CircPMS1 promotes proliferation of pulmonary artery smooth muscle cells,pulmonary microvascular endothelial cells,and pericytes under hypoxia

Background:Circular RNAs(circRNAs)have been recognized as significant regulators of pulmonary hypertension(PH);however,the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown.Here,we identified co-differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells(PASMCs),pulmonary microvascular endothelial cells(PMECs),and pericytes(PCs)under hypoxia.Methods:Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types.Bioinformatic analysis was used to predict their putative biological function.Quantitative real-time polymerase chain reaction,Cell Counting Kit-8,and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1(circPMS1)as well as its potential sponge mechanism in PASMCs,PMECs,and PCs.Results:PASMCs,PMECs,and PCs exhibited 16,99,and 31 differentially expressed circRNAs under hypoxia,respectively.CircPMS1 was upregulated in PASMCs,PMECs,and PCs under hypoxia and enhanced the proliferation of vascular cells.CircPMS1may upregulate DEP domain containing 1(DEPDC1)and RNA polymerase II subunit D expression by targeting microRNA-432-5p(miR-432-5p)in PASMCs,upregulate MAX interactor 1(MXI1)expression by targeting miR-433-3p in PMECs,and upregulate zinc finger AN1-type containing 5(ZFAND5)expression by targeting miR-3613-5p in PCs.Conclusions:Our results suggest that circPMS1 promotes cell proliferation through the miR-432-5p/DEPDC1 or miR-432-5p/POL2D axis in PASMCs,through the miR-433-3p/MXI1 axis in PMECs,and through the miR-3613-5p/ZFAND5 axis in PCs,which provides putative targets for the early diagnosis and treatment of PH.

Early expressions of hypoxia-inducible factor 1alpha and vascular endothelial growth factor increase the neuronal plasticity of activated endogenous neural stem cells after focal cerebral ischemia

Endogenous neural stem cells become ＂activated＂ after neuronal injury, but the activation sequence and fate of endogenous neural stem cells in focal cerebral ischemia model are little known. We evaluated the relationships between neural stem cells and hypoxia-inducible factor-1α and vascular endothelial growth factor expression in a photothromobotic rat stroke model using immunohistochemistry and western blot analysis. We also evaluated the chronological changes of neural stem cells by 5-bromo-2′-deoxyuridine（BrdU） incorporation. Hypoxia-inducible factor-1α expression was initially increased from 1 hour after ischemic injury, followed by vascular endothelial growth factor expression. Hypoxia-inducible factor-1α immunoreactivity was detected in the ipsilateral cortical neurons of the infarct core and peri-infarct area. Vascular endothelial growth factor immunoreactivity was detected in bilateral cortex, but ipsilateral cortex staining intensity and numbers were greater than the contralateral cortex. Vascular endothelial growth factor immunoreactive cells were easily found along the peri-infarct area 12 hours after focal cerebral ischemia. The expression of nestin increased throughout the microvasculature in the ischemic core and the peri-infarct area in all experimental rats after 24 hours of ischemic injury. Nestin immunoreactivity increased in the subventricular zone during 12 hours to 3 days, and prominently increased in the ipsilateral cortex between 3–7 days. Nestin-labeled cells showed dual differentiation with microvessels near the infarct core and reactive astrocytes in the peri-infarct area. BrdU-labeled cells were increased gradually from day 1 in the ipsilateral subventricular zone and cortex, and numerous BrdU-labeled cells were observed in the peri-infarct area and non-lesioned cortex at 3 days. BrdU-labeled cells rather than neurons, were mainly co-labeled with nestin and GFAP. Early expressions of hypoxia-inducible factor-1α and vascular endothelial growth factor after ischemia made up the microenvironment to increase the neuronal plasticity of activated endogenous neural stem cells. Moreover, neural precursor cells after large-scale cortical injury could be recruited from the cortex nearby infarct core and subventricular zone.

