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Phytoestrogen genistein decreases contractile response of aortic artery in vitro and arterial blood pressure in vivo

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Acta Pharmacologica Sinica 2004年第3期25卷 59-64页

作者： hong-fang li1,long-de wang2,song-yi qu department of physiology,lanzhou medical college,lanzhou 730000 2Affiliated Hospital,Gansu Chinese medical college,lanzhou 730020,China department of physiology Lanzhou Medical College Lanzhou 730000 Affiliated Hospital Gansu Chinese Medical College Lanzhou 730020

AIM: To determine the mechanisms of effects of phytoestrogen genistein on the contracted rabbit aortic arteries in vitro, and observe the effect of genistein and 17-β estradiol on mean arterial pressure (MAP) in ovariectomized (OVX) rats. METHODS: (1) Strips of rabbit aortic smooth muscle were suspended in organ baths containing Kreb’s solution, and then isometric tension was measured. (2) Female mature Wistar rats underwent a bilateral ovariectomy (OVX). Sham-operated rats (SHAM) were used as controls. After administration of genistein (0.4 mg·kg-1·d-1, sc), 17-β estradiol (1 mg·kg-1·d-1, sc) or theirvehicle sesame oil for 21 d,MAP was measured. RESULTS: (1) Similar to 17-β estradiol, genistein could dose-dependently relax 40 mmol/L KCl-precontracted arterial strips. Incubation with Nω-L-nitro-arginine (L-NNA), methylene blue (MB), indomethacin, propranolol or endothelium removal did not affect relaxation induced by genistein. In calcium-free solution containing 0.01mmol/L egtazic acid (EGTA), genistein inhibited not only the first phase contraction induced by noradrenaline (NA), but also the second contraction induced by CaCl2. In addition, genistein could reduce the contractile responses of NA, KCl and CaCl2, and shift their cumulative concentration-response curves rightward. (2) MAP in OVX rats was significantlyhigher compared with that of SHAM rats. However,after chronically treatment with genistein or 17-β estradiol for 21 d the baseline MAP in OVX rats was reduced significantly. CONCLUSIONS: (1) The vasodilator effect of genistein in vitro is endothelium independent and not related to the nitric oxide, its mechanisms being probably due to inhibition of Ca2+ influx through calcium channels in a noncompetitive manner and Ca2+ release from intracellular store induced by NA. (2) Administration of genistein or 17-β estradiol can chronically decrease MAP in OVX rats.

关键词： genistein aorta smooth muscle muscle relaxation calciumchannel vascular endothelium blood pressure

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Electroacupuncture at Sensitized Acupoints Relieves Somatic Referred Pain in Colitis Rats by Inhibiting Sympathetic-Sensory Coupling to Interferewith 5-HT Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第2期30卷 152-162页

作者： YANG ying qu Jin-yu GUO Hua ZHOU Hai-ying RUAN Xia PENG ying-chun SHEN Xue-fang XIONG Jin wang yi-li School of Clinical Medicine Chengdu Medical CollegeChengdu(610500)China department of Rehabilitation Medicine the First Affliated Hospital of Chengdu Medical CollegeChengdu(610500)China department of Rehabilitation Medicine West China HospitalSichuan University/West China School of NursingSichuan UniversityChengdu(610041)China department of Neurology the First Affiliated Hospital of Chengdu Medical CollegeChengdu(610500)China

