Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis

BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.

血清TLR4、TIMP-1水平与小儿热性惊厥临床特征的关系及对继发癫痫的预测价值

目的分析血清Toll样受体4(TLR4)、基质金属蛋白酶组织抑制剂(TIMP)-1水平与小儿热性惊厥(FC)临床特征的关系及对FC继发癫痫的预测价值。方法选取2019年1月至2022年6月320例FC患儿作为研究组,另选取同期发热无惊厥儿童150例作为发热组,体检健康儿童150例作为对照组。根据FC患儿是否继发癫痫分为癫痫组和无癫痫组。采用酶联免疫吸附试验检测血清TLR4、TIMP-1水平,采用Pearson相关分析TLR4、TIMP-1水平及与临床指标间的相关性。采用受试者工作特征(ROC)曲线分析血清TLR4、TIMP-1预测FC继发癫痫的价值。采用Logistic回归分析FC患儿继发癫痫的影响因素。结果FC患儿、发热无惊厥儿童、体检健康儿童血清TLR4、TIMP-1水平依次降低,且两两比较,差异均有统计学意义(P<0.05)。研究组与发热组围生期异常发生情况、肿瘤坏死因子α(TNF-α)、C-反应蛋白(CRP)、白细胞介素-1β(IL-1β)水平和振幅整合脑电图(AEEG)评分比较,差异均有统计学意义(P<0.05)。癫痫组患儿血清TLR4、TIMP-1水平明显高于无癫痫组(P<0.05)。癫痫组和无癫痫组患儿首次惊厥次数、惊厥持续时间、首次惊厥前发热时间、围生期异常发生情况、TNF-α、CRP、IL-1β水平和AEEG评分比较,差异均有统计学意义(P<0.05)。血清TLR4水平与TIMP-1呈正相关(P<0.05);血清TLR4、TIMP-1水平与TNF-α、CRP、IL-1β呈正相关(P<0.05),与AEEG评分呈负相关(P<0.05)。TLR4、TIMP-1联合预测FC患儿继发癫痫的曲线下面积(AUC)明显高于单项检测的AUC(Z_(TLR4-联合)=3.016,P=0.003;Z_(TIMP-1-联合)=2.232,P=0.026)。Logistic回归分析结果表明,TLR4、TIMP-1、TNF-α、CRP、IL-1β水平升高,AEEG评分降低均为FC继发癫痫的危险因素(P<0.05)。结论血清TLR4、TIMP-1与FC患儿临床特征密切相关,TLR4、TIMP-1可能是FC继发癫痫的影响因素。

多西他赛联合PD-1抑制剂对晚期非小细胞肺癌预后及血清MMP-9、TIMP-1水平的影响

目的探讨多西他赛联合程序性死亡受体1(PD-1)抑制剂对晚期非小细胞肺癌(NSCLC)预后及血清基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制剂-1(TIMP-1)水平的影响。方法将90例晚期NSCLC患者随机分为研究组和对照组,每组45例。对照组给予多西他赛和顺铂治疗,研究组在对照组治疗基础上给予PD-1治疗,3周为1个治疗周期,共治疗6个周期。比较2组治疗后客观缓解率(ORR)、疾病控制率(DCR)、无进展生存期(PFS)、总生存期(OS),观察2组治疗期间不良反应发生情况及治疗前后血清MMP-9、TIMP-1水平的变化。结果研究组治疗后DCR、PFS、OS显著高于对照组(P<0.05);治疗期间2组不良反应发生率比较差异无统计学意义(P>0.05);2组治疗后血清MMP-9、TIMP-1水平较治疗前显著降低(P<0.05),且研究组降低较对照组更为显著(P<0.05)。结论多西他赛联合PD-1抑制剂对晚期NSCLC具有较好的疗效和预后,能够降低血清MMP-9、TIMP-1水平,降低肺癌细胞侵袭转移的能力,安全性良好。

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in early focal cerebral infarction following urokinase thrombolysis in rats

Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion, and is associated with cerebral microvascular permeability, blood-brain barrier destruction, inflammatory cell infiltration and brain edema. Matrix metalloproteinase-9 also likely participates in thrombolysis. A rat model of middle cerebral artery infarction was established by injecting autologous blood clots into the internal carotid artery. At 3 hours following model induction, urokinase was injected into the caudal vein. Decreased neurological severity score, reduced infarct volume, and increased expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were observed in the cerebral cortex 24 hours after urokinase thrombolysis. These results suggest that urokinase can suppress damage in the acute-early stage of cerebral infarction.

Expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in ulcerative colitis

AIM: To examine the expression of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with ulcer- ative colitis (UC). METHODS: Reverse transcription-polymerase chain re- action (RT-PCR) and immunohistochemistry were used to study the expression of MMP-1 and TIMP-1 at both mRNA and protein levels in patients with UC and con- trols. The relationship between MMP-1 mRNA, TIMP-1 mRNA, MMP-1 mRNA/TIMP-1 mRNA ratio and the sever- ity of clinical symptoms of the patients with UC were also analyzed. RESULTS: The expression of MMP-1 mRNA and TIMP-1 mRNA in the ulcerated and inflamed colonic mucosa was signifi cantly higher than that in the non-inflamed colonic mucosa (P < 0.001), but there was no statistically signif i- cant difference in the non-inflamed colonic mucosa of UC patients and normal controls (P > 0.05). The mRNA ex- pression of MMP-1 and TIMP-1 in ulcerated colonic mu- cosa of UC patients was increased by 80-fold and 2.2-fold, respectively when compared with the normal controls. In the inflamed colonic mucosa, the increase was 30-fold and 1.6-fold, respectively. Immunohistochemical analy- sis showed that among the ulcerated, inflamed, and non-inflamed colonic mucosae of UC patients and the normal controls, the positive rate of MMP-1 expression was 87%, 87%, 40% and 35% respectively, and the positive rate of TIMP-1 expression was 89%, 89%, 80% and 75%, respectively. Furthermore, the expression of MMP-1 mRNA, TIMP-1 mRNA and the MMP-1 mRNA/ TIMP-1 mRNA ratio were correlated with the severity of clinical symptoms (P <0.05).CONCLUSION: Excessive expression of MMP-1 in the diseased colonic mucosa causes excessive hydrolysis of the extracellular matrix (ECM) and ulceration in UC pa-tients. MMP-1 mRNA, TIMP-1 mRNA and MMP-1 mRNA/ TIMP-1 mRNA ratio can be used as biomarkers to judge the severity of clinical symptoms in patients with UC. Exogenous TIMP-1 or MMP-1 inhibitor therapy is a novel treatment for patients with UC.

Expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic stellate cells during rat hepatic fibrosis and its intervention by IL-10

AIM: To investigate the expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic fibrosis and the antifibrogenic role of exogenous interleukin-10 (IL-10).METHODS: Hepatic fibrosis was induced by CCl4administration and 60 male Sprague-Dawley rats were randomly divided into normal control group (group N, 8rats), CCl4-induced group (group C, 28 rats) and IL-10-treated group (group I, 24 rats). At the beginning of the 7th and 11th wk, rats in each group were routinely perfused with pronase E and type Ⅳ collagenase through portal vein catheter and the suspension was centrifuged by 11%Nycodenz density gradient to isolate hepatic stellate cells (HSCs). RT-PCR was used to analyze mRNA of MMP-2 and TIMP-1 from freshly isolated cells. Densitometric data were standardized with β-actin signals. Immunocytochemistry was performed to detect MMP-2 and TIMP-1 expression in HSC cultured for 72 h.RESULTS: Compared to group N in the 7th wk, MMP-2and TIMP-1 mRNA increased in group C (P= 0.001/0.001)and group I (P = 0.001/0.009). The level of MMP-2 and TIMP-1 mRNA in group I was significantly lower than that in group C (P= 0.001/0.001). In the 11th wk, MMP-2 mRNAin group I was still lower than that in group C (P = 0.005),but both dropped compared with that in the 7th week (P = 0.001/0.004). TIMP-1 mRNA in group I was still lower than that in group C (P= 0.001), and increased in group C (P = 0.001) while decreased in group I (P = 0.042)compared with that in the 7th wk. Same results were found by immunocytochemistry.CONCLUSION: Expression of MMP-2 and TIMP-1 is increased in hepatic fibrosis. IL-10 exhibits an antifibrogenic effect by suppressing MMP-2 and TIMP-1 expression.