Small interfering RNA targeting PGC-1α inhibits VEGF expression and tube formation in human retinal vascular endothelial cells

AIMTo determine whether small interfering RNA (siRNA) of PGC-1α could inhibit vascular endothelial growth factor (VEGF) expression and tube formation in human retinal vascular endothelial cells (hRVECs).METHODShRVECs transfected with peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) siRNA were incubated for 24h and then placed into a normoxic (20%, O2) or hypoxic (1%, O2) environment for another 16h. PGC-1α mRNA and protein levels were detected by real-time PCR and Western blot. VEGF mRNA and protein levels were detected by real-time PCR and ELISA. Cell proliferation was evaluated by BrdU incorporation assay. Forty-eight hours after siRNA transfection, hRVECs were planted into Matrigel-coated plates and cultured under normoxic (20%, O2) or hypoxic (1%, O2) conditions for another 48h. The tube formation of hRVECs was observed under an optical microscope and quantified by counting the number of branch points and calculating the total tube length.RESULTSPGC-1α mRNA and protein levels were significantly reduced by PGC-1α siRNA, and VEGF mRNA and protein levels also decreased significantly. The percentage of BrdU-labeled cells in siPGC-1α groups were significantly decreased compared with control siRNA groups under normoxia and hypoxia in cell proliferation assay. In the tube formation assay, PGC-1α siRNA treated cells formed significantly fewer tubes.CONCLUSIONBlocking PGC-1α expression can inhibit VEGF expression in hRVECs and inhibit their ability to form tubes under both normoxic and hypoxic conditions.

Vascular endothelial growth factor A, secreted in response to transforming growth factor-β1 under hypoxic conditions, induces autocrine effects on migration of prostate cancer cells

Hypoxia and transforming growth factor-β1 （TGF-β1） increase vascular endothelial growth factor A （VEGFA） expression in a number of malignancies. This effect of hypoxia and TGF-β1 might be responsible for tumor progression and metastasis of advanced prostate cancer. In the present study, TGF-β1 was shown to induce VEGFA165 secretion from both normal cell lines （HPV7 and RWPE1） and prostate cancer cell lines （DU 145 and PC3）. Conversely, hypoxia-stimulated VEGFA165 secretion was observed only in prostate cancer cell lines. Hypoxia induced TGF-β1 expression in PC3 prostate cancer cells, and the TGF-β1 type I receptor （ALK5） kinase inhibitor partially blocked hypoxia-mediated VEGFA16s secretion. This effect of hypoxia provides a novel mechanism to increase VEGFA expression in prostate cancer cells. Although autocrine signaling of VEGFA has been implicated in prostate cancer progression and metastasis, the associated mechanism is poorly characterized. VEGFA activity is mediated via VEGF receptor （VEGFR） 1 （Fit-l） and 2 （FIk-I/KDR）. Whereas VEGFR-1 mRNA was detected in normal prostate epithelial cells, VEGFR-2 mRNA and VEGFR protein were expressed only in PC3 cells. VEGFA165 treatment induced phosphorylation of extracellular signal-regulated kinase 1/2 （ERKI/2） in PC3 cells but not in HPV7 cells, suggesting that the autocrine function of VEGFA may be uniquely associated with prostate cancer. Activation of VEGFR-2 by VEGFA165 was shown to enhance migration of PC3 cells. A similar effect was also observed with endogenous VEGFA induced by TGF-β1 and hypoxia. These findings illustrate that an autocrine loop of VEGFA via VEGFR-2 is critical for the tumorigenic effects of TGF-β1 and hypoxia on metastatic prostate cancers.

靶向成纤维细胞生长因子受体1信号改善类风湿关节炎的骨破坏

背景:尽管科研人员已注意到成纤维细胞生长因子受体1在类风湿关节炎骨破坏中展现出巨大潜力,但尚未有学者对成纤维细胞生长因子受体1在类风湿关节炎骨破坏中的研究进展作全面综述。目的:通过查阅国内外相关文献,综合分析成纤维细胞生长因子受体1在类风湿关节炎骨破坏中的机制。方法:以“成纤维细胞生长因子受体1,类风湿关节炎,骨破坏,骨细胞,成骨细胞,破骨细胞,软骨细胞,巨噬细胞,滑膜成纤维细胞,T细胞,血管内皮细胞”为检索词检索中国知网数据库,以“fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,osteocytes,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,endothelial cells”为检索词检索PubMed数据库,检索时间范围重点为1992年4月至2024年1月。通过阅读文献题目、摘要及全文,根据纳入与排除标准进行筛选,最后纳入82篇文献进行综述。结果与结论:成纤维细胞生长因子受体1广泛表达于骨组织相关细胞,包括骨细胞、成骨细胞、破骨细胞等,可以通过调控这些细胞的功能来影响骨重塑过程和维持骨稳态,促进类风湿关节炎骨破坏的发生和发展。成纤维细胞生长因子受体1还可以在滑膜成纤维细胞和巨噬细胞中参与炎症反应,在内皮细胞中调控滑膜血管生成,从多个方面促进骨破坏。成纤维细胞生长因子受体1可能是类风湿关节炎骨破坏的一个重要参与因素,为进一步研究类风湿关节炎治疗靶点提供依据。

