Single Value of NephroCheck� Performed at 4 Hours After Surgery Does Not Predict Acute Kidney Injury in Off?Pump Coronary Artery Bypass Surgery

Background: Quantification of urinary tissue inhibitor of metalloproteinase?2 (TIMP?2) and insulin?like growth factor binding protein (IFGBP?7), which is commercially known as NephroCheck�(NC) test have been suggested as promising tools for the early detection of acute kidney injury (AKI) after cardiac surgery involving cardio?pulmonary bypass (CPB). Objectives: The aim of the present study was to test the hypothesis that single value of postoperative NC test performed at 4 hours after surgery can predict AKI in off?pump coronary artery bypass grafting (OPCABG) surgery. Setting and Design: This prospective single?center study was conducted at the tertiary cardiac center in India from December 2017 to November 2018. Methods: Ninety adult patients of both sex undergoing elective OPCABG were included. Anesthesia was standardized to all patients. Urine samples were collected preoperatively and at 4 hours after surgery for NC test. Urine output, serum creatinine, estimated glomerular filtration rate (eGFR) were also measured. AKI staging was based on kidney disease improving global outcomes (KDIGO) guidelines. Statistical Analysis: To assess the predictability of NC test for the primary endpoint, area under the receiver operating characteristic curve (ROC), was calculated. Results: Thirteen patients developed AKI in the study cohort (14.4%) out of which 7 patients (7.8%) developed stage 2/3 AKI and the remaining stage 1 AKI. Baseline renal parameters were similar between AKI and non?AKI group. The area under curve (AUC) of NC test at 4 hours after surgery was 0.60 [95% confidence interval (CI): 0.42?0.77]. Postoperative NC test performed at 4 hours after surgery did not predict AKI in this study population (P = 0.24). There were no significant differences in duration of mechanical ventilation, length of intensive care stay and hospital stay between the two groups (P > 0.05). Conclusion: NephroCheck� test performed at 4 hours after surgery did not identify patients at risk for developing AKI following OPCABG surgery

The predictive value of TIMP-2 and IGFBP7 in delayed renal function recovery after DCD renal transplantation / 中华泌尿外科杂志

Objective:This study is to investigate the predictive value of serum levels of TIMP-2 and insulin-like growth factor-binding protein 7(IGFBP7) in patients with DCD(donation after cardiac death) kidney transplantation.Methods:A prospective research design was used to select DCD kidney transplant patients admitted to the Li Huili Hospital of Ningbo University from January 2018 to October 2020.Inclusion criteria: ①Complete data; ②There were no serious complications affecting the function of the transplanted kidney in the early postoperative period.Exclusion criteria: ①Incomplete data; ②Patients were unable or unwilling to cooperate with the study; ③Severe complications affecting the function of the transplanted kidney occurred early after the operation.The ELASE method was used to quantitatively detect the serum TIMP-2 and IGFBP7 levels at 6, 12, 24, 48, 72 hours and 7 days after renal transplantation, and monitor the serum creatinine values during the same period and 21 days after the operation. According to the occurrence of DGF, the measured values of TIMP-2 and IGFBP7 at different time points and their product's ability to predict the occurrence of DGF after kidney transplantation were analyzed. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic efficacy of TIMP-2 and IGFBP7 for DGF.Results:A total of 33 patients were enrolled, 7 patients (21.2%) in the DGF group and 26 patients (78.8%) in the non-DGF group. Between the two groups, the donor glomerular filtration rate were [98.5(15.8-132.5)ml/(min·1.73m 2) and 79.1(60.6-102.5)ml/(min·1.73m 2)], recipient gender (male/female: 3/4 cases and 10/16 cases), recipient age [48(34-56) Years old and 45(23-61) years old], the recipient's preoperative creatinine [1114.0(731.4-1293.0)μmol/L and 858.4(657.6-1051.9)μmol/L], the recipient's preoperative urea nitrogen [15.0(13.2-19.6)mmol/L and 17.3(13.6-20.9)mmol/L], receptor preoperative albumin [43.5(38.5-45.3)mmol/L and 41.2(37.5-46.1) mmol/L], recipient dialysis method [hemodialysis/peritoneal dialysis: 3/4 cases and 9/17 cases], warm ischemia time [6(5-7) and 5(4-6) min, there was no statistically significant difference] ( P>0.05). The values of serum IGFBP7 and TIMP-2×IGFBP7 in the DGF group were higher than those in the non-DGF group at all time points ( F=15.753, P=0.040; F=13.000, P=0.024), while serum TIMP-2 was not significant between the two groups difference ( F=1.157, P=0.075). For the diagnostic value of DGF, the AUC of serum IGFBP7 at 48 h after surgery was 0.863 (95% CI 0.696-1.000, P=0.004). When 5.97 ng/ml was used as the cut-off value, the sensitivity was 85.7% and the specificity was 80.8 %. The AUC of TIMP-2×IGFBP7 at 48 hours after surgery was 0.819 (95% CI 0.641-0.996, P=0.011). When 62.06(ng/ml) 2 was used as the cutoff value, the sensitivity was 71.4% and the specificity was 80.8%.There was no statistical difference in the area under the curve between the two ( P>0.05). There were differences in the dynamic trend of serum IGFBP7 and creatinine in the DGF group. Serum IGFBP7 at 7 days after surgery was positively correlated with creatinine at 21 days after surgery. Conclusion:Serum IGFBP7 and TIMP-2×IGFBP7 could predict the occurrence of DGF after DCD donor kidney surgery. The predictive value changes with time. Among them, 48h and 7d after surgery are the most valuable. However, serum TIMP-2 has not been found to have predictive value in this study.