Objective:To investigate whether electroacupuncture(EA) at sensitized acupoints could reduce sympathetic-sensory coupling(SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine(5-HT)ergic neural pathways to relieve colitis and somatic referred pain,and explore the underlying ***:Rats were treated with 5% dextran sodium sulfate(DSS) solution for 7 days to establish a colitis *** rats were randomly divided into the control and model groups according to a random number table(n=6).According to the Research on Rat Acupoint Atlas",sensitized acupoints and non-sensitized acupoints were *** were randomly divided into the control,model,Zusanli-EA(ST 36),Dachangshu-EA(BL 25),and Xinshu(BL 15) groups(n=6),as well as the control,model,EA,and EA+GR113808(a 5-HT inhibitor)groups(n=6).The rats in the control group received no *** was administered on 2 days after modeling using the stimulation pavameters:1 mA,2 Hz,for 30 min,with sparse and dense waves,for 14 consecutive ***113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive *** sensitivity was assessed with von Frey *** weight and disease activity index(DAI) scores of rats were *** and eosin staining was performed to observe colon *** was analyzed by immunofluorescence *** staining was performed to detect 5-HT and substance P(SP) *** calcitonin gene-related peptide(CGRP) in skin tissue and tyrosine hydroxylase(TH) protein levels in DRG were detected by Western *** levels of hyaluronic acid(HA),bradykinin(BK),prostaglandin I2(PGI2) in skin tissue,5-HT,tryptophan hydroxylase 1(TPH1),serotonin transporters(SERT),5-HT 3 receptor(5-HT3R),and 5-HT 4 receptor(5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay(EliSA).Results:BL 25 and ST 36 acupoints were determined as sensitized acupoints,and BL 1

关键词： electroacupuncture sensitized acupoints sympathetic-sensory coupling 5-hydroxytryptamine neurogenic inflammation somaticreferredpain

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Analysis of acupoint massage combined with touch on relieving anxiety and pain in patients with oral implant surgery

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World Journal of Psychiatry 2024年第4期14卷 533-540页

作者： Jin-hong qu Cheng-Cheng Shou Xin He Qin wang Yue-Xia fang department of Stomatology Hangzhou Lin'an Traditional Chinese Medicine HospitalHangzhou 311300Zhejiang ProvinceChina department of Software R&D Hangzhou Broadlink Technology CoLtd.Hangzhou 311300Zhejiang ProvinceChina department of Stomatology Hangzhou Red Cross HospitalHangzhou 310003Zhejiang ProvinceChina department of Cardiovascular Hangzhou Lin'an Traditional Chinese Medicine HospitalHangzhou 311300Zhejiang ProvinceChina department of Traditional Chinese Medicine development Hangzhou Lin'an Traditional Chinese Medicine HospitalHangzhou 311300Zhejiang ProvinceChina

BACKGROUND Oral implant surgery is an effective procedure for artificial implants in missing tooth areas under local *** patients under local anesthesia are conscious during this procedure,compared with general anesthesia-related operations,they are more likely to experience negative emotions,such as anxiety and *** emotional reactions result in shivering and chills in the limbs,leading to poor doctor-patient cooperation and even avoidance of *** traditional Chinese medicine,it is believed that acupoint massage regulates blood and Qi,dredge menstruation,and relieve pain,which is beneficial for patients’emotional adjustment;however,there are few related clinical *** To observe the changes in anxiety and pain in patients with oral implant after acupoint massage combined with touch *** One hundred patients undergoing oral implantation in our hospital between May 2020 and May 2023 were randomly divided into control and study groups,according to a random number table,with 50 patients in each *** control group received routine intervention,and the study group received acupoint massage combined with touch on the basis of the control ***[assessed using the Modified dental Anxiety Scale(MDAS)],pain severity,blood pressure,heart rate,and satisfaction were compared between the two *** Before intervention,the difference in MDAS score between the two groups was not significant(P>0.05),while after the intervention,the MDAS scores decreased in both groups compared with those before the intervention(Pdegree of pain in the intervention group was significantly lower than that in the control group(Plic and diastolic blood pressures or heart rate between the two groups(P>0.05).The systolic and d

关键词： Oral implant Acupoint massage Touch Anxiety degree of pain

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Protein tyrosine phosphatase non-receptor Ⅱ:A possible biomarker of poor prognosis and mediator of immune evasion in hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第9期16卷 3913-3931页