Correlation of matrix metalloproteinase－2, －9, tissue inhibitor－1 of matrix metalloproteinase and CD44 variant 6 in head and neck cancer metastasis

This study aimed to explore the molecular mechanism in tumor invasion and metastasis. The ex-pression of matrix metalloproteinase-2,-9 (MMP-2,MMP-9), tissue inhibitor-1 of matrix metalloprote inase(TIMP-1) , cell adhesion molecule 44 variant 6 (CD44v6) , HER2/neu and p53 was investigated in 154 pa-tients with head and neck squamous cell carcinoma (SCC) by ABC and ImmunoMax immunohistochemical method. Their clinical relevance and correlation were analysed. The expression of MMP-2, MMP-9, TIMP-1,CD44v6, HER2/neu and p53 was found in cancer cells in 87.01%, 85.71%, 68. 18%, 98.05%,55.19% and 50.65% cases respectively. Linear regression and correlation analysis revealed that there wasclose positive relationship ( P < 0.05) between the expression of MMP-2 and MMP-9, TIMP-1 and CD44v6,HER2/neu and MMP-9, MMP-2 and p53. Up-regulation of MMP-2 was accompanied by advanced T stage( P < 0.01 ) . There was also a trend of MMP-2 expression being related with tumor metastasis. Increased ex-pression of HER2/neu was found in patients with tumor recurrence( P < 0.05 ) . The expression of TIMP-1 washigher in laryngeal cancer than that in pharyngeal cancer, and higher in keratinizing and non-keratlnizing SCC than that in basaloid SCC ( P < 0.05 ) . These findings suggested that MMP-2 and MMP-9, HER2/neu andMMP-9, MMP-2 and p53 had a coordinate function in aggression of tumor; that MMP-2 had a more important function than MMP-9 in tumor invasion and metastasis; and that HER2/neu might serve as a biomarker forpoor prognosis in HNSCC.

虎黄烧伤搽剂联合常规疗法治疗Wagner 1-2级糖尿病足临床观察

目的探讨虎黄烧伤搽剂联合常规疗法治疗Wagner 1-2级糖尿病足的临床疗效。方法选取重庆医科大学附属大足医院2022年1月至2023年6月收治的Wagner 1-2级糖尿病足患者94例,按随机数字表法分为对照组和观察组,各47例。两组患者均予常规降糖药物,并以蚕食清创法清除坏死组织;观察组患者加用虎黄烧伤搽剂治疗。两组均连续治疗28 d。结果观察组疗效优于对照组(P<0.05);观察组糖尿病足感染率为2.13%,显著低于对照组的14.89%(P<0.05)。与对照组比较,观察组患者治疗第7,14,28天创面面积显著缩小,创面愈合时间显著缩短,创面组织中血管内皮生长因子(VEGF)、表皮生长因子(EGF)、基质金属蛋白酶抑制剂-1(TIMP-1)、转化生长因子-β(TGF-β)水平均显著升高,基质金属蛋白酶-9(MMP-9)水平显著降低(P<0.05)。结论虎黄烧伤搽剂联合常规疗法治疗Wagner 1-2级糖尿病足,可进一步上调创面组织中VEGF,EGF,TIMP-1,TGF-β水平,降低MMP-9水平,加速创面愈合。

血清TIMP-1、VEGF水平对自然分娩初产妇产后压力性尿失禁严重程度的预测价值

目的探讨自然分娩初产妇血清基质金属蛋白酶组织抑制因子-1(tissue inhibitorof metall oproteinase-1,TIMP-1)、血管内皮生长因子(vascular endothelial growth factor,VEGF)水平对产后压力性尿失禁(post partum stress uri-nary incontinence,PSUI)严重程度的预测价值。方法选取2019年12月至2023年7月220例PSUI自然分娩初产妇为病例组,根据尿垫试验结果分为轻度组158例和中重度组62例。另纳入同期220例无PSUI的自然分娩初产妇作为对照组。采用ELISA法检测入组者血清TIMP-1、VEGF水平;采用PearSon法分析PSUI患者血清TIMP-1与VEGF的相关性;采用多因素Logistic回归分析PSUI患者疾病严重程度的影响因素;采用受试者工作特征曲线分析血清TIMP-1、VECF对PSUI患者疾病严重程度的预测价值。结果病例组血清TIMP-1水平显著低于对照组,血清VECF水平显著高于对照组(P<0.01)。中重度组血清TIMP-1水平显著低于轻度组,血清VEGF水平、年龄≥35岁比例、新生儿体质量显著高于轻度组(P<0.05,P<0.01)。PSUI患者血清TIMP-1与VEGF呈负相关(r=-0.671,P<0.05)。TIMP-1是PSUI患者疾病程度加重的保护因素(P<0.01),VEGF是PSUI患者疾病程度加重的危险因素(P<0.01)。TIMP-1、VECF单独及联合预测PSUI患者疾病严重程度的曲线下面积(area under curve,AUC)分别为0.857、0.808、0.901,其中联合预测的AUC高于二者单独预测(P<0.01)。结论PSUI患者血清TIMP-1低表达,VECF高表达,且TIMP-1、VECF与病情程度密切相关,二者联合在预测PSUI患者疾病严重程度方面有较高的价值。

Expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in malignant peripheral nerve sheath tumor

BACKGROUND： Matrix metalloproteinase-9 （MMP-9） can degrade collagen IV （the main structural ingredient of basilar membrane）, and it also plays an important role in tumor vascularization, tumor cell progression, formation of metastatic focus, etc. Tissue inhibitor of metalloproteinase-1 （T1MP-1） can bind with MMP-9 to form 1 ： 1 compound and inhibit its activity, and can negatively regulate the tumor progression and metastasis. OBJECTIVE： To analyze the relationship of MMP-9 and T1MP-1 expressions with the pathological grade, metastasis and prognosis of malignant peripheral nerve sheath tumor （MPNST）. DESIGN： An observational comparative experiment. SETTING： Heze Medical College. PARTICIPANTS： Fifty-eight surgical pathological samples, which were clearly diagnosed to be MPNST, were collected from the pathological laboratory archives in the Department of Pathology, Heze Municipal Hospital from January 1988 to December 2003. The MPNST pathological types were common tumor in 53 cases, malignant triton tumor in 2 cases, epithelial MPNST in 2 cases and MPNST with gland differentiation in 1 case. The pathological grade was grade 1 in 11 cases, grade 2 in 24 cases and grade 3 in 23 cases. Besides, the resected tumor samples of 20 patients with benign peripheral nerve tumor （10 cases of nerve sheath tumor and 10 cases of neurofibromatosis） and the normal peripheral nerves （by-products of some surgeries） of 5 patients were also collected. The samples were used with the approval of the patients. Rat-anti-human MMP-9, TIMP-1 monoclonal antibody and S-P kit were purchased from Fuzhou Maixin Biotechnology, Co.,Ltd. METHODS： The documented paraffin blocks were again prepared to sections of 5 lJ m. The expressions of MMP-9 and TIMP-1 in the samples were detected with mmunohistochemical S-P method. The relationships of the MPNST severity, recurrence, metastasis and survival rate with the expressions of MMP-9 and TIMP-1 were analyzed. MAIN OUTCOME MEASURES： Relationships of MMP-9 and TIMP-1 expressions with the MPNST severity and prognosis. RESULTS： ①Expressions of MMP-9 and TIMP-1 in three tissues： MMP-9 and TIMP-1 stainings were mainly observed in cytoplasm. Among the 58 MPNST patients, the MMP-9 expression was significantly higher than those in normal peripheral nerve and benign tumor （P 〈 0.05）, while the TIMP-1 expression in MPNST was lower than those in normal peripheral nerve and benign tumor （P 〈 0.05）. ②Relationship of MMP-9 and TIMP-1 expressions with the severity and prognosis of MPNST： The expressions of both proteins were observed in the four subtypes. The positive expression of MMP-9 in the MPNST patients of grades 2 - 3 was significantly higher than that in the MPNST patients of grade 1 （P 〈 0.05）, while the expression of MMP-9 was significantly lower than that in the MPNST patients of grade 1 （P 〈 0.05）. The metastatic rate was positively correlated with MMP-9 expression （r =1.696, P 〈 0.05）, but negatively correlated with TIMP-1 expression （r = - 2.125, P 〈 0.05）. CONCLUSION： MMP-9 and TIMP-1 are associated with MPNST pathological grades and metastasis, and can be used as the indicators for judging the severity and orognosis of MPNST.

