Placenta-derived mesenchymal stem cells attenuate secondary brain injury after controlled cortical impact in rats by inhibiting matrix metalloproteinases

Background:As a form of biological therapy,placenta-derived mesenchymal stem cells(PDMSCs)exhibit considerable promise in addressing the complex pathological processes of traumaticbrain injury(TBI)due to their multi-target and multi-pathway mode of action.Material&Methods:This study investigates the protective mechanisms and benefits of PDMSCs in mitigating the effects of controlled cortical impact(CCI)in rats and glutamate-induced oxidative stress injury in HT22 cells in vitro.Our primary objective is to provide evidence supporting the clinical application of PDMSCs.Results:In the in vivo arm of our investigation,we observed a swift elevation of matrix metalloproteinase-9(MMP-9)in the proximal cortex of injured brain tissues after CCI.PDMSCs,distinguished by their heightened expression of metalloproteinase tissue inhibitors-1 and-2(TIMP-1 and TIMP-2):were intravenously administered via the caudal vein.This intervention yielded significant reductions in the permeability of the blood-brain barrier(BBB):the extent of brain edema,the levels of inflammatory cytokines IL-1βand TNF-αin damaged brain tissue,and the activation status of microglia in CCI-afflicted rats.In the realm of in vitro experiments,PDMSC-conditioned media demonstrated substantial reductions in mortality rates and cleaved caspase-3 levels in glutamate-induced HT22 cells compared with conventional media.Notably,this advantage was negated upon the introduction of neutralizing antibodies targeting TIMP-1 and TIMP-2.Conclusion:Collectively,our findings underscore the potential of PDMSCs in alleviating oxidative stress injury and secondary brain injury in the pathological process of TBI.

Association between Gene Polymorphisms and SNP-SNP Interactions of the Matrix Metalloproteinase 2 Signaling Pathway and the Risk of Vascular Senescence

Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.

Diagnostic value of matrix metalloproteinases 2, 7 and 9 in urine for early detection of colorectal cancer

BACKGROUND A noninvasive biomarker with high diagnostic performance is urgently needed for the early diagnosis of colorectal cancer(CRC).AIM To evaluate the diagnostic value of matrix metalloproteinases(MMPs)2,7 and 9 in urine for CRC.METHODS Of 59 healthy controls,47 patients with colon polyps and 82 patients with CRC were included in this study.Carcinoembryonic antigen(CEA)in serum and MMP2,MMP7,and MMP9 in urine were detected.The combined diagnostic model of the indicators was established by binary logistic regression.The receiver operating characteristic curve(ROC)of the subjects was used to evaluate the independent and combined diagnostic value of the indicators.RESULTS The MMP2,MMP7,MMP9,and CEA levels in the CRC group differed significantly from levels in the healthy controls(P<0.05).The levels of MMP7,MMP9,and CEA also differed significantly between the CRC group and the colon polyps group(P<0.05).The area under the curve(AUC)distinguishing between the healthy control and the CRC patients using the joint model with CEA,MMP2,MMP7 and MMP9 was 0.977,and the sensitivity and specificity were 95.10%and 91.50%,respectively.For early-stage CRC,the AUC was 0.975,and the sensitivity and specificity were 94.30%and 98.30%,respectively.For advanced stage CRC,the AUC was 0.979,and the sensitivity and specificity were 95.70%and 91.50%,respectively.Using CEA,MMP7 and MMP9 to jointly established a model distinguishing the colorectal polyp group from the CRC group,the AUC was 0.849,and the sensitivity and specificity were 84.10%and 70.20%,respectively.For early-stage CRC,the AUC was 0.818,and the sensitivity and specificity were 76.30%and 72.30%,respectively.For advanced stage CRC,the AUC was 0.875,and the sensitivity and specificity were 81.80%and 72.30%,respectively.CONCLUSION MMP2,MMP7 and MMP 9 may exhibit diagnostic value for the early detection of CRC and may serve as auxiliary diagnostic markers for CRC.