Knockdown of fibrillin-1 suppresses retina-blood barrier dysfunction by inhibiting vascular endothelial apoptosis under diabetic conditions

AIM:To investigate the effects of fibrillin-1(FBN1)deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic conditions.METHODS:Streptozotocin(STZ)-induced diabetic mice were used to simulate the diabetic conditions of diabetic retinopathy(DR)patients,and FBN1 expression was detected in retinas from STZ-diabetic mice and controls.In the Gene Expression Omnibus(GEO)database,the GSE60436 dataset was selected to analyze FBN1 expressions in fibrovascular membranes from DR patients.Using lentivirus to knock down FBN1 levels,vascular leakage and endothelial barrier integrity were detected by Evans blue vascular permeability assay,fluorescein fundus angiography(FFA)and immunofluorescence labeled with tight junction marker in vivo.High glucose-induced monkey retinal vascular endothelial cells(RF/6A)were used to investigate effects of FBN1 on the cells in vitro.The vascular endothelial barrier integrity and apoptosis were detected by trans-endothelial electrical resistance(TEER)assay and flow cytometry,respectively.RESULTS:FBN1 mRNA expression was increased in retinas of STZ-induced diabetic mice and fibrovascular membranes of DR patients(GSE60436 datasets)using RNA-seq approach.Besides,knocking down of FBN1 by lentivirus intravitreal injection significantly inhibited the vascular leakage compared to STZ-DR group by Evans blue vascular permeability assay and FFA detection.Expressions of tight junction markers in STZ-DR mouse retinas were lower than those in the control group,and knocking down of FBN1 increased the tight junction levels.In vitro,30 mmol/L glucose could significantly inhibit viability of RF/6A cells,and FBN1 mRNA expression was increased under 30 mmol/L glucose stimulation.Down-regulation of FBN1 reduced high glucose(HG)-stimulated retinal microvascular endothelial cell permeability,increased TEER,and inhibited RF/6A cell apoptosis in vitro.CONCLUSION:The expression level of FBN1 increases in retinas and vascular endothelial cells under diabetic conditions.Down-regulation of FBN1 protects the retina of early diabetic rats from retina-blood barrier damage,reduce vascular leakage,cell apoptosis,and maintain vascular endothelial cell barrier function.

肿瘤组织微小RNA-542-3p、血管细胞黏附分子-1表达特征与脑胶质瘤术后复发的关系及预测价值

目的:探讨肿瘤组织中微小RNA-542-3p(miR-542-3p)、血管细胞黏附分子-1(VCAM-1)表达与脑胶质瘤手术后复发的关系及其预测价值。方法:选取实施手术治疗的脑胶质瘤患者91例进行临床研究,其中43例患者于术后1年出现术后复发(复发组)、48例患者手术后1年检查未出现复发病灶(非复发组),对比两组第一次手术后病灶组织标本中的miR-542-3p、VCAM-1蛋白表达差异,并分析miR-542-3p、VCAM-1蛋白表达与胶质瘤术后复发的关系及其预测复发的价值。结果:复发组患者脑胶质瘤组织中miR-542-3p表达水平低于非复发组,复发组患者脑胶质瘤组织中VCAM-1蛋白阳性表达率高于非复发组,差异具有统计学意义(均P<0.05);复发组患者脑胶质瘤组织病理学分级≥Ⅲ级患者占比、低分化患者占比、非全切手术方式患者占比、肿瘤浸润率均高于非复发组,复发组患者术后放化疗患者占比低于非复发组,差异具有统计学意义(均P<0.05)。miR-542-3p表达降低、VCAM-1蛋白阳性表达、手术范围非全切是脑胶质瘤手术后复发的独立危险因素(均P<0.05);miR-542-3p表达、VCAM-1蛋白预测脑胶质瘤手术后复发的曲线下面积AUC值分别为0.784(95%CI:0.690~0.877)、0.725(95%CI:0.621~0.829)。结论:脑胶质瘤组织中miR-542-3p表达、VCAM-1蛋白表达与肿瘤手术后复发有密切关系,用于临床预测有一定的参考价值。

