEO),Clinical Pro-teomic Tumor Analysis Consortium(CPTAC),and Human Protein Atlas(HPA)database was obtained to explore the associa-tion between SND1 and the prognosis,as well as the immune cell infiltration,and subcellular localization in LUAD tissues.Furthermore,the functional role of SND1 in LUAD was verified in vitro.EdU assay,CCK-8 assay,flow cytometry,scratch assay,Transwell assay and Western blot were performed.Results SND1 was found to be upregulated and high expression of SND1 is correlated with poor prognosis of LUAD patients.In addition,SND1 was predominantly present in the cytoplasm of LUAD cells.Enrichment analysis showed that SND1 was closely associated with the cell cycle,as well as DNA replication,and chro-mosome segregation.Immune infiltration analysis showed that SND1 was closely associated with various immune cell popula-tions,including T cells,B cells,cytotoxic cells and dendritic cells.In vitro studies demonstrated that silencing of SND1 inhib-ited cell proliferation,invasion and migration of LUAD cells.Besides,cell cycle was blocked at G,phase by down-regulating SND1.Conclusion SND1 might be an important prognostic biomarker of LUAD and may promote LUAD cells proliferation and migration.

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