Expressions of matrix metalloproteinases 1 and 3 and their tissue inhibitors in the conjunctival tissue and fibroblasts cultured from conjunctivochalasis

AIM：To investigate the expression of matrix metalloproteinases 1 and 3（MMP-1 and MMP-3） and their tissue inhibitors of metalloproteinases 1 and 3（ TIMP-1 and TIMP-3） in the conjunctiva of eyes with conjunctivochalasis（CCh）.METHODS：The conjunctival tissue was obtained from the CCh patients and controls,the MMPs/TIMPs expression concentration was determined by enzyme-linked immunosorbent assay（ELISA） and immunofluorescence staining.The expression levels of MMPs/TIMPs in the CCh fibroblasts were determined by analyzing its concentration in the cellular supernatant that was abstracted from the in vitro cultured CCh fibroblasts.RESULTS：MMP-1 and MMP-3 levels determined by ELISA were both significantly higher in the CCh group than that in the control group（P= 0.042,0.022,respectively）,so was the levels of TIMP-1（P= 0.010）.No significant difference in the expression of TIMP-3 in conjunctiva was found between the two groups（P= 0.298）.The expression of MMP-1 and MMP-3 were both up-regulated significantly in the CCh group（P= 0.040,0.001,respectively） on immunofluorescence staining.MMP-1 and MMP-3 expression in the fibroblasts were both significantly higher in the CCh group than that in the control group（P= 0.027,0.001,respectively）,while neither the TIMP-1 nor TIMP-3 expression was significantly different between the two groups（P= 0.421,0.237,respectively）.CONCLUSION：The overexpression of MMP-1 and MMP-3 in conjunctival tissue and fibroblasts may play an important role in the pathogenesis and development of CCh.

Serum matrix metalloproteinase 3 in detecting remitting seronegative symmetrical synovitis with pitting edema syndrome: A case report

We report a case of remitting seronegative symmetrical synovitis with pitting edema(RS3 PE) syndrome in a 71-year-old woman. She referred to our hospital with finger stiffness, edema of both hands and feet, pain of bilateral shoulder, wrist, metacarpophalangeal, proximal interphalangeal, and ankle joints. Rheumatoid factor was negative, human leukocyte antigen-B7 antigen was positive. Moreover, matrix metalloproteinase 3(MMP-3) was high. She was diagnosed with RS3 PE syndrome, and treatment with prednisolone(15 mg/d) was started. One week after prednisolone treatment initiation, CRP decreased to negative, and joint pain was almost completely resolved. However, hand stiffness persisted, and MMP-3 level was still high. Thus, prednisolone dose was increased to 20 mg/d, and the stiffness resolved. Twenty days after treatment initiation, MMP-3 was normalized. MMP-3 was more indicative of RS3 PE syndrome symptoms than CRP. Thus, MMP-3 seems to be more sensitive to RS3 PE syndrome symptoms.

The matrix metalloproteinase stromelysin-3 cleaves laminin receptor at two distinct sites between the transmembrane domain and laminin binding sequence within the extracellular domain

The matrix metalloproteinase (MMP) stromelysin-3 (ST3) has long been implicated to play an important role in extracellular matrix (ECM) remodeling and cell fate determination during normal and pathological processes. However like other MMPs, the molecular basis of ST3 function in vivo remains unclear due to the lack of information on its physiological substrates. Furthermore, ST3 has only weak activities toward all tested ECM proteins. Using thyroid hormone-dependent Xenopus laevis metamorphosis as a model, we demonstrated previously that ST3 is important for apoptosis and tissue morphogenesis during intestinal remodeling. Here, we used yeast two-hybrid screen with mRNAs from metamorphosing tadpoles to identify potential substrate of ST3 during development. We thus isolated the 37 kd laminin receptor precursor (LR). We showed that LR binds to ST3 in vitro and can be cleaved by ST3 at two sites distinct from where other MMPs cleave. Through peptide sequencing, we determined that the two cleavage sites are in the extracellular domain between the transmembrane domain and laminin binding sequence. Furthermore, we demon strated that these cleavage sites are conserved in human LR. These results together with high levels of human LR and ST3 expression in carcinomas suggest that LR is a likely in vivo substrate of ST3 and that its cleavage by ST3 may alter cell-extracellular matrix interaction, thus, playing a role in mediating the effects of ST3 on cell fate and behavior ob- served during development and pathogenesis.