TIR/BB-loop mimetic AS-1 protects vascular endothelial cells from injury induced by hypoxia/reoxygenation

Morphological and functional abnormalities of vascular endothelial cells(VECs) are risk factors of ischemiareperfusion in skin flaps.Signaling pathway mediated by interleukin-1 receptor(IL-1 R) is essential to hypoxia/reoxygenation(H/R) injury of VECs.While the TIR/BB-loop mimetic(AS-1) disrupts the interaction between IL-1 R and myeloid differentiation primary-response protein 88(MyD88),its role in the VECs dysfunction under H/R is unclear.In this study,we first showed that there was an infiltration of inflammatory cells and the apoptosis of VECs by using a skin flap section from patients who received flap transplantation.We then showed that the H/R treatment induced apoptosis and loss of cell migration of endothelial cell line H926 were attenuated by AS-1.Furthermore,our data suggested that AS-1 inhibits the interaction between IL-1 R and MyD88,and subsequent phosphorylation of IκB and p38 pathway,as well as the nuclear localization of NF-κB subunit p65/p50.Thus,this study indicated that the protective role of AS-1 in H/R induced cellular injury may be due to the AS-1 mediated down-regulation of IL-1 R signaling pathway.

血管介入栓塞术治疗动脉瘤性蛛网膜下腔出血疗效及对患者血清高迁移率族蛋白B1、血清可溶性细胞间黏附因子-1、可溶性血管细胞黏附因子-1的影响

目的:探讨血管介入栓塞术治疗动脉瘤性蛛网膜下腔出血(aSAH)的疗效及对血清高迁移率族蛋白B1(HMGB1)、血清可溶性细胞间黏附因子-1(sICAM-1)、可溶性血管细胞黏附因子-1(sVCAM-1)的影响。方法:选择92例aSAH患者为研究目标,根据手术方法不同分为对照组(颅内动脉瘤夹闭术治疗)46例,观察组(血管介入栓塞术治疗)46例,比较两组手术前后免疫功能及sICAM-1、sVCAM-1、HMGB1水平变化,记录手术时间、并发症发生率、住院时间,并评估预后情况。结果:观察组手术时间、住院时间分别为(92.03±14.97)min、(18.73±4.41)d均短于对照组的手术时间(147.92±34.21)min,术后住院时间(23.35±4.15)d(均P<0.05);术后观察组免疫功能高于对照组(P<0.05);观察组术后HMGB1、sICAM-1、sVCAM-1水平低于对照组(均P<0.05);对照组不良反应总发生率高于观察组(P<0.05);对照组知期预后良好率低于观察组(P<0.05)。结论:血管介入栓塞术治疗aSAH手术耗时短、脑血管痉挛发生率低、免疫状态影响小,并可明降低血清HMGB1、sICAM-1、sVCAM-1水平。

Activation of α7 nicotinic acetylcholine receptor protects against oxidant stress damage through reducing vascular peroxidase-1 in a JNK signaling-dependent manner in endothelial cells