RECK and TIMP-2 mediate inhibition of MMP-2 and MMP-9 by Annona muricata

Up-regulation of MMP-2 and MMP-9 plays a significant role in promoting cancer progression by degradingthe components of the extracellular matrix, thereby enhancing the migration of tumor cells. Although the antiproliferative and apoptotic effect of Annona muricata is well established, its effect on MMP-2 and MMP-9, amajor target in several types of cancers, has not been studied. Powdered samples of various parts of A.muricata like fruit, stem, seed, and twig extracted using aqueous methanol showed significant dose-dependentinhibition of MMP-2 and MMP-9 in a highly metastatic fibrosarcoma cell line, HT1080. Additionally, theseextracts also up-regulated the expression of several endogenous inhibitors of MMP-2 and MMP-9 likeREversion-inducing Cysteine-rich protein with Kazal motifs (RECK) and Tissue Inhibitor of Metalloproteinase-2 (TIMP-2). Furthermore, primary cells developed from tumor tissues obtained from patients notexposed to chemotherapy, also exhibited similar results. Remarkably, the inhibition of MMP-2 and MMP-9observed was tumor specific, with the A. muricata fruit extract showing only 2% inhibition in cells obtainedfrom normal tissues, when compared to 60% inhibition observed in cells obtained from tumor samples. Thepresent study elucidates a novel mechanism by which A. muricata extracts selectively exhibit their anti-canceractivity in tumor cells by down-regulating MMP-2 and MMP-9 that are important biomarkers in cancer.

miR-106a regulates the proliferation of ovarian granulosa cells by targeting TIMP-2 / 中国临床药理学与治疗学

AIM: To investigate the regulation function of miR-106a on the proliferation of human ovarian granulosa cells, and to explore its possible target.METHODS: The expression of miR-106a in granulosa cells was regulated by cell transfection, and its expression level was detected by RT-PCR. The MTT assay was used to detect the cell proliferation activities of cells. Bioinformatics methods were used to predicted the possible target genes of miR-106a, which were verified them by double-luciferase assay. The expression of target protein was detected by Western blot. RESULTS:The expression of miR-106a in KGN cells was significantly higher than that of normal ovarian epithelial cell (IOSE80), the difference was statistically significant (P<0.05). The proliferation activity of KGN cells was significantly decreased after inhibiting the expression of miR-106a (P<0.05). The results of dual luciferase assay showed that miR-106a could directly target TIMP-2 gene. Western blot results showed that the expression level of TIMP-2 protein was significantly decreased after overexpression of miR-106a (P<0.05). CONCLUSION: miR-106a can promote the proliferation of KGN cell; The mechanism is related to the targeted reduction of TIMP-2 expression level.