EXPRESSION OF mRNA FOR MEMBRANE-TYPE 1, 2, AND 3 MATRIX METALLOPROTEINASES IN HUMAN LARYNGEAL CANCER

To investigate correlation of expressions of membrane-type 1, 2, and 3 matrix metalloproteinases (MT1, MT2, and MT3-MMP) to the invasion and metastases in laryngeal cancer. Methods Reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the mRNA level of MT1, MT2, and MT3-MMP in 24 patients with laryngeal cancer. The relationships of these three MT-MMP expressions to clinico-pathology were analyzed by statistics. Results The expressions of MT1, MT2, and MT3-MMP were significantly higher in laryngeal cancer tissues than those in para-tumorous tissues (P < 0.01) and had a close relationship with invasive depth (P < 0.05). But no significantly different expressions of these three MT-MMPs were found in different primary location and different histological grade of laryngeal cancer (P > 0.05). The expression of MT1-MMP was obviously higher in patients with metastatic lymph nodes than that in patients without metastatic lymph nodes (P < 0.05). Conclusion MT1, MT2, and MT3-MMP play an important role in the progression of laryngeal cancer, and MT1-MMP may serve as a reliable marker in estimating invasive and metastatic potency of laryngeal cancer. Suppressing expressions of MT1, MT2, and MT3-MMP early may inhibit the invasion and metastases of laryngeal cancer.

Expression pattern of matrix metalloproteinases-13 in a rat model of alcoholic liver fibrosis

BACKGROUND: Interstitial collagenase has been considered as an essential enzyme for collagenolysis in liver fi-brosis, because type Ⅰ and Ⅲ collagens increase predominantly in liver fibrosis. The present study aimed to demonstrate the gene expression of matrix metalloproteinases-13 (MMP-13) in the progressive phases of ethanol induced experimental liver fibrosis in rats. METHODS: Thirty-four Sprague-Dawley rats were randomly divided into two groups. The experimental group (24 rats) was given ethanol (44% , 7 g/kg) every day and the control group (10) was given normal saline. Liver samples were harvested from experimental rats at 4, 12 and 24 weeks respectively. The kinetics of MMP-13 mRNA expression was assayed by semi-quantity reverse transcriptase-poly-merase chain reaction (RT-PCR). RESULTS: In normal rat liver, a faint band for MMP-13 mRNA was observed by RT-PCR (0.24±0.41). The gene expression of MMP-13 was increased in the liver of the rats treated with ethanol for 4 weeks (0. 62 ±0. 54), but it was not considered statistically significant (P >0.05). And the livers from 12-week-treated rats showed a marked mRNA expression(1.65 ±0.47, P <0. 01). Once fibrosis became prominent (24 weeks), a faint band of MMP-13 mRNA was observed (0.39±0.25). CONCLUSION: MMP-13 participates in the degradation of newly-formed matrix in the early phase of rat liver fibrosis induced by ethanol, and it was induced in a distinct time frame.

Molecular Characterization and Expression Analysis of Matrix Metalloproteinase 3 in the Asian Yellow Pond Turtle Mauremys mutica

Matrix metallopeptidase 3 is a zinc-containing proteinase that participates in tissue remodeling and immune responses. In this study, a cDNA encoding matrix metallopeptidase 3 was isolated and characterized from the Asian yellow pond turtle Mauremys mutica（designated as MaMMP3）. The MaMMP3 cDNA is 1805 bp and consists of a 5＇-untranslated region（UTR） of 56 bp, a 3＇-UTR of 243 bp, and an open reading frame（ORF） of 1506 bp encoding 481 amino acids. Homology analysis of MaMMP3 revealed that the MaMMP3 shared 25%–63% similarity to other known MMP3 sequences. The genomic sequence covers 6007 bp. Comparative analysis of the cDNA sequence revealed that the Asian yellow pond turtle MMP3 has eight exons and seven introns. The phylogenetic tree showed that the MaMMP3 is closely related to Gallus gallus MMP3 and Taeniopygia guttata MMP3. The mRNA expression of the MaMMP3 in normal group without any bacterial challenge could be detected in all studied tissues including kidney, heart, live and spleen, with the highest level in the spleen. The results of immune challenge showed that the expression level of MaMMP3 was up-regulated in the spleen and liver. These results provided an important information for studying the roles of Asian yellow pond turtle MMP3 in immunity further.