作者： Hui-Yuan li yi-Ming Jing Xue Shen Ming-Yue Tang hong-hong Shen Xin-Wei li Zi-Shu wang fang Su department of medical Oncology The First Affiliated Hospital of Bengbu Medical UniversityBengbu 233000Anhui ProvinceChina department of Neurology The First Affiliated Hospital of Bengbu Medical UniversityBengbu 233000Anhui ProvinceChina

BACKGROUND The incidence of primary liver cancer is increasing year by *** 2022 alone,more than 900000 people were diagnosed with liver cancer worldwide,with hepatocellular carcinoma(HCC)accounting for 75%-85%of *** is the most common primary liver *** has the highest incidence and mortality rate of HCC in the world,and it is one of the malignant tumors that seriously threaten the health of Chinese *** onset of liver cancer is occult,the early cases lack typical clinical symptoms,and most of the patients are already in the middle and late stage when ***,it is very important to find new markers for the early detection and diagnosis of liver cancer,improve the therapeutic effect,and improve the prognosis of *** tyrosine phosphatase non-receptor 2(PTPN2)has been shown to be associated with colorectal cancer,triple-negative breast cancer,non-small cell lung cancer,and prostate cancer,but its biological role and function in tumors remain to be further *** To combine the results of relevant data obtained from The Cancer Genome Atlas(TCGA)to provide the first in-depth analysis of the biological role of PTPN2 in *** The expression of PTPN2 in HCC was first analyzed based on the TCGA database,and the findings were then verified by immunohistochemical staining,quantitative real-time polymerase chain reaction(qRT-PCR),and *** value of PTPN2 in predicting the survival of patients with HCC was assessed by analyzing the relationship between PTPN2 expression in HCC tissues and clinicopathological ***,the potential of PTPN2 affecting immune escape of liver cancer was evaluated by tumor immune dysfunction and exclusion and immunohistochemical *** The results of immunohistochemical staining,qRT-PCR,and immunoblotting in combination with TCGA database analysis showed that PTPN2 was highly expressed and associated with a poor prognosis in HCC *** Encyclopedia of Ge

关键词： Protein tyrosine phosphatase non-receptor 2 Hepatocellular carcinoma Immune evasion Biomarker Immunotherapy Prognosis

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Adrenocorticotropic hormone combined with magnesium sulfate therapy for infantile epileptic spasms syndrome:a real-world study

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World Journal of Pediatrics 2024年第8期20卷 834-847页

作者： Wen He Qiu-hong wang Jiu-Wei li Yang-Yang wang Xiao-Mei Luo lin Wan Jing wang Xiu-Yu Shi Wei-Hua Zhang fang fang li-Ping Zou Senior department of Pediatrics the Seventh Medical Center of Chinese PLA General HospitalDepartment of Pediatricsthe First Medical Center of Chinese PLA General HospitalBeijing 100853China department of Neurology Beijing Children’s HospitalCapital Medical UniversityBeijingChina Center of Epilepsy Beijing Institute for Brain DisordersBeijing 100069China

Background Infantile epileptic spasms syndrome(IESS)is a serious disease in infants,and it usually evolves to other epilepsy types or syndromes,especially refractory or super-refractory focal *** adrenocorticotropic hormone(ACTH)is one of the first-line and effective treatment plans for IESS,it has serious side effects and is not sufficiently *** A retrospective study of the clinical outcomes of ACTH combined with magnesium sulfate(MgSO4)therapy for IESS in two hospital centers was *** major outcome of the single and combined treatment was evaluated by changes in seizure frequency and improvements in hypsarrhythmia electroencephalography(EEG).To reduce the confounding bias between the two groups,we used SPSS for the propensity score matching(PSM)*** We initially recruited 1205 IESS patients from two Chinese hospitals and treated them with ACTH combined with MgSO4 and ACTH *** 1005 patients were enrolled in the treatment(ACTH combined with MgSO4:744,ACTH:261),and both treatment plans had a more than 55%response ***,compared to patients treated with ACTH alone,those patients treated with ACTH combined with MgSO4 had better performance in terms of the seizure frequency and hypsarrhythmia *** PSM,the two groups also showed significant differences in responder rate[70.8%(95%confidence interval,CI)=66.7%–74.8%)vs.53.8%(95%CI=47.4%–60.2%),Pquency(Plinical *** with less than 3 months of lead time responded to the treatment much better than those with>3 months(Pdence of adverse reactions in the ACTH combined with MgSO4 group was much lower than that in the ACTH group(31.4%vs.63.1%,P<0.001).During the treatment,only