Effect of baicalin on expression of fibrogenic factors TGF-β1, mmp2 and timp2 in tissue of mice with pulmonary fibrosis / 中国中药杂志

To investigate the effect of baicalin extracted from Qinbai Qingfei Concentrated Pills on the expressions of TGF-β1, mmp2 and timp2 in mice with pulmonary fibrosis induced by bleomycin. The Biacore technique was used to detect the specific binding between Qinbai Qingfei Concentrated Pills and TGF-β1, and the affinity components were enriched, regenerated and recovered by Biacore fishing. Then ultra-performance liquid chromatography and quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS) were used to determine whether the monomer was baicalin. Biacore was used to verify the affinity kinetics of baicalin, which was validated by pharmacodynamics in vivo. Totally 30 BALB/C mice were randomly divided into three groups: baicalin group, blank group and model group. The blank group was given sodium chloride injection(0.08 mL·kg~(-1)), while the model group and the baicalin group were injected with 4 mg·kg~(-1) bleomycin. The localization of TGF-β1, mmp2 and timp2 protein in the cells and the mRNA expressions of TGF-β1, mmp2 and timp2 were detected by RT-PCR 14 days later. The results of Biacore affinity analysis showed that the peak of binding response between Qinbai Qingfei Concentrated Pills and TGF-β1 protein reached 1 524.0 RU, with specific binding. The affinity constant K_D of baicalin and TGF-β1 was 1.620 06 μmol·L~(-1), which was determined by SPR kinetic analysis, suggesting a stable binding between baicalin and TGF-β1, which verified the results of angulation. The results of immunohistochemistry showed that the deposition of cellulose in baicalin group was significantly less than that in model group, the mRNA expressions of TGF-β1, mmp2 and timp2 were decreased in baicalin solution compared with the model group. Baicalin combined with TGF-β1 could inhibit the expressions of mmp2 and timp2 and delay the progress of pulmonary fibrosis.

Clinical Efficacy of Modified Qingqi Huatan Wan in Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease and Its Effect on Inflammatory Reaction, Airway Remodeling and Thrombokinesis / 中国实验方剂学杂志

Objective:To explore the clinical efficacy of Modified Qingqi Huatan Wan in treatment of acute exacerbation of chronic obstructive pulmonary disease and its effect on inflammatory reaction, airway remodeling and thrombokinesis. Method:A total of 80 patients of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) were randomly divided into control group (40 cases) and therapy group (40 cases) by random number table. The control group was treated with conventional therapy. In addition to the therapy for the control group, the patients in therapy group also received modified Qingqi Huatan Wan. The treatment course was 14 days for both groups. Scores of traditional Chinese medicine(TCM) syndrome, chronic obstructive pulmonary disease and asthma physiology Score (CAPS), and chronic obstructive pulmonary disease patients self-assessment test questionnaire (CAT) were compared. The secondary indicators were pulmonary function, arterial blood gas analysis, and blood rheology indexes. In addition, the levels of serum nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), interleukin-8 (IL-8), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), transforming growth factor-beta1 (TGF-β1) and plasma tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von-willebrand factor (v-WF), clinical efficacy and safety were evaluated. Result:The total clinical effective rate was 94.74% in therapy group,which was higher than 78.38% in control group (χ2=4.341,P2, serum NF-κB, IL-6, IL-8, MMP-2, TIMP-2, TGF-β1 and plasma PAI-1, v-WF in therapy group were lower than those in control group(P2, PaO2, FEV1, FEV1%, FEV1/FVC in therapy group were higher than those in control group(PPConclusion:Modified Qingqi Huatan Wan can control the symptoms safely, alleviate CAPS and lung function, effectively reduce the inflammatory response and inhibit the formation of airway remodeling and thrombosis, and its mechanism may be protect the lung tissue by reducing the level of inflammatory cytokines, regulating the balance of MMP-2/TIMP-2 and t-PA/PAI-1 and improving extracellular matrix and vascular endothelial function.