Methanol extract of Codium fragile inhibits tumor necrosis factor-ɑ-induced matrix metalloproteinase-9 and invasiveness of MDA-MB-231 cells by suppressing nuclear factor-κB activation

Objective:To evaluate whether the methanol extract of Codium fragile(MECF) regulates tumor necrosis factor-α(TNF-α)-induced invasion of human breast cancer MDA-MB-231 cells by suppressing matrix metalloproteinase-9(MMP-9).Methods:Reverse transcriptionpolymerase chain reaction(RT-PCR) and western blot analysis were performed to analyze the expression of MMP-9 and nuclear factor-κB(NF-κB) subunits,p65 and p50,and IκB in MDA-MB-231 cells.3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide(MTT) assay was used for cell viability.MMP-9 activity and invasion were measured by gelatin zymography and a matrigel invasion assay,respectively.NF- κB activity was measured by an electrophoretic mobility shift assay and luciferase activity.Results:MECF had no effects on cell viability up to a concentration of 100 μg/mL in human breast cancer MDA-MB-231 cells regardless of the presence of TNF-α.MDA-MB-231 cells that were stimulated with TNF-α showed a marked increase of invasion compared to the untreated control,whereas pretreatment with MECF downregulated the TNF-α-induced invasion of MDA-MB-231 cells.Additionally,zymography,western blot analysis,and reverse transcriptase-polymerase chain reaction(RT-PCR) confirmed that MECF decreased TNF-α-induced MMP-9 expression and activity which is a key regulator for cancer invasion.According to an electrophoretic morbidity shift assay,pretreatment with MECF in MDA-MB-231 cells significantly decreased the TNF-α-induced DNA-binding activity of nuclear factor- κB(NF- κB),which is an important transcription factor for regulating cancer invasion-related genes such as MMP-9.Furthermore,treatment with MECF sustained the expression of p65 and p50 in response to TNF-α in the cytosolic compartment.The luciferase assay demonstrated that MECF attenuated TNF-α-induced NF- κB luciferase activity.Conclusion:MECF exhibited its antiinvasive capability by downregulating TNF-α-induced MMP-9 expression,resulting from the suppression of NF- κB activity in the human breast cancer cell line MDA-MB-231.

Serum Matrix Metalloproteinase 3 and Tissue Inhibitor Metalloproteinase 1 in Vascular Dementia: A Comparative Study

Aim: To compare serum level of matrix metalloproteinase 3 (MMP3) and tissue inhibitor metallo-proteinase 1 (TIMP1) in vascular dementia patients and healthy control subjects. Methods: A case control study was carried out in Ain Shams University hospital, Cairo, Egypt. 32 cases with vascular dementia were collected and classified into 2 subgroups;vascular dementia of multiinfarct type (VDMI) 14 patients, and vascular dementia of subcortical type (VDSC) 18 subjects. 23 cases with normal cognitive functions were collected as control group. Cases were subjected to comprehensive geriatric assessment, neurological examination, neuropsychological testing and brain CT scan. Blood sample was collected to analyze serum level of matrix metalloproteinase 3 (MMP3) and tissue inhibitor metalloproteinase 1 (TIMP1). Results: Mean serum level of TIMP1 (20.85 × 103 picogram/ml) was significantly lower than mean serum level of TIMP1 in control group (27.69 × 103 picogram/ml) (p = 0.018). The same finding was also evident when comparing VDMI subgroup mean serum TIMP1 (18.71 × 103 pc/ml) to control group (p = 0.025). There was no significant difference between mean serum MMP3 levels in cases group (mean = 67.39 × 103) as compared to control group (mean = 61.65 × 103 pc/ml) (p = 0.519). Conclusion: Patients with VD particularly VDMI has lower serum level of TIMP1 as compared to control group.