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.

CTA联合血清MMP-9、TIMP-1对脑梗死患者颈动脉斑块诊断价值

目的探究计算机断层扫描血管成像(CTA)联合血清基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制剂-1(TIMP-1)对脑梗死患者颈动脉斑块诊断价值。方法选取2021年5月-2021年12月期间我院神经内科收治的140例脑梗死患者作为试验组研究对象,另选择同期至我院进行体检的健康者80例作为参照组。试验组患者均行CTA和数字减影血管造影(DSA),分析CTA诊断颈动脉斑块价值。试验组和参照组均接受血清MMF-9 TIMP-1检测。对比试验组与参照组的血清MMP-9、TIMP-1水平差异。在试验组中,以DSA为金标准,将患者分为斑块组和无斑块组,对比两组之间的血清MMP-9、TIMP-1水平差异,对CTA联合血清MMP-9、TIMP-1诊断颈动脉斑块的效果进行受试者特征曲线(ROC)分析。结果CTA检测结果显示存在颈动脉斑块者64例,无斑块组76例,CTA诊断颈动脉斑块敏感度为96.88%,特异性为97.37%,准确度为97.14%;试验组血清MMP-9水平显著高于参照组(P<0.05),TIMP-1水平显著低于参照组(P<0.05);斑块组血清MMP-9水平显著高于无斑块组(P<0.05),TIMP-1水平显著低于无斑块组(P<0.05);ROC曲线显示血清CTA、MMP-9、TIMP-1水平单独及联合诊断颈动脉斑块AUC值依次为0.979、0.835、0.812和0.993。结论CTA联合血清MMP-9、TIMP-1对脑梗死患者颈动脉斑块具有良好的诊断价值。

脑脊液基质金属蛋白酶9水平和基质金属蛋白酶9/基质金属蛋白酶组织抑制剂1比值与结核性脑膜炎病情严重程度的相关性及对预后的预测价值研究

目的 探讨脑脊液基质金属蛋白酶9(MMP-9)水平和MMP-9/基质金属蛋白酶组织抑制剂1(TIMP-1)比值与结核性脑膜炎病情严重程度的相关性及对预后的预测价值。方法 选择2021年1月至2023年2月在湖南省胸科医院住院的结核性脑膜炎患者72例为观察组,以同期住院的非肿瘤非感染性头痛患者52例为对照组。比较2组患者脑脊液MMP-9水平和MMP-9/TIMP-1比值。根据改良的英国医学研究理事会结核性脑膜炎分期标准将观察组患者分为Ⅰ期组、Ⅱ期组、Ⅲ期组,比较3组患者MMP-9水平和MMP-9/TIMP-1比值。根据预后情况将观察组患者分为预后良好组和预后不良组,比较2组MMP-9水平和MMP-9/TIMP-1比值,并以受试者工作特征(ROC)曲线法评估各指标对结核性脑膜炎的预后预测价值。结果 观察组MMP-9水平及MMP-9/TIMP-1比值均大于对照组[(96±21)μg/L比(50±12)μg/L、(1.21±0.33)比(0.67±0.15)](均P<0.05),但2组间TIMP-1水平比较差异无统计学意义(P>0.05)。不同严重程度结核性脑膜炎患者MMP-9水平及MMP-9/TIMP-1比值差异均有统计学意义,且均呈Ⅰ期<Ⅱ期<Ⅲ期(均P<0.05);不同严重程度结核性脑膜炎患者TIMP-1水平差异均无统计学意义(均P>0.05)。相关性分析结果显示,结核性脑膜炎病情严重程度与MMP-9水平及MMP-9/TIMP-1比值均呈正相关(r=0.861、P=0.012;r=0.731、P=0.008),与TIMP-1无相关性(r=0.220,P=0.063)。预后不良组患者MMP-9水平及MMP-9/TIMP-1比值均高于预后良好组(均P<0.05),2组TIMP-1水平差异无统计学意义(P>0.05)。ROC曲线分析结果显示,MMP-9水平、MMP-9/TIMP-1比值预测结核性脑膜炎患者预后不良的截断值分别为112.04μg/L、1.41,曲线下面积分别为0.803、0.905(均P<0.05)。结论 结核性脑膜炎患者脑脊液MMP-9水平、MMP-9/TIMP-1比值明显升高,且MMP-9水平、MMP-9/TIMP-1比值与结核性脑膜炎的病情严重程度呈正相关,并可用于预测患者预后。