Aim Alpha7 nicotinic acetylcholine receptor （α7nAChR）, a subtype of nAChR regulating neurotrans- mission in central nervous system, is an essential regulator of cholinergic antiinflammatory pathway in periphery. The present study was to determine the effects of activation of α7nAChR on oxidant stress-induced injury in endo- thelial cells. Methods Cultured human umbilical vein endothelial cells were treated with H202 （400 μmol · L^-1） or H202plus PNU-282987 （ 10 μmol · L^-1 ）. Cell viability and membrane integrity were measured. AnnexinV ＋ PI assay, immunoblotting of bcl-2, bax and cleaved caspase-3, and immunofluorescence of apoptosis inducing factor （AIF） were performed to evaluate apoptosis. Protein expression of vascular peroxidase-1 （ VPO-1 ） and phosphor- JNK were measured by immunoblotting. Results Activation of α7nAChR by a selective agonist PNU-282987 pre-vented H202-indced decrease of cell viability and increase of lactate dehydrogenase release. Activation of α7nAChR markedly reduced cell apoptosis and intracellular oxidative stress level. Moreover, activation of α7nAChR reduced H2 02 -induced VPO-1 protein upregulation and JNK1/2 phosphorylation. The inhibitory effect of α7nAChR activa- tion on VPO-1 was blocked by JNK inhibitor SP600125. In addition, pretreatment of α7nAChR antagonist methyl- lycaconitine blocked the cytoprotective effect of PNU-282987. Conclusion These results provide the first evidence that activation of α7nAChR protects against oxidant stress-induced damage by suppressing VPO-1 in a JNK signa- ling pathway-dependent manner in endothelial cells.

Increased serum TREM-1 level is associated with in-stent restenosis,and activation of TREM-1 promotes inflammation,proliferation and migration in vascular smooth muscle cells

Background and Objective In-stent restenosis(ISR)remains a major limitation of percutaneous coronary intervention despite improvements in stent design and pharmacological agents,whereas the mechanism of ISR has not been fully clarified.In the present study,we sought to investigate the potential association of serum soluble TREM-1(sTREM-1)levels with the incidence of ISR.The role of TREM-1 was evaluated in cultured vascular smooth muscle cells(VSMCs).

Medicated Serum of Qishen Yiqi Pill Affect Vascular Smooth Muscle Cell Proliferation,Cell Cycle,Cyclin D1 and CDK4 Mechanism Research

Observation of stilbene dropping pill and yiqi drug-containing serum influence mechanism of vascular smooth muscle proliferation， cell cycle and Cyclin D1 and CDK4Choose male SD rats were randomly divided into 2 groups， lavage qishen yiqi pill and the gastric saline group，extract the drug-containing serum and normal serum；To set the two groups of serum respectively different concentrations，concentration in different time by CCK8 detection effects on vascular smooth muscle cell proliferation， select best concentration and action time.Flow cytometry instrument and high-throughput screening detect serum medicated effect on vascular smooth muscle cell cycle；Western blot detect the drug-containing serum of cell cycle protein Cyclin D1 and CDK4 expression.Result is 5%， 10% medicated serum inhibits cell proliferation significantly higher than the normal serum concentrations of same within 24 h， 48 h.G1 phase cells 5% medicated serum group was obviously higher than that of 5% in normal group (P<005)， serum and cell proliferation index significantly less than 5% normal serum group (P<005)，At the same time， Cyclin D1 and CDK4 expression significantly less than 5% normal serum group (P<005).Conclusion serum of qishen yiqi pill can inhibit vascular smooth muscle cell proliferation， may be through inhibiting cell cycle protein Cyclin D1 and CDK4 expression， block the cell cycle G1 process is closely related to the role.

Effects of IGF-1 and oxLDL on expression of phosphatase PHLPP1 in vascular smooth muscular cells

Objective To investigate the effects of insulin-like growth factor-1 （IGF-1） and oxidized low density lipoprotein （oxLDL） on expression ofphosphatase PHLPP 1 in vascular smooth muscle cells （VSMCs）. Methods Rabbit aortic VSMCs were cultured. VSMCs proliferation ability was determined by measuring cell number and mitochondrial dehydrogenase （MD） activity with MTT assay. Western blot was used to detect the protein expression ofphosphatase PHLPP1. Results IGF-1 （100ug/L） increased cell number and MD activity to 3.02 and 3.59 times of that in control group, oxLDL（501xg/ml） elevated the above two parameters to 2.03 and 2.91 times respectively. Western blot showed that IGF-1 and oxLDL inhibited the expression of PHLPPI to 39.27% and 40.26% of the control group （P〈0.01 ）. Conclusion IGF- 1 and oxLDL may enhance the proliferation of VSMCs by decreasing the expression ofphosphatase PHLPP 1.