Lentinula edodes extract inhibits matrix metalloproteinase expression and increases typeⅠprocollagen expression via the p38 MAPK/c-Fos signaling pathway in ultraviolet A and B-irradiated HaCaT keratinocytes

Objective:To determine the effect of Lentinula edodes extract on ultraviolet(UV)A and UVB-induced changes in matrix metalloproteinase(MMP)and type I procollagen expression using human immortalized HaCaT keratinocytes.Methods:Lentinula edodes ethanol extract(LEE)was obtained by extraction with 80%ethanol for 4 h at 80℃.Effect of LEE on UVinduced alteration on the expression and production of MMPs and type I procollagen in keratinocytes was investigated using ELISA,RT-PCR,and Western blotting assay.To determine the underlying mechanism of LEE-mediated effects,mitogen-activated protein kinase(MAPK)and activator protein 1 signaling pathways were analysed by Western blotting assay.Results:LEE significantly inhibited the expression of MMP-1 and MMP-9 and increased the expression of type I procollagen in UVA and UVB-irradiated HaCaT keratinocytes.The phosphorylation levels of p38 were significantly inhibited by LEE whereas it did not affect c-Jun N-terminal kinase and extracellular signal-regulated kinase phosphorylation.Suppression of p38 phosphorylation was also accompanied by downregulation of UVA and UVB-induced increase in c-Fos.Conclusions:LEE effectively inhibits the expression of MMP-1 and MMP-9 and increases type I procollagen production through the p38 MAPK/c-Fos signaling pathway in UVA and UVB-irradiated HaCaT keratinocytes.This findings suggest that Lentinula edodes may be developed as a cosmetic material to suppress UV exposuremediated skin aging.

Association of Matrix Metalloproteinase-9 and p53 Gene Polymorphisms with Genetic Susceptibility to No-small-cell Lung Cancer

Matrix metalloproteinase-9（MMP-9） and p53 genes play an essential role in the multi-step process of tumorigenesis in lung cancer. Single nucleotide polymorphisms（SNPs） of MMP-9 and p53 genes are associated with the risk and progression of many cancers. In this study, we evaluated the association of the R279Q polymorphism of MMP-9 or the A1/A2 polymorphism of p53 gcne with the risk of no-small-cell lung cancer（NSCLC） in Han population of Northeast China. We examined the frequency of SNPs in the two kinds of genes of 50 patients with NSCLC and 50 cancer-free controls frequency-matched by age and sex. Polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） technique was used to determine the genotypes. The results indicate that the 279RR genotype in MMP-9 gene and the A1/A2 genotype in p53 gene show a significantly increased risk of NSCLC. Therefore, the MMP-9 279RR and p53 A1/A2 genotypes may be used as markers for susceptibility to NSCLC in Han population of Northeast China.

乳腺癌组织中TIMP-3及DNMT1的表达与患者预后的相关性

目的:分析研究乳腺癌患者中基质金属蛋白酶组织抑制因子3(TIMP-3)及DNA甲基转移酶1(DNMT1)的表达水平与患者临床预后的相关性。方法:收集58例临床资料完整的乳腺癌手术切除标本,采用免疫组化SP法检测癌组织及相应癌旁组织中TIMP-3、DNMT1、ER、PR、HER-2、p53、Ki-67的表达,将TIMP-3、DNMT1表达水平与临床病理参数及随访生存状况进行相关性分析,所有入组患者均进行随访5年以上。结果:我们发现,在乳腺癌组织中,TIMP-3呈低表达,DNMT1呈高表达,TIMP-3及DNMT1的表达呈负相关;TIMP-3表达水平与Ki-67呈负相关,DNMT1表达水平与Ki-67呈正相关,与其他临床病理参数未见相关性。Cox风险比例模型分析显示只有临床分期和DNMT1表达水平是影响总生存期(OS)和无病生存期(DFS)的独立风险因素。TIMP-3低表达组的5年OS和DFS均显著低于高表达组,DNMT1高表达组的5年OS和DFS均显著低于低表达组。结论:研究表明乳腺癌中TIMP-3及DNMT1表达水平与肿瘤细胞恶性表型及患者生存时间有关,可能成为判断乳腺癌预后的一项重要指标,并作为治疗计划制定的依据。