关键词： Adrenocorticotropic hormone Clinical trial Infantile epileptic spasms syndrome Magnesium sulfate Real-world study

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Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis

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Zoological Research 2024年第3期45卷 617-632页

作者： Jing-Hang Jiang yi-Fu wang Jie Zheng yi-Ming Lei Zhong-Yuan Chen yi Guo Ya-Jie Guo Bing-Qian Guo Yu-fang Lv hong-hong wang Juan-Juan Xie yi-Xuan liu Ting-Wei Jin Bi-Qi li Xiao-Shu Zhu Yong-Hua Jiang Zeng-Nan Mo Center for Genomic and Personalized Medicine Guangxi Collaborative Innovation Center for Genomic and Personalized MedicineGuangxi Key Laboratory for Genomic and Personalized MedicineGuangxi Medical UniversityNanningGuangxi 530021China department of Urology First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530021China Reproductive Medicine Center Jingmen People’s HospitalJingChu University of Technology Affiliated Central HospitalJingmenHubei 448000China School of Computer Science and Engineering Yulin Normal UniversityYulinGuangxi 537000China Collaborative Innovation Centre of Regenerative Medicine and medical BioResource development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanningGuangxi 530021China department of Pathology Second Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530007China department of Obstetrics and Gynecology Second Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530007China

The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in ***,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and *** compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and *** showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and *** analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal ***,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association ***,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal *** comprehensive results(publicly available at http://***:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

关键词： Tree shrew Adrenal gland dehydroepiandrosterone Genome-wide association studies Disease model

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Oxidation behavior of Ni-based superalloy GH4738 under tensile stress

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Rare Metals 2024年第8期43卷 3913-3920页

作者： Ji-Chong Hu Hai-liang Huang Chong-Chong Wu Xiao-Yu Sun Jie wang Yan-hong Yang Jing-long qu liang Jiang Jin-He Dou Yang Chen Institute for Advanced Studies in Precision Materials Yantai UniversityYantai 264005China department of Management and Engineering Linkoping University58183LinkopingSweden Shi-Changxu Innovation Center for Advanced Materials Institute of Metal ResearchChinese Academy of SciencesShenyang110016China Gaona Aero Material Co. LtdBeijing 100081China college of Artificial Intelligence and Big Data Shandong First Medical University and Shandong Academy of Medical SciencesJinan250117China

Revealing the oxidation behavior of superalloys is crucial for optimizing material properties and extending service *** study investigated the oxidation behavior of superalloy GH4738 under stress states at 850℃.High-throughput specimens were fabricated to withstand different stresses at the same *** oxidation s amples were analyzed using the mass gain method to obtain oxidation kinetic *** results show that the external stress below 200 MPa could improve the oxidation resistance of the *** tensile stress increasing,the oxide layer becomes thinner,denser and more complete,while internal oxidation *** tensile stress alters the structure of the external oxide layer from a two-layer to a threelayer *** Cr_(2)O_(3) oxide layer inhibits the outward diffusion of Ti,leading to Ti enrichment at the oxide-matrix interface and altering the oxidation mechanism of GH4738.