A bioinformatics-based study of the mechanism of JQ-1 on BET protein and atherosclerosis induced by vascular smooth muscle cell proliferation

Background:Based on previous theoretical studies,JQ-1 as a common inhibitor of bromodomain and extraterminal(BET)proteins was used to treat a variety of diseases.Therefore,we aimed to explore the mechanism of action of JQ-1 on BET proteins based on bioinformatics and build the novel hypothesis of JQ-1 in treating atherosclerosis(AS)caused by proliferation of vascular smooth muscle cells(VSMCs).Methods:We selected the chip GSE138323 which was searched with the key words“Vascular smooth muscle cell proliferation”in Gene Expression Omnibus(GEO)database,and differential gene analysis was performed between the GRO and JQ-1 groups.Then the top twenty significantly up-regulated genes and the top twenty significantly down-regulated genes were selected for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Thirdly,structured the PPI network of forty differential genes,and the core genes were screened by using the MCC algorithm which in“Cytohubba”plugin in the Cytoscapev3.9.1 software.After that,single gene Gene Set Enrichment Analysis(GSEA)enrichment analysis was performed on the selected core genes in R language.Finally molecular docking validation was performed.Results:Five core genes was selected:H3C2,H3C4,H3C7,H3C10 and AREG.The GO enrichment analysis results showed that there were twenty-five entries in biological process,eight entries in cellular components(CC),and twenty-five entries in molecular function.The KEGG enrichment analysis results showed that there were seven pathways,mainly including systemic lupus erythematosus and external neutrophil trap formation.The GSEA results showed that the five genes were mainly through the regulation of cytochrome P450 metabolism,PPAR signaling pathway and other pathways.The molecular docking results showed that JQ-1 had binding activity with these five genes.Conclusions:JQ-1 may regulate the expression of the genes that H3C2,H3C4,H3C7,H3C10 and AREG,to mainly regulate the genes in cytochrome P450 metabolism,PPAR singling pathway and other pathways,to make some influence in the proliferation of VSMCs,and improved atherosclerotic symptoms due to vascular smooth muscle proliferation,thus treating cardiovascular disease.

血栓心脉宁片通过调控TGF-β_(1)和Runx2表达抑制血管平滑肌细胞钙化的研究

目的探讨血栓心脉宁片是否可通过调控转化生长因子β_(1)(TGF-β_(1))和Runt相关转录因子2(Runx2)表达抑制血管平滑肌细胞的钙化。方法取对数生长期大鼠血管平滑肌细胞,实验分为5组:阴性组细胞加入DMEM培养液培养;钙化组加入β-磷酸甘油(β-GP)作用24 h诱导血管平滑肌细胞钙化;血栓心脉宁低、中、高剂量组先分别加入125 mg/L、250 mg/L、500 mg/L的血栓心脉宁片培养24 h后再给予β-GP作用24 h。采用CCK-8法检测各组细胞活力,酶标仪检测各组细胞中钙含量、碱性磷酸酶(ALP)活性及TGF-β_(1)含量,Western blot法检测细胞中Runx2蛋白表达情况。结果与阴性组比较,钙化组细胞活力明显下降(P<0.05),细胞中钙含量、ALP活性、TGF-β_(1)含量及Runx2蛋白相对表达量均明显升高(P均<0.05);与钙化组比较,血栓心脉宁各组细胞活力均明显提高(P均<0.05),细胞中钙含量、ALP活性、TGF-β_(1)含量及Runx2蛋白相对表达量均明显降低(P均<0.05),且各指标均呈浓度依赖性变化。结论血栓心脉宁片可能通过调控TGF-β_(1)和Runx2的表达,抑制大鼠血管平滑肌细胞的钙化。