类风湿关节炎患者血清SAA、CCL20、MMP-3表达水平及临床意义

目的探讨类风湿关节炎(RA)患者血清淀粉样蛋白A(SAA)、趋化因子配体20(CCL20)及基质金属蛋白酶3(MMP-3)水平变化及临床意义。方法回顾性选取2020年9月至2023年1月大同市第五人民医院收治的RA患者108例作为研究对象,依据28个关节的疾病活动度评分(DAS28)评分,将患者分为缓解期组(n=35,DSA28评分<2.6)与活动期组(n=73,DSA28评分≥2.6),并将活动期患者进一步分为轻度活动期(n=20,DSA28评分2.6~3.2)、中度活动期(n=29,DSA28评分>3.2~5.1)与重度活动期(n=24,DSA28为>5.1);另选取同期健康体检者80名作为对照组。所有受试者均检测血清SAA、CCL20、MMP-3水平。比较不同组别血清SAA、CCL20、MMP-3水平;使用Pearson相关分析血清SAA、CCL20、MMP-3水平与红细胞沉降率(ESR)、C反应蛋白(CRP)的相关性;使用受试者工作特征(ROC)曲线评价各指标对RA疾病活动度的诊断价值。结果RA组血清SAA、CCL20、MMP-3水平分别为(42.25±13.46)mg/L、(45.69±12.78)pg/mL、(85.41±25.14)ng/mL,均显著高于对照组[(7.14±2.12)mg/L、(18.12±5.47)pg/mL、(27.36±8.21)ng/mL],差异均有统计学意义(P<0.05)。RA活动期组患者血清SAA、CCL20、MMP-3水平分别为(51.78±10.71)mg/L、(53.14±10.45)pg/mL、(106.10±20.39)ng/mL,显著高于缓解期组[(22.37±7.14)mg/L、(30.15±8.24)pg/mL、(42.25±13.64)ng/mL],差异均有统计学意义(P<0.05)。重度活动度组血清SAA、CCL20、MMP-3水平均高于中度活动度组和轻度活动度组,差异均有统计学意义(P<0.05),随着疾病活动度提高,血清SAA、CCL20、MMP-3水平逐渐增高。Pearson相关分析显示,活动期RA患者血清SAA、CCL20、MMP-3水平与CRP、ESR均呈正相关(P<0.05)。ROC曲线分析得出,血清SAA、CCL20、MMP-3区分RA轻度活动度与中度活动度的曲线下面积(AUC)分别为0.852、0.756、0.725,区分中度活动度与重度活动度的AUC分别为0.852、0.756、0.725,均显示出一定的诊断能力。结论RA患者血清SAA、CCL20、MMP-3水平均呈高表达,这3项指标可作为评估疾病活动度的生物标志物,可为临床预测病情进展提供参考。

基质金属蛋白酶-13在多发性骨髓瘤中的作用研究

目的:探讨基质金属蛋白酶-13(MMP-13)在多发性骨髓瘤(MM)疾病发生发展及病情判断、预后评估等方面的作用。方法:收集MM患者57例、正常对照人群45例,采用实时荧光定量PCR检测研究对象MMP-13基因mRNA表达水平,比较MM患者组和正常对照组MMP-13 mRNA表达水平的差异,分析MMP-13与MM骨病及其严重程度、ISS分期、DS分期及治疗效果的关系。结果:MM患者MMP-13mRNA表达水平较正常对照组显著升高(P<0.05);有骨病的MM患者较无骨病的患者MMP-13 mRNA明显升高,且骨病越严重升高越明显(P<0.05);ISS分期及DS分期Ⅰ期与Ⅲ期患者之间MMP-13 mRNA差异也有统计学意义(P<0.05);患者治疗后较治疗前MMP-13明显下降(P<0.05)。结论:MMP-13基因mRNA表达水平与MM发生发展相关,其表达水平在病情判断、预后评估等方面具有一定的指导意义。