Effect of modified Buzhong Yiqi decoction combined with pelvic floor muscle exercise-biofeedback-electrical stimulation on early stage postpartum pelvic floor dysfunction / 中国中药杂志

To investigate the curative effect of modified Buzhong Yiqi decoction combined with pelvic floor muscle exercise-biofeedback-electrostimulation on early postpartum pelvic floor dysfunction disease (PFD) and its effect on the expression of transforming growth factor (TGF-β1), matrix metalloprotein (MMP-2), and tissue inhibitor of metalloproteinase (TIMP-2). A total of 186 PFD patients admitted to our hospital from March 2014 to December 2016 were selected in the study and were randomly divided into test group (=93) and control group (=93). The control group received pelvic floor muscle exercises-biofeedback-electrostimulation, while the test group was additionally treated with modified Buzhong Yiqi decoction based on the treatment in control group. Then the clinical efficacy was compared between two groups. The results showed that vaginal contractile electromyography (EMG), duration of vaginal constriction, dynamic vaginal pressure and pelvic floor myoelectric activity in the test group at 1, 3 and 6 months after treatment were significantly higher than those before treatment and the control group (<0.05). The effective rate for urinary incontinence was 97.14% in test group, significantly higher than 75.68% in the control group (<0.05). The effective rate for improvement of sexual life quality was 96.43% in test group, significantly higher than 74.07% in control group (<0.05). 1, 3 and 6 months after treatment, the uterine prolapse, posterior wall prolapse and anterior wall prolapse grade in test group was slightly lower than that in the control group, but the difference was not statistically significant. After treatment, the levels of TGF-β1 and TIMP-2 in the test group were higher than those in the control group, while the levels of MMP-2 were lower than those in the control group (<0.05). The results showed that modified Buzhong Yiqi decoction combined with pelvic floor muscle exercise-biofeedback-electrostimulation can effectively relieve the clinical symptoms, promote the body recovery and improve the quality of sexual life in PFD patients, with remarkable advantages, so it is worthy of popularizing.

Expression of MMP-2 and TIMP-2 in laser-induced choroidal neovascularization in guinea pigs model with form-deprivation high myopia / 复旦学报（医学版）

Objective To establish the high myopic choroidal neovascularization (CNV) in guinea pigs and to investigate the role of (matrix metalloproteinase-2,MMP-2) and tissue inhibitor-2 of metalloproteinase (TIMP-2) in high myopic CNV.Methods Seventy-two 2-week-old guinea pigs were randomized into control group (n =36) and high myopia group (n =36).Right eyes were indued form deprivation high myopia for 6 weeks.Thirty guinea pigs were randomly selected in each group,and CNV were induced in the right eyes br the 532 nm laser.MMP-2 and TIMP-2 expressions were investigated by immunohistochemistry pre-laser and 7,14,21,28,35 days after laser induction,respectively,while MMP-2 and TIMP-2 relative expression levels in retinal pigment epithelium (RPE)-choroid-sclera complex were detected by real-time PCR.Integral opitical density (IODs) of positive expression and mRNA relative expression levels of these factors were performed by statistical analyses.Results The expressions of MMP-2 and TIMP-2 were up-regulated in the two groups after laser photocoagulation through immunohistochemistry and real-time PCR examinations.Expression of MMP-2 peaked at 21 d and TIMP-2 at 28 d,respectively.IODs of positive expression and mRNA relative expression levels of MMP-2 were higher in high myopia group than those in control group at each inspective time point,and the differences were statistically significant (P ＜ 0.05).TIMP-2 expression was significantly reduced in high myopia group compared with control group before laser photocoagulation (P＜0,05),while there was no significant difference between the two groups at each time point after laser photocoagulation.Conclusions MMP-2 and TIMP-2 were closely related to the formation of high-myopic CNV.Balance disorders of MMP-2 and TIMP-2 might participate in the occurrence and development of high-myopic CNV.