儿童慢性粒细胞白血病慢性期红细胞参数及血清bFGF、TGF-β1、VEGF表达变化分析

目的探究儿童慢性粒细胞白血病(CML)慢性期红细胞参数及血清碱性成纤维细胞生长因子(bFGF)、转化生长因子β1(TGF-β1)及血管内皮生长因子(VEGF)表达变化。方法前瞻性选取2020年1月至2023年1月在首都医科大学附属北京儿童医院进行治疗的54例CML慢性期患儿为研究组,另随机抽取46名同期在本院进行体检的健康儿童为健康对照组。研究组给予酪氨酸激酶抑制剂治疗。比较两组间红细胞参数及血清bFGF、TGF-β1、VEGF表达变化,并比较研究组治疗前后红细胞参数及血清bFGF、TGF-β1、VEGF表达水平。结果研究组的RBC、血红蛋白、红细胞压积(HCT)及平均红细胞血红蛋白浓度(MCHC)水平分别为(3.45±0.04)×10^(12)/L、(102.33±1.15)g/L、(32.03±0.61)%、322.15±2.58,均显著低于对照组[(4.98±0.03)×10^(12)/L、(149.78±1.88)g/L、(44.33±0.31)%、334.12±0.77],平均红细胞体积(MCV)、平均红细胞血红蛋白含量(MCH)及红细胞体积分布宽度(RDW)水平分别为(91.44±0.77)fL、(33.15±2.55)pg、(17.55±0.12)%,均显著高于对照组[(89.88±0.34)fL、(30.24±0.16)pg、(12.66±0.11)%],差异均有统计学意义(P<0.05)。研究组的血清bFGF、VEGF水平分别为(30.66±9.66)、(128.68±30.58)pg/mL,均显著高于对照组[(5.26±1.54)、(70.66±11.26)pg/mL],TGF-β1水平为(38.22±8.06)μg/L,显著低于对照组[(78.66±8.13)μg/L],差异均有统计学意义(P<0.05)。治疗后,研究组患儿的RBC、血红蛋白、HCT、MCV及MCH水平均较治疗前显著降低,MCHC及RDW水平均较治疗前显著升高,差异均有统计学意义(P<0.05)。研究组治疗后的血清bFGF、VEGF水平均较治疗前显著降低,TGF-β1水平较治疗前显著升高,差异均有统计学意义(P<0.05)。结论在儿童CML慢性期患儿中可见血细胞参数明显异常,血清bFGF、VEGF水平显著升高,TGF-β1水平显著降低。酪氨酸激酶抑制剂治疗CML慢性期能有效改善患儿红细胞形态及功能,抑制肿瘤细胞生长,临床疗效显著,值得临床推广使用。

血管内皮生长因子、程序性死亡受体-1联合胃功能三项对早期胃癌的诊断及预后评估价值

目的:探讨血管内皮生长因子(VEGF)、程序性死亡受体-1(PD-1)联合胃功能三项对早期胃癌(EGC)的诊断及预后评估价值。方法:选取EGC患者167例为EGC组,对术中的胃癌及癌旁组织进行收集,免疫组织化学染色后比较VEGF、PD-1阳性表达情况。另选取本院同期体检健康者74例为对照组,比较EGC组与对照组胃功能三项[胃蛋白原Ⅰ(PGⅠ)、胃蛋白原Ⅱ(PGⅡ)和胃泌素17(G17)]水平。所有患者均进行为期3年随访,根据是否病死分为预后良好组和预后不良组,比较两组临床病理资料。Logistic回归分析EGC患者预后不良的影响因素,Pearson法分析各指标的相关性,受试者工作特征(ROC)曲线分析VEGF、PD-1联合胃功能三项检测在EGC患者诊断及预后评估中的应用价值。结果:EGC组患者癌旁组织VEGF、PD-1阳性表达率低于胃癌组织(均P<0.05)。与对照组比较,EGC组PGⅠ水平降低,PGⅡ、G17水平升高(均P<0.05)。根据随访结果,预后不良组59例,预后良好组108例。预后不良组患者VEGF和PD-1阳性表达率以及PGⅡ、G17水平高于预后良好组,中高分化占比和PGⅠ水平低于预后良好组(均P<0.05)。低PGⅠ水平、高VEGF和PD-1阳性表达率、低分化、高PGⅡ和G17水平是EGC患者预后不良的危险因素(均P<0.05)。VEGF、PD-1、PGⅡ、G17水平与分化程度呈负相关,PGⅠ水平与分化程度呈正相关(均P<0.05)。VEGF、PD-1联合胃功能三项检测对EGC患者均有一定的诊断和预后评估价值,联合检测的价值更高(均P<0.05)。结论:VEGF、PD-1在胃癌组织中高表达,两者联合胃功能三项对EGC的诊断和预后评估均有较高价值。