慢性肾脏病患者血清CHI3L1、MMP-13表达水平及其病情评估、预后价值

目的探讨慢性肾脏病患者血清几丁质酶3样蛋白1(CHI3L1)、基质金属蛋白酶-13(MMP-13)表达水平及病情评估、预后价值。方法选取2020年3月至2022年8月在江油市人民医院就诊的208例慢性肾脏病患者作为病例组,按照病情严重程度将208例慢性肾脏病患者分为Ⅰ期组21例、Ⅱ期组42例、Ⅲ期组86例、Ⅳ期组38例、Ⅴ期组21例。另选取同期152例体检健康者作为对照组。根据患者预后情况将208例患者分为预后良好组(n=92)及预后不良组(n=116)。收集受试人员一般资料,采用酶联免疫吸附试验检测血清CHI3L1、MMP-13表达水平,Pearson法分析慢性肾脏病患者血清CHI3L1、MMP-13表达水平的相关性,以及二者与肾小球滤过率(GFR)的相关性,采用Cox回归分析影响慢性肾脏病患者预后的因素。结果对照组、病例组年龄、性别等一般资料比较,差异无统计学意义(P>0.05);病例组患者血清中CHI3L1表达水平较对照组显著增加,但MMP-13表达水平显著降低,差异有统计学意义(P<0.05);随着病情分期增加,患者血清CHI3L1表达水平随之增加,MMP-13表达水平随之降低(P<0.05);预后不良组患者血清CHI3L1表达水平较预后良好组显著增加,MMP-13表达水平显著降低(P<0.05);Pearson法分析显示,慢性肾脏病患者血清CHI3L1、MMP-13表达水平呈负相关,CHI3L1表达水平与GFR呈负相关,MMP-13表达水平与GFR呈正相关(P<0.05)。Cox回归分析显示,血清CHI3L1、MMP-13、GFR为慢性肾脏病患者预后不良的独立影响因素(P<0.05)。结论慢性肾脏病患者血清CHI3L1表达水平升高,MMP-13表达水平降低,二者均可用于病情及预后评估。

血清MMP1和P53自身抗体联合检测对食管鳞状细胞癌的诊断价值

目的:探讨食管鳞状细胞癌(ESCC)患者血清基质金属蛋白酶1(MMP1)和P53自身抗体表达水平及其联合检测的诊断意义。方法:收集2013年3—9月在汕头大学医学院附属肿瘤医院住院治疗的93例ESCC患者,并以同期90例体检者为正常对照组。应用酶联免疫吸附实验(ELISA)检测两组对象血清MMP1和P53自身抗体的表达水平,采用受试者工作特征(ROC)曲线评价诊断效能。结果:血清MMP1含量和P53自身抗体滴度在ESCC组分别为(8.076±5.912)ng/mL和0.291±0.492,正常对照组分别为(4.652±3.346)ng/mL和0.055±0.037,ESCC组均较正常对照组显著升高(均为P<0.01)。ROC曲线分析显示,MMP1诊断ESCC的曲线下面积(AUC)为0.700(95%CI为0.624~0.776),当取最佳诊断截断值7.248 ng/mL时,特异度为83.3%,敏感度为52.7%。P53自身抗体诊断ESCC的AUC为0.713(95%CI为0.638~0.788),诊断截断值为0.080,特异度为83.3%,敏感度为49.5%。两者联合检测诊断ESCC的AUC为0.787(95%CI为0.720~0.854),特异度为83.3%,敏感度为66.7%,优于单独使用MMP1或P53自身抗体。在早期ESCC中,MMP1和P53自身抗体联合检测亦能获得较好的诊断效能,AUC为0.760,95%CI为0.663~0.857,特异度为83.3%,敏感度为66.7%。结论:ESCC患者血清MMP1和P53自身抗体水平均升高,二者联合检测有助于ESCC的早期诊断,可作为ESCC的诊断标志物。