Effects of HPS on Myocardial Fibrosis and Expression of MMP-2/TIMP-2 in Model Mice of Diabetic Cardiomyopathy / 中国中医药信息杂志

Objective To observe the effects of hedysari polysaccharide (HPS) on myocardial fibrosis and the expression of MMP-2/TIMP-2 in model mice of diabetic cardiomyopathy; To discuss the mechanism of action of prevention and treatment of myocardial fibrosis in diabetes.Methods Sixty mice were randomly divided into model group, rosiglitazone group and HPS high-, mediume- and low-dose groups. The normal group was 12 non-transgenic male BKS.Cg-Dock7m+/+Leprdb/JNjumice with the same age. Each group was given relevant medicine for gavage, for 8 weeks. Blood glucose of mice before and after medication 2, 4, 6, and 8 weeks was detected. The levels of MMP-2, MMP-2 and MMP-9 in myocardium were measured by Masson staining. The protein expressions of MMP-2 and TIMP-1 in myocardium were detected by Western blot.Results Compared with the model group, the blood glucose of HPS (high- and medium dose) groups and rosiglitazone group decreased significantly. Masson staining showed that the green fibers in the model group significantly increased and rosiglitazone group and HPS high-dose group decreased compared with the model group. Western blot showed that the expressions of MMP-2 in model group and MMP-2/TIMP-2 ratio were declined significantly, while the expression of MMP-2 was increased and TIMP-2 was decreased significantly, and the ratio of MMP-2/TIMP-2 increased in rosiglitazone group and HPS high- and medium-dose group.Conclusion HPS may reduce the degree of myocardial fibrosis in model mice with diabetic cardiomyopathy. The therapeutic effect of HPS may be to relieve myocardial fibrosis in model mice by increasing the ratio of MMP-2/TIMP-2.

Expression of TIMP-2 in HPV-16 infected oral squamous cell carcinoma in patients in Iraq

Aim: To determine the expression of tissue inhibitors of metalloproteinases (TIMP-2) in oralsquamous cell carcinoma (OSCC) and the difference in its expression level between positiveand negative HPV-16 (human papilloma virus- 16) OSCC patients. Methods: This study wasconducted on 33 biopsies obtained from patients with OSCC and 10 normal oral mucosa ascontrols. In situ hybridization (ISH) was used to investigate the presence of HPV-16, whileimmunohistochemistry (IHC) was used to estimate the expression level of TIMP-2. Results: TheTIMP-2 was expressed in 27 (81.8%) of OSCC sections with no significant difference betweenits expression level in HPV-16 positive and HPV-16 negative OSCC cases (p=0.058). TIMP-2was found to be highly expressed in OSCC sections, and the presence of HPV was not relatedto its overexpression. Conclusions: The percentage of samples that appeared to accommodatedetectable HPV-16 was high, but no significant difference was observed in relation to TIMP-2expression level. Future studies with a larger number of patients are highly recommended toaddress the possible association between TIMp-2 and OSCC positive HPV-16.

Effect of low intensity pulsed ultrasound on expression of TIMP-2 in serum and expression of mmp-13 in articular cartilage of rabbits with knee osteoarthritis

Objective: To study the effect of low intensity pulsed ultrasound (LIPUS) on the expression of tissue inhibitor of metalloproteinase-2 (TIMP-2) in the serum and expression of matrix metallopeptidase 13 (MMP-13) in the articular cartilage cells of rabbits with knee osteoarthritis (OA). Methods: Inner patellar ligament defect method was used to establish the model of knee OA. Four weeks after the modeling, the arterial blood was drawn from the ear of each rabbit, while ELISA was employed to detect the expression of TIMP-2 in the serum. The chondrocytes were separated from animals in each group and then cultured in vitro. All rabbits were divided into control group, OA model group and OA + LIPUS group. Cells in the control and OA groups were not treated, while cells in the OA + LIPUS group were treated with LIPUS (40 mW/cm

Effect of low intensity pulsed ultrasound on expression of TIMP-2 in serum and expression of mmp-13 in articular cartilage of rabbits with knee osteoarthritis