冠心病患者血清VCAM-1、miR-145、Gal-3、SFRP5水平变化

目的探讨冠心病患者血清血管细胞黏附分子-1(VCAM-1)、miR-145、半乳糖凝集素-3(Gal-3)、分泌型卷曲蛋白5(SFRP5)水平变化及意义。方法选取冠心病患者80例为冠心病组,另收集健康志愿者40名为健康对照组。采集清晨空腹肘静脉血,酶联免疫吸附法测定血清VCAM-1、Gal-3、SFRP5浓度;RT-PCR检测血清miR-145表达水平。根据冠脉造影检查诊断的病变支数分为单支病变、双支病变、多支病变。收集两组受试者人口学特征及冠心病患者实验室指标;进行1 a随访,记录不良预后发生情况(病情加重再入院、死亡)。结果冠心病组患者血清VCAM-1、Gal-3水平明显高于健康对照组,miR-145、SFRP5水平明显低于健康对照组(均P<0.01)。急性心肌梗死组患者血清VCAM-1、Gal-3水平明显高于不稳定型心绞痛组、稳定型心绞痛组患者,血清miR-145、SFRP5水平明显低于不稳定型心绞痛组、稳定型心绞痛组患者(均P<0.05)。多支病变患者血清VCAM-1、Gal-3水平明显高于双支病变和单支病变患者,血清miR-145、SFRP5水平明显低于双支病变和单支病变患者(均P<0.05)。预后不良组患者血清VCAM-1、Gal-3水平明显高于预后良好组患者,miR-145、SFRP5水平明显低于预后良好组患者(均P<0.01)。VCAM-1、miR-145、Gal-3、SFRP5水平是冠心病患者预后的独立影响因素;ROC曲线分析显示,血清VCAM-1、miR-145、Gal-3、SFRP5水平联合检测对冠心病患者预后具有较高的预测价值(AUC=0.928)。结论冠心病患者血清VCAM-1、Gal-3水平高表达,miR-145、SFRP5水平低表达,且与冠心病分类、冠脉病变支数密切相关,联合检测对预后具有较高的预测价值。

血清VCAM-1、PECAM-1水平与MMSE评分联合检测对老年全髋关节置换术患者术后谵妄的预测价值

目的探讨术前血清血管细胞黏附分子-1(VCAM-1)、血小板内皮细胞黏附分子-1(PECAM-1)水平与简易精神状态量表(MMSE)评分联合检测对老年全髋关节置换术(THA)患者术后谵妄(POD)的预测价值。方法选择住院并行手术治疗的髋部骨折老年患者200例作为研究对象,并根据术后3 d内是否发生POD分为POD组(44例)和非POD组(156例)。收集2组患者的临床资料,术前采用MMSE评估患者的认知状况,并检测术前、术后第1天和第3天血清VCAM-1、PECAM-1水平。对比2组患者上述指标的差异,并分析术前血清VCAM-1、PECAM-1水平与MMSE评分的相关性。应用多因素Logistic回归分析老年THA患者发生POD的影响因素。构建受试者工作特征(ROC)曲线评估术前血清VCAM-1水平、PECAM-1水平、MMSE评分单独及联合检测对老年THA患者并发POD的预测价值。结果POD组年龄、医院焦虑抑郁量表评分、术中低血压发生率、术后住院时间明显高于或长于非POD组,MMSE评分低于非POD组(P<0.05)。POD组术前、术后第1天和术后第3天血清VCAM-1、PECAM-1水平升高,且高于非POD组(P<0.05)。老年THA患者术前血清VCAM-1、PECAM-1水平分别与MMSE评分呈负相关(r分别为-0.390、-0.501,均P<0.01)。术前血清VCAM-1和PECAM-1水平升高以及术后住院时间延长为老年THA患者发生POD的独立危险因素,MMSE评分升高为独立保护因素(P<0.05)。术前血清VCAM-1(AUC=0.793,95%CI:0.730~0.847)、PECAM-1(AUC=0.799,95%CI:0.736~0.852)及MMSE评分(AUC=0.805,95%CI:0.744~0.858)对THA患者发生POD均有较高的预测价值,三项指标联合预测的效能更高。结论血清VCAM-1、PECAM-1水平升高与老年THA患者认知功能受损有关,且均为老年THA患者发生POD的独立预测因子,术前检测以上指标可能对POD的早期防治具有重要价值。