CTA联合血清MMP-9、TIMP-1在缺血性脑卒中诊断中的应用

目的 探究CT血管成像(CTA)联合血清基质金属蛋白酶9(MMP-9)、金属蛋白酶组织抑制因子1(TIMP-1)在缺血性脑卒中诊断中的应用。方法 选取2021年5月至2022年5月期间张家口市第一医院神经内科收治的140例脑卒中患者作为研究组研究对象,均行CTA检查,以数字血管造影(DSA)为金标准,分析CTA对缺血性脑卒中诊断价值,另选择同期至此院进行体检的健康者80名作为对照组,比较两组患者血清MMP-9、TIMP-1水平。结果 140例患者,共检查463条头颈血管,经CTA诊断无狭窄236条、轻度狭窄66条、中度狭窄36条、重度狭窄46条、闭塞22条,与DSA对照CTA诊断缺血性脑卒中患者血管狭窄程度的灵敏度为81.25%,特异度为90.15%;CTA诊断轻度狭窄患者74例、中度16例、重度46、闭塞4例,与DSA对照CTA诊断灵敏度82.50%、特异度83.33%;研究组患者血清MMP-9、TIMP-1表达水平均显著高于对照组患者,差异有统计学意义(t=73.668、33.925,P<0.05),且研究组患者随着狭窄程度增加,血清MMP-9、TIMP-1水平逐渐上升,差异有统计学意义(F=13298.37、901.001,P<0.05);MMP-9以247.14 ng/mL为临界值,阳性53例,阴性87例;TIMP-1均值(239.21 ng/mL)为临界值,阳性53例,阴性87例;以CTA阳性为基础,MMP-9、TIMP-1任一指标阳性则定义为联合诊断阳性,结果显示联合诊断灵敏度为88.75%,特异度为80.00%。结论 CTA联合血清MMP-9、TIMP-1对缺血性脑卒中诊断效能较高,临床应在密切观察缺血性脑卒中患者CTA检查基础上联合MMP-9、TIMP-1水平检测。

Imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 may contribute to hemorrhage in cerebellar arteriovenous malformations

In this study, we determined the expression levels of matrix metalloproteinase-2 and -9 and matrix metalloproteinase tissue inhibitor-1 and -2 in brain tissues and blood plasma of patients undergoing surgery for cerebellar arteriovenous malformations or primary epilepsy （control group）. Immunohistochemistry and enzyme-linked immunosorbent assay revealed that the expression of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with cerebellar arteriovenous malformations than in patients with primary epilepsy. The ratio of matrix metalloproteinase-9 to matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with hemorrhagic cerebellar arteriovenous malformations compared with those with non-hemorrhagic malformations. Matrix metalloproteinase-2 and matrix metalloproteinase tissue inhibitor-2 levels were not significantly changed. These findings indicate that an imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-I, resulting in a relative overabundance of matrix metalloproteinase-9, might be the underlying mechanism of hemorrhage of cerebellar arteriovenous malformations.