关键词： Ni-based Superalloy Oxidation behavior Tensile stress Oxide layer

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Fluorine-doped carbon quantum dots with deep-red emission for hypochlorite determination and cancer cell imaging

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Chinese Chemical Letters 2024年第6期35卷 433-438页

作者： Boran Cheng Lei Cao Chen li fang-yi Huo Qian-fang Meng Ganglin Tong Xuan Wu lin-lin Bu Lang Rao Shubin wang department of Oncology Shenzhen Key Laboratory of Gastrointestinal Cancer Translational ResearchCancer InstitutePeking University Shenzhen HospitalShenzhen-Peking University-Hong Kong University of Science and Technology Medical CenterShenzhen 518036China Institute of Biomedical Health Technology and Engineering Shenzhen Bay LaboratoryShenzhen 518132China The State Key Laboratory Breeding Base of Basic Science of Stomatology(Hubei-MOST)&Key Laboratory of Oral Biomedicine Ministry of Education School&Hospital of StomatologyWuhan UniversityWuhan 430079China

As a type of new carbon-based nanomaterials,carbon dots(CDs)possess exceptional optical properties,making them highly desirable for use in fluorescent ***,the CDs with deep-red(DR)or near-infrared(NIR)emission have rarely been *** this work,we prepared deep-red emissive fluorine-doped carbon quantum dots(F-CDs)by introducing a precursor simultaneously containing fluorine and *** synergistic effect of nitrogen doping and D-π-A pattern production contributed to the maximum emission of F-CDs at 636 nm with an absolute quantum yield of 36.00%±0.68%.Moreover,we designed an F-CDs-based fluorescence assay to determine the content of hypochlorite(ClO^(-)),with a limit of detection(LOD)as low as 15.4 nmol/L,indicating the high sensitivity of F-CDs to ClO^(-).In real samples,the F-CDs-based fluorescent sensor exhibited excellent sensitivity and selectivity in the detection of ClO^(-),with an error below 2%,suggesting their great potential in daily *** cancer cell imaging,the F-CDs not only demonstrated high sensitivity to ClO^(-)but also exhibited excellent mitochondria targeting,as evidenced by the high Pearson's correlation coefficient(PCC)of 0.93 in colocalization *** work presented here suggests the great potential of replacing commercial dyes with F-CDs for highly specific mitochondria labeling and cell imaging.

关键词： Carbon dots Near-infrared Cell imaging Mitochondria labeling Hypochlorite determination

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Efficacy and Safety of Sanjie Analgesic Capsule in Patients with Endometriosis-Associated Pain:A Multicenter,3:1 Randomized,Double-Blind,Placebo-Controlled Trial

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Chinese Journal of Integrative Medicine 2024年第9期30卷 780-787页

作者： LENG Jin-hua DUAN Hua GUAN Zheng ZHOU ying-fang qu hong XU Kai-hong ZHANG Shao-fen ZHANG Qin wang Xin liN Kai-qing LANG Jing-he department of Obstetrics and Gynecology Peking Union Medical College HospitalBeijing100730China department of Gynecology Beijing Obstetrics and Gynecology HospitalCapital Medical UniversityBeijing100006China department of Gynecology Chinese PLA General HospitalBeijing100039China department of Gynecology Peking University First HospitalBeijing100034China department of Gynecology Beijing Chao-yang HospitalBeijing100020China department of Gynecology Womens Hospital School of Medicine Zhejiang UniversityHangzhouZhejiang Province310006China department of Gynecology Obstetrics and Gynecology Hospital of Fudan UniversityShanghai200090China department of Gynecology Hangzhou Hospital of Traditional Chinese MedicineHangzhou310007China department of Gynecology Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang110032China