OBJECTIVE@#To study the effect of low intensity pulsed ultrasound (LIPUS) on the expression of tissue inhibitor of metalloproteinase-2 (TIMP-2) in the serum and expression of matrix metallopeptidase 13 (MMP-13) in the articular cartilage cells of rabbits with knee osteoarthritis (OA).@*METHODS@#Inner patellar ligament defect method was used to establish the model of knee OA. Four weeks after the modeling, the arterial blood was drawn from the ear of each rabbit, while ELISA was employed to detect the expression of TIMP-2 in the serum. The chondrocytes were separated from animals in each group and then cultured in vitro. All rabbits were divided into control group, OA model group and OA + LIPUS group. Cells in the control and OA groups were not treated, while cells in the OA + LIPUS group were treated with LIPUS (40 mW/cm(2), 1 time/day). Cells were collected 7 d later and the RNA and total protein were extracted respectively. Real-time PCR and Western blotting were employed to analyze the expression of MMP-13 in chondrocytes at the mRNA and protein level, respectively.@*RESULTS@#The success rate of establishment of OA model was 83%. The results of ELISA showed that the content of TIMP-2 in the serum of animals with OA was 22.3%, lower than the one in the control group (P < 0.05). Compared with the normal control group, the expression of TIMP-2 in the OA model group was significantly increased, while the expression of MMP-13 was significantly increased (P < 0.05). After the stimulation of LIPUS, the expression of TIMP-2 and MMP-13 was close to the one in the normal control group.@*CONCLUSIONS@#The inner patellar ligament defect method is a mature method to establish the rabbit OA model, with high success rate. The expression of serum TIMP-2 in the OA model group is significantly decreased. LIPUS can up-regulate TIMP-2 and down-regulate MMP-13.

Correlation of MMP-2 and TIMP-2 with Mesangial Proliferative Glomerulo-nephritis and Its Research Progress in Traditional Chinese Medicine / 浙江中医药大学学报

Objective] To explore both the correlation of matrix metal oproteinase and the imbalance of its tissue inhibitors-MMP-2 and TIMP-2 with glomerulosclerosis and its research progress in traditional Chinese medicine. [Methods] We generalized the research progress in traditional Chinese medicine from such aspects as the biological properties of MMP-2 and TMIP-2 and their mechanisms, their relationship with mesangial proliferative glomerulonephritis and effects of traditional Chinese medicine on their expression by searching the relevant literatures. [Results] Expressions of MMP-2 and TIMP-2 vary in different pathological stages(hyperplasia and sclerosis stage here) of glomerulonephritis, and traditional Chinese herbs could adjust their expressions in different stages. Traditional Chinese herbs can inhibit the development of glomerulosclerosis. [Conclusion] Applying traditional Chinese medicine in the treatment of mesangialproliferative glomerulonephritis could provide the base for further development of TCM as wel as a new choice for treating mesangialproliferative glomerulonephritis.

Influence of irbesartan on left ventricular remodeling and MMP-2, TIMP-2 in patients with hypertension diseases / 中国基层医药

Objective To explore the clinical significance and influence of left ventricular remodeling and serum MMP-2,TIMP-2 levels after treated by irbesartan on hypertension patients.Methods The control group was only treated with conventional therapy,and the treatment group was given irbesartan besides conventional therapy.To observe the changes of LVMI,RWT and serum MMP-2,TIMP-2 levels before and after treated in the two groups.Results The hypertension group LVMI,RWT and serum MMP-2,TIMP-2,MMP-2/TIMP-2 levels were higher than the healthy control group (P ＜ 0.01).The levels of LVMI,RWT and serum MMP-2,TIMP-2,MMP-2/TIMP-2 after irbesartan treatment were significantly lower than before treatment in the treatment group(all P ＜ 0.01),and the levels of LVMI,RWT and serum MMP-2,TIMP-2,MMP-2/TIMP-2 had statistically significant differences between the two groups(all P ＜ 0.05).The serum levels of MMP-2,T IMP-2,MMP-2/TIMP-2 were positively correlated with LVMI,RWT in patients with hypertension.Conclusion Irbesartan can reverse hypertension myocardial fibrosis so as to improve left ventricular remodeling,the mechanism may be through inhibiting myocardial remodeling by reducing the expressions of MMP-2,TIMP-2 and down-regulating the MMP-2/TIMP-2 ratio.