慢性牙髓炎患者龈沟液IL-6、MMP-8、TIMP-1水平及其与牙髓活力的关系

目的 检测慢性牙髓炎患者龈沟液白介素-6 (IL-6)、基质金属蛋白酶-8 (MMP-8)、基质金属蛋白酶抑制剂-1(TIMP-1)水平,并分析其与患者牙髓活力的关系。方法 选取106例慢性牙龈炎患者(观察组)和106例健康志愿者(对照组)。取龈沟液测定IL-6、MMP-8、TIMP-1水平,比较两组差异;比较观察组不同临床特征患者龈沟液IL-6、MMP-8、TIMP-1水平。牙髓活力电测仪测定牙髓活力,比较不同牙髓活力患者龈沟液IL-6、MMP-8、TIMP-1水平,Pearson法分析观察组牙髓电活力(EPT)值与龈沟液IL-6、MMP-8、TIMP-1水平的相关性。结果 观察组龈沟液IL-6、MMP-8均高于对照组[(61.28±8.11) ng/L vs.(38.15±7.04) ng/L、(33.04±6.02) ng/mL vs.(20.05±4.18) ng/mL](P<0.05),TIMP-1水平低于对照组[(1.35±0.30) ng/mL vs.(2.04±0.41) ng/mL](P<0.05);观察组病程≥12个月、合并糖尿病患者龈沟液IL-6、MMP-8水平均高于病程<12个月、未合并糖尿病患者(P<0.05),TIMP-1水平均低于病程<12个月、未合并糖尿病患者(P<0.05);中度、重度疼痛患者龈沟液IL-6、MMP-8水平均高于轻度疼痛(P<0.05),且重度疼痛均高于中度疼痛(P<0.05),而TIMP-1水平变化趋势正相反;牙髓活力下降、无活力患者龈沟液IL-6、MMP-8水平均高于活力正常(P<0.05),且牙髓无活力均高于活力下降(P<0.05),而TIMP-1水平变化趋势正相反;观察组患牙EPT与龈沟液IL-6、MMP-8水平均呈正相关(r=0.715、0.689, P<0.05),与TIMP-1水平呈负相关(r=-0.673, P<0.05)。结论 慢性牙龈炎患者龈沟液IL-6、MMP-8水平均升高,TIMP-1水平下降,且与病程、疼痛程度、合并糖尿病、牙髓活力均有关。

血清CCL18、TIMP-1、Apelin表达与膝骨关节炎严重程度的相关性

目的:探讨血清CC趋化因子配体18(CC-chemokine ligand 18,CCL18)、基质金属蛋白酶抑制因子-1(Tissue inhibitor of metalloproteinase-1,TIMP-1)、APJ内源性配体(Apelin)表达与膝骨关节炎严重程度的相关性。方法:选取2021年10月至2022年10月我院接收的膝骨关节炎患者74例和体检健康人员100例,采用酶联免疫吸附法测定血清CCL18、TIMP-1、Apelin水平,采用Kellgren Lawrence(KL)分级评估膝骨关节炎严重程度,分析血清CCL18、TIMP-1、Apelin与膝骨关节炎严重程度的相关性。结果:与对照组相比,研究组KL-2级、KL-3级、KL-4级患者CCL18、Apelin水平升高,TIMP-1水平降低(P<0.05),且CCL18、Apelin、TIMP-1与WOMAC评分存在线性关联。CCL18、TIMP-1、Apelin是影响膝骨关节炎患者病情程度的危险因素(P<0.05)。结论:膝骨关节炎K-L分级与血清CCL18、TIMP-1、Apelin表达状态相关,可作为临床膝骨关节炎早期诊断及评估疾病进展的重要指标。

益心舒片辅助治疗心律失常的疗效及患者心功能、血清NF-κB、TIMP-1水平变化观察

目的探讨益心舒片辅助治疗心律失常的临床疗效。方法将2020年7月至2021年7月该院收治的心律失常患者106例纳入研究,通过抽签法将入选患者随机分为观察组和对照组各53例。对照组患者给予常规西医治疗,观察组在对照组治疗方案的基础上采用益心舒片辅助治疗,比较两组患者的临床疗效、主要证候积分、心功能指标、血清生化指标及不良反应发生情况。结果观察组总有效率为92.45%,对照组为75.47%,两组间比较差异有统计学意义(P<0.05)。治疗后,两组主要证候积分均较治疗前显著降低(P<0.05),两组间比较差异有统计学意义(P<0.05);两组左心室射血分数和6分钟步行距离均较治疗前增加(P<0.05),左心室收缩末期内径和左心室舒张末期内径均较治疗前减小(P<0.05),两组间上述4项指标比较差异均有统计学意义(P<0.05);两组核转录因子Kappa B、基质金属蛋白酶9和肿瘤坏死因子α水平均较治疗前显著降低(P<0.05),基质金属蛋白酶抑制因子-1水平较治疗前显著升高(P<0.05),两组间上述3项指标比较差异均有统计学意义(P<0.05)。治疗期间,观察组不良反应总发生率为5.66%,对照组为13.21%,两组比较差异无统计学意义(P>0.05)。结论益心舒片辅助治疗心律失常疗效显著,可减轻患者临床症状、炎症反应和心肌受损情况,进而提高患者心功能,延缓病情进展,安全可靠,值得临床推广应用。