Objective:To assess the efficacy and safety of Sanjie Analgesic Capsule(SAC)in Chinese patients with endometriosis-associated ***:This was a multicenter,randomized,double-blind,placebo-controlled trial conducted at 15 centers between November 2013 and July 2017 in *** 323 patients with endometriosis were randomized at a 3:1 ratio to the SAC group(241 cases)and placebo group(82 cases)by stratified block *** in the SAC or placebo groups were given SAC or placebo 1.6 g 3 times per day,orally,respectively since the first day of menstruation for 3 consecutive menstrual *** primary endpoint was clinical response to dysmenorrhea evaluated using a 10-point Visual Analogue Scale at 3 and 6 *** secondary endpoint was the pain score evaluated by VAS(chronic pelvic pain,defecation pain,and dyspareunia)at 3 and 6 months,and the pain recurrence rate at 6 *** events(AEs)were recorded during the ***:A total of 241 women were included in the SAC group,and 82 were in the placebo *** these women,217(90.0%)and 71(86.6%)completed the intervention,*** 3 months,overall response rate(ORR)was significantly higher in women administered SAC(80.1%)compared with those who received a placebo(30.5%,P1).Six months after treatment,the ORR for dysmenorrhea was 62.7%in the SAC group and 31.7%in the placebo group(P1).Chronic pelvic pain and defecation pain were significantly improved by SAC compared with placebo(both Pdence rates of total AEs events in the SAC and placebo groups were 6.6%and 9.8%,respectively,and no significant difference was shown between the two groups(P=0.339).Conclusion:SAC is well-tolerated and may improve dysmenorrhea in women with endometriosis-associated pain.

关键词： endometriosis pain Sanjie Analgesic Capsule randomized controlled trial Chinese medicine

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Plexin domain-containing 1 may be a biomarker of poor prognosis in hepatocellular carcinoma patients,may mediate immune evasion

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2091-2112页

作者： Ming-Yue Tang Xue Shen Run-Sheng Yuan Hui-Yuan li Xin-Wei li yi-Ming Jing Yue Zhang hong-hong Shen Zi-Shu wang Lei Zhou Yun-Chuan Yang He-Xin Wen fang Su department of medical Oncology The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina Otolaryngology and Head and Neck Surgery The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina department of Neurology The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina department of Hepatobiliary Surgery The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina department of Gastrointestinal Surgery The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina

BACKGROUND For the first time,we investigated the oncological role of plexin domain-containing 1(PLXDC1),also known as tumor endothelial marker 7(TEM7),in hepatocellular carcinoma(HCC).AIM To investigate the oncological profile of PLXDC1 in *** Based on The Cancer Genome Atlas database,we analyzed the expression of PLXDC1 in *** immunohistochemistry,quantitative real-time polymerase chain reaction(qRT-PCR),and Western blotting,we validated our *** prognostic value of PLXDC1 in HCC was analyzed by assessing its correlation with clinicopathological features,such as patient survival,methylation level,tumor immune microenvironment features,and immune cell surface checkpoint ***,to assess the immune evasion potential of PLXDC1 in HCC,we used the tumor immune dysfunction and exclusion(TIde)website and immunohistochemical staining *** Based on immunohistochemistry,qRT-PCR,and Western blot assays,overexpression of PLXDC1 in HCC was associated with poor *** and multivariate Cox analyses indicated that PLXDC1 might be an independent prognostic *** HCC patients with high methylation levels,the prognosis was worse than in patients with low methylation *** enrichment analysis of HCC tissues indicated that genes upregulated in the high-PLXDC1 subgroup were enriched in mesenchymal and immune activation signaling,and TIde assessment showed that the risk of immune evasion was significantly higher in the high-PLXDC1 subgroup compared to the low-PLXDC1 *** high-risk group had a significantly lower immune evasion rate as well as a poor prognosis,and PLXDC1-related risk scores were also associated with a poor *** As a result of this study analyzing PLXDC1 from multiple biological perspectives,it was revealed that it is a biomarker of poor prognosis for HCC patients,and that it plays a role in determining immune evasion status.

关键词： Plexin domain-containing 1 Biomarker Immune evasion Prognosis Immunotherapy Hepatocellular carcinoma

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