Clinical observation on the treatment of breast cancer with traditional Chinese and western medicine / 国际中医中药杂志

Objective To explore the influence of breast cancer treated with chemo-therapy and Shengxue decoction.Methods 91 Cases of breast cancer were randomly recurited into two groups:The western medicine treatment group (40 patients) was given anastrozole tablets and chemo-therapy; The Chinese and western medicine treatment group (51 patients) was given chemo-therapy and Shengxue decoction.Results The total effective rate of was 82％ and 53％ in the Chinese and western medicine treatment group and western medicine treatment group respectively,the difference was statistically significant (x2=19.74,P＜0.05).The peripheral blood's CEA and MMP-2 mRNA expression of western medicine treatment were [ (7.50 ±4.32)ng/ml、(116.32±67.40)ng/ml respectively],higher than the Chinese and western medicine treatment group [ (7.20 ± 3.22) ng/ml、(105.08 ± 37.82) ng/ml,respectively,P＜ 0.05 ],but the TIMP-2/MMP-2 (26.65 ±19.75) was significantly lower compared with the Chinese and western medicine treatment group [ (39.48±21.21) (P＜0.05) ].Conclusion The combination of traditional Chinese and western medicine was effective in treatment of breast cancer and well worth for popularization.

Genome-wide Association Study Identified TIMP2 Genetic Variant with Susceptibility to Osteoarthritis

Osteoarthritis (OA) is the most common degenerative joint disorder in the elderly population. To identify OA-associated genetic variants and candidate genes, we conducted a genome-wide association study (GWAS). A total 3,793 samples (476 cases: wrist + knee and 3317 controls) from a community-based epidemiological study were genotyped using the Affymetrix SNP 5.0. An intronic SNP (rs4789934) in the TIMP2 (tissue inhibitor of metalloproteinase-2) showed the most significance with OA (odd ratio [OR] = 2.06, 95% confidence interval [CI] = 1.52-2.81, p = 4.01 x 10(-6)). Furthermore, a polymorphism (rs1352677) in the NKAIN2 (Na+/K+ transporting ATPase interacting 2) was suggestively associated with OA (OR = 1.43, CI = 1.22-1.66, p = 7.01 x 10(-6)). The present study provides new insights into the identification of genetic predisposing factors for OA.

Biomarkers for identifying the early phases of osteoarthritis secondary to medial patellar luxation in dogs

The levels of tartrate resistant acid phosphatase (TRAP), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in synovial fluid (SF) and serum in cases of canine osteoarthritis (OA) were measured. OA was induced by a surgically-created medial patellar luxation in the left stifle of 24 dogs. SF and blood samples were collected at 1.5- and 3-month intervals, respectively. Every 3 months, one dog was euthanatized to collect tissue samples from both stifles. TRAP levels in SF and serum were measured using a spectrophotometer, and TRAP-positive cells in joint tissues were identified by enzyme histochemistry. MMP-2 and TIMP-2 in SF and serum were detected by Western blotting and ELISA, respectively. TRAP in SF from the stifles and serum was significantly increased (p < 0.05) after 3 months. TIMP-2 in SF and serum was significantly decreased (p < 0.05), whereas MMP-2 in SF was significantly increased (p < 0.05) during the progression of OA. Histochemistry revealed an increased number of TRAP-positive cells in tissues from OA-affected joints. Assays measuring TRAP, MMP-2, and TIMP-2 in SF and serum, and methods that detect increased numbers of TRAP-positive cells in the joint tissues can play an important role in identifying the early phases of degenerative changes in canine joint components.