3D打印技术用于经鼻蝶窦入路垂体腺瘤切除术应用效果及对血清MMP-9和IGF-1水平的影响

目的:探究3D打印技术在经鼻蝶窦入路垂体腺瘤(PA)切除术的应用效果及对血清基质金属蛋白酶-9(MMP-9)和胰岛素样生长因子-1(IGF-1)水平的影响。方法:选取2020年5月至2022年5月秦皇岛市第一医院收治的84例PA患者,按照随机数表法将其分为观察组和对照组,每组42例。对照组行经鼻蝶窦入路垂体腺瘤切除术,观察组行经鼻蝶窦入路垂体腺瘤切除术联合应用3D打印技术,比较两组肿瘤切除效果、围术期指标、视力改善情况、MMP-9和IGF-1水平,以及鼻腔功能的鼻气道阻力(NAR)、T&T嗅觉测试评分及并发症。结果:观察组肿瘤切除效果优于对照组,差异有统计学意义(U=2.286,P<0.05);观察组手术时间、术中出血量及住院时间均少于对照组,差异有统计学意义(t=4.780、11.438、11.842,P<0.05);术后3 d、7 d时观察组血清MMP-9和IGF-1水平低于对照组,差异有统计学意义(F=7.526、4.985,P<0.05);术后1个月、3个月时观察组NAR及T&T嗅觉测试评分低于对照组,差异有统计学意义(F=6.359、8.436,P<0.05);两组视力视野改善情况及并发症发生率比较,差异无统计学意义(P>0.05)。结论:3D打印技术用于经鼻蝶窦入路垂体腺瘤切除术可提高肿瘤切除效果,优化手术操作,减少创伤,有利于减轻疼痛,改善嗅觉功能与视力视野,并能降低血清MMP-9、IGF-1水平,且安全性较高。

超声联合血清AnxA1、MMP-3对NSTE-ACS患者PCI术后冠状动脉再狭窄的预测价值

目的探讨血清膜联蛋白A1(AnxA1)、基质金属蛋白酶-3(MMP-3)联合冠状动脉血管内超声钙化特征对非ST段抬高型急性冠脉综合征(NSTE-ACS)患者经皮冠状动脉介入治疗(PCI)术后冠状动脉再狭窄的预测价值。方法回顾性选取2019年7月至2022年5月鄂州市中心医院行PCI治疗的236例NSTE-ACS患者为研究对象,依据随访1年内冠状动脉再狭窄情况分为再狭窄组(n=24)和非狭窄组(n=212)。收集患者临床资料,对比患者血清AnxA1、MMP-3水平、血管内超声检查结果;采用Logistic多因素回归分析NSTE-ACS患者PCI术后冠状动脉再狭窄影响因素;受试者操作特征(ROC)曲线分析血清AnxA1、MMP-3水平联合钙化特征评分预测术后冠状动脉再狭窄的价值。结果再狭窄组血清AnxA1、MMP-3水平及钙化病变比例、浅表型钙化比例、钙化弧度、钙化长度、钙化特征评分分别为(2.40±0.61)μg/L、(56.49±12.31)μg/L、66.67%、70.83%、(162.18±28.43)°、(25.91±4.56)mm、(5.02±1.28)分,高于非狭窄组[(1.78±0.40)μg/L、(42.78±10.07)μg/L、22.64%、29.72%、(78.41±20.39)°、(13.72±3.68)mm、(3.47±1.02)分],差异均有统计学意义(P<0.05)。AnxA1、MMP-3、钙化特征评分是NSTE-ACS患者PCI术后冠状动脉再狭窄的独立危险因素(P<0.05)。AnxA1、MMP-3、钙化特征评分及3者联合预测NSTE-ACS患者PCI术后冠状动脉再狭窄的AUC分别为0.825、0.780、0.854、0.960。结论AnxA1、MMP-3、钙化特征评分是NSTE-ACS患者PCI术后冠状动脉再狭窄的独立危险因素,3者联合较单一指标对冠状动脉再狭窄的预测价值更高。