安罗替尼联合PD-1抑制剂治疗晚期非小细胞肺癌患者的近期临床疗效及对血清VEGF、MMP-2水平的影响分析

目的分析安罗替尼联合程序性死亡受体1(PD-1)抑制剂治疗晚期非小细胞肺癌患者的近期临床疗效及对血清血管内皮生长因子(VEGF)、基质金属蛋白酶-2(MMP-2)水平的影响。方法选择2018年2月至2022年2月成都市第三人民医院收治的110例ⅢB~Ⅳ期非小细胞肺癌患者的临床资料,根据治疗方法不同将其分为联合治疗组(接受安罗替尼联合PD-1抑制剂治疗)和抗PD-1治疗组(接受PD-1抑制剂治疗),每组55例。两组均以21 d为一个治疗周期,每个治疗周期后停药7 d,共治疗3个周期。比较两组治疗前、治疗后1周、治疗后1个月、治疗后3个月的血清VEGF、MMP-2水平,以及疗程结束时的临床疗效。结果在接受治疗后,两组血清VEGF、MMP-2水平均呈下降趋势(P<0.05),且在治疗后1周、1个月、3个月,联合治疗组水平均较抗PD-1治疗组更低,差异有统计学意义(P<0.05)。联合治疗组的客观缓解率(ORR)、疾病控制率(DCR)均显著高于抗PD-1治疗组,差异有统计学意义(45.45%vs 23.64%,90.91%vs 76.36%;P<0.05)。两组总不良反应发生率比较差异无统计学意义(70.91%vs 78.18%;P>0.05)。结论安罗替尼联合PD-1抑制剂对晚期非小细胞肺癌患者疗效显著,能降低血清VEGF、MMP-2水平,且安全性较高。

EPO、IL-1β、MMP-9/TIMP-1与烧伤患者瘢痕评分、创面愈合时间关系及对创面愈合质量的预测价值

目的:探讨促红细胞生成素(Erythropoietin,EPO)、白介素-1β(Interleukin-1β,IL-1β)、基质金属蛋白酶-9/基质金属蛋白酶抑制剂-1(Matrix metalloproteinase-9/Tissue inhibitor of metalloproteinase-1,MMP-9/TIMP-1)与烧伤患者瘢痕评分、创面愈合时间关系及对创面愈合质量的预测价值。方法:选取2018年5月-2021年1月笔者科室收治的113例深Ⅱ度烧伤患者,采用削痂植皮联合外用重组人粒细胞-巨噬细胞刺激因子治疗,根据创面愈合质量分为良好组(n=88)、不良组(n=25),比较两组基线资料及治疗前、治疗5 d、10 d后EPO、IL-1β、MMP-9/TIMP-1,应用Pearson分析治疗5 d、10 d后EPO、IL-1β、MMP-9/TIMP-1与温哥华瘢痕量表(Vancouver scar scale,VSS)、创面愈合时间关系,采用多因素Logistic回归方程分析创面愈合质量的相关影响因素,采用受试者工作特征曲线(Receiver operating characteristic,ROC)及ROC下面积(Area under the curve,AUC)分析治疗5 d、10 d后EPO、IL-1β、MMP-9/TIMP-1,预测创面愈合质量价值。结果:不良组创面愈合时间、VSS评分数值均高于良好组(P<0.05);不良组治疗5 d、10 d后EPO低于良好组,IL-1β、MMP-9/TIMP-1高于良好组,差异均有统计学意义(P<0.05);治疗5 d、10 d后EPO与VSS评分、创面愈合时间呈负相关(P<0.05);治疗5 d、10 d后IL-1β、MMP-9/TIMP-1与VSS评分、创面愈合时间呈正相关(P<0.05);将创面愈合时间、VSS评分控制后,治疗5 d、10 d后EPO、IL-1β、MMP-9/TIMP-1仍与创面愈合质量相关(P<0.05);治疗10 d后EPO、IL-1β、MMP-9/TIMP-1的AUC大于治疗5 d后,且EPO、IL-1β联合MMP-9/TIMP-1的AUC大于任一单一指标。结论:EPO、IL-1β、MMP-9/TIMP-1与烧伤患者瘢痕评分、创面愈合时间、创面愈合质量有关,联合检测能为临床预测创面质量提供有效参考,并有望成为促进创面愈合、提高愈合质量的一个干预靶点。