Relationship between invasion and changes of mRNA epression of MMP-2, TIMP-2 and CD147 in human pituitary adenoma / 中华内分泌外科杂志

Objective To investigate the relationship between tumor invasion and changes of mRNA expression of MMP-2, TIMP-2 and CD147 in human pituitary adenoma. Methods 60 patients with pituitary adenoma were devided into two groups, invasive and non-invasive group, by MRI. The expression level of MMP-2,TIMP-2 and CD147 in the samples of pituitary adenoma was measured by semiquantitative reverse transcriptasepolymerase chain reaction (RT-PCR). Pearson analysis was used to reveal the correlation between the expression of each marker. Results The mRNA expression level of MMP-2 and CD147 was significantly higher in invasive pituitary adenoma group than that in non-invasive group (P ＜ 0. 01 ) while the mRNA expression level of TIMP-2was lower in invasive pituitary adenoma group than that in non-invasive group (P ＜0.01 ). According to Pearson analysis, the mRNA expression of MMP-2 was positively correlated with CD147 in invasive pituitary adenoma (r=0. 69, P ＜ 0. 05 ), and M MP-2 was negatively correlated with TIMP-2 in non-invasive pituitary adenoma (r =-0.68, P ＜ 0.05 ). Conclusions The invasion of human pituitary adenoma are closely related to the low expression level of TIMP-2 as well as the high expression level of MMP-2 and CD147. MMP-2, TIMP-2 and CD147 can be used as indicators of tumor invasion of human pituitary adenoma.

Expression of COX-2, MMP-2 and TIMP-2 in human breast cancer / 中国综合临床

Objective To investigate the expression of COX-2,MMP-2 and TIMP-2 ,the pathological fea-tures ,and their relationship in breast cancer. Methods The expressions of COX-2 ,MMP-2 and TIMP-2 were deter-mined by S-P immunohistochemical method on tissue chips,which containing 127 cases of breast carcinoma. Results The positive rates of COX-2,MMP-2 and TIMP-2 protein were 81.1 (103/127)% ,96.9(123/127)% and 60.6 (77/127) % respectively;The expression of COX-2 was positively related to auxiliary lymph node metastasis and TNM staging (P<0.01 and P<0.05, respectively), and inversely related to PR expression (P<0.05). Further-more,the expression of COX-2 was positively correlated with MMP-2 (r=0. 290 ,P<0.01). Conclusions The ex-pression of COX-2 might be closely related to the invasion and metastasis of breast cancer and has a close relation-ship with MMP-2. The levels of MMP-2 might be partly regulated by COX-2.

Expression of EMMPRIN, MMPs and TIMP2 in retinoblastoma and normal retinal tissue / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the expression of EMMPRIN, MMP1, MMP9 and TIMP2 in retinoblastoma (RB) and normal retinal tissues and their clinicopathological significance and interrelationship.METHODS: Envision immunohistochemistry stainings of EMMPRIN, MMP1, MMP9 and TIMP2 were performed in 30 enucleated eyeballs with retinoblastoma and 15 specimens of normal retina tissue, which had been routinely imbedded with paraffin.RESULTS: Positive rate of EMMPRIN, MMP1, MMP9 expression was higher in RB tissue than in normal control (P<0.01), while TIMP2 expression was lower in RB than in normal retinal tissue (P<0.01). Samples from RB cases of clinical stage Ⅰ, differentiated type, and life span≥2 years had lower positive rate in expression of EMMPRIN, MMP1, MMP9 than those from RB cases of clinical stage Ⅲ, undifferentiated type, and life span<2 years (P<0.05 or P<0.01), while samples from RB cases of differentiated type, optic nerve unaffected, and life span≥2 years had markedly higher positive rate in expression of TIMP2 than those from RB cases of undifferentiated type, optic nerve involved and life span<2 years (P<0.05 or P<0.01). In RB tissues, EMMPRIN, MMP1, MMP9 expressions were highly consistent (P<0.05), whereas TIMP2 expression is highly inconsistent with EMMPRIN, MMP1, MMP9 expression levels (P<0.05).CONCLUSION: The expression level of EMMPRIN, MMP1, MMP9 and TIMP2 may be an important marker of RB progression, invasion and prognosis. There exist internally mutual regulation relations among them.