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Objective@#To investigate the correlation between campus bullying and suicidal tendency symptoms comorbidity with addictive behavior among middle and high school students in Hainan Province, so as to provide a theoretical basis for health education and behavioral intervention in schools.@*Methods@#In July 2023, an anonymous questionnaire survey was conducted among 6 654 middle and high school students in Hainan Province, selected by probability proportional sampling and stratified cluster random sampling method. Campus bullying, suicidal tendency and addictive behavior were determined according to the relevant items in the questionnaire on health related behaviors of Chinese students health status and influencing factors questionnaire, and self designed questionnaire. The co occurrence of campus bullying and suicidal tendency among students was analyzed. The binary Logistic regression method was used to analyze the correlation between the co occurrence of campus bullying and suicidal tendency and the addictive behavior of middle school students.@*Results@#The report rate of campus bullying among middle and high school students in Hainan Province was 28.48%, the suicidal tendency was 15.25%, and the co occurrence of campus bullying and suicidal tendency was 8.00%. The results of Logistic regression analysis showed that middle school students and left behind students were prone to campus bullying and suicide tendency ( OR =1.55, 1.52, P <0.05), while Internet addiction, gambling and current smoking showed significant positive correlation with comorbidity of campus bullying and suicide tendency ( OR =3.14, 2.18, 2.07, P < 0.05 ).@*Conclusions@#Middle and high school students with addictive behavior have a higher possibility of comorbidity of campus bullying and suicidal tendency. The comprehensive intervention of addictive behavior can reduce the incidence of co occurrence of campus bullying and suicidal tendency, so as to improve health and wellbeing of middle school students.
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Objective:To explore the correlation between blood glucose level and parental education level in children with type 1 diabetes mellitus (T1DM) based on mobile health APP.Methods:The data of T1DM children enrolled in China′s T1DM registration management program and registered to use TangTangquan ? were collected, as well as the blood glucose monitoring information uploaded quarterly after registration. Children were divided into low education group (middle school or below) and high education group (junior college or above) according to their parents′ education level. Blood glucose levels were compared between the two groups at different time points. Spearman correlation analysis and multivariate logistic regression analysis were used to evaluate the correlation between blood glucose level and parents′ education level in children with T1DM. Results:A total of 2 263 eligible children with T1DM were included and 1 246 were female (55.1%). The median age was 7.9(4.4, 11.4)years and T1DM duration was 0.07(0.02, 0.46)years. Among them, 1 513 cases were in the low-education group while 750 cases were in the high-education group. Within three years after registration, the glucose levels of each interval in the low-education group were increasing gradually (all P<0.05 except post-breakfast glucose). The glucose levels of each interval in the high-education group in the third year were lower than those in the low-education group (all P<0.05 except nocturnal glucose). The result of multivariate logistic regression analysis showed that after the adjustment of factors including T1DM duration and treatment, parental educational levels were still the separate related factors of premeal glucose, bedtime glucose and nocturnal glucose (premeal glucose: OR=0.385, 95% CI: 0.164-0.874, P=0.025; bedtime glucose: OR=0.444, 95% CI: 0.204-0.949, P=0.038; nocturnal glucose: OR=0.226, 95% CI: 0.582-0.747, P=0.020). Conclusions:The blood glucose levels of children with T1DM were negatively associated with parental educational levels. It is suggested that parental educational levels should be taken into consideration in the management of T1DM for children.
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Ischemic stroke is a common neurological disorder that can lead to neuronal death and neurological dysfunction. Microglia is the main immune cells in the central nervous system, involved in post-stroke inflammation and tissue repair. Triggering receptor expressed on myeloid cells 2 (TREM2), a receptor expressed on the surface of microglia, plays a multifaceted role in neuronal survival and nerve repair after ischemic stroke, including promoting the phagocytosis of microglia, inhibiting excessive inflammatory response, maintaining the proliferation and survival of microglia, protecting neurons from damage, and promoting the recovery of nerve function. Therefore, elucidating the immunoregulatory mechanism of TREM2 on microglia after cerebral ischemia is of great significance for exploring new therapeutic directions for ischemic stroke.
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Phagoptosis is a kind of cell death mode which has been widely concerned in recent years. Previous studies have shown that the phagocytosis of viable neurons by microglia (phagoptosis) may be involved in the pathophysiological processes of various neurological diseases, including ischemic stroke. After cerebral ischemia, microglia chemotaxis towards ischemic brain tissue, and then recognize and engulf the stressed neurons, leading to further damage or even death of neurons, thereby exacerbating cerebral ischemic injury. This article reviews the relationship between phagoptosis and cerebral ischemia, with a focus on elucidating the molecular mechanisms of phagoptosis after cerebral ischemia, in order to provide new targets and strategies for the treatment of cerebral ischemia.
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Objective To investigate the value of endoscopic carbon nanoparticles labeling technique assisted in situ resection after neoadjuvant chemoradiotherapy(nCRT)for middle and low locally advanced rectal cancer(LARC).Methods From January 2020 to January 2023,46 cases of middle or low LARC were selected for endoscopic injection of carbon nanoparticles suspension to label the lower edge of the tumor before nCRT,and laparoscopic anterior resection of the rectum was performed after nCRT.The main observations were the visualization of carbon nanoparticles marker during the operation,the length of each area(primary tumor area,tumor regression scar,distal resection margin,and regression area of lower edge of tumor)of surgical specimens and the positive rate of distal resection margins.Results The median interval between injection of carbon nanoparticles suspension and surgery was 105(77-182)d in the46 cases.Carbon nanoparticles remnants were observed on the rectal mucosal surface in all the patients after nCRT by endoscopy.During laparoscopic anterior rectal resection surgeries,carbon nanoparticles marker exposure on the surface of the rectal intrinsic fascia observed in 41 cases(89.1%),of which38 cases were judged as good exposure(the width of marker area≤1.5 cm,which assisted the operator accurately determining the distal surgical margins)and 3 cases were judged as inferior exposure(a larger range of black staining whereas in situ resection of the tumor still achievable).In another 5 cases,the carbon nanoparticles marker could not be observed and were judged as exposure failure.Intraoperative cryopathology showed that all distal resection margins were negative.Measurement of 30 surgical specimens with identifiable primary tumor area showed that the length of resected intestinal canal was 17.9(10.1-25.7)cm,the diameter of primary tumor area was(4.3±0.8)cm,the diameter of scar after tumor regression was 2.5(0.8-4.8)cm,and the length of regression of tumor lower margin was 1.0(0-2.9)cm.The length of distal resection margins in middle rectal cancer(n =17)was3.4(1.5-4.3)cm and in low rectal cancer(n =13)was1.6(0.5-2.8)cm.Conclusion Application of carbon nanoparticles labeling technology before nCRT for rectal cancer can effectively mark the lower margin of the primary tumor in a long time and assist surgeons to precisely remove the primary tumor area.
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Cancer-associated fibroblasts (CAFs) and tumor-infiltrating immune cells are the most essential components of the tumor microenvironment (TME). They communicate with each other in tumor microenvironment and play a critical role in tumorigenesis and development. CAFs are very heterogeneous and different subtypes of CAFs display different functions. At the same time, it can contribute to the regulation of the function of tumor-infiltrating immune cells and eventually result in the carcinogenesis, tumor progression, invasion, metastasis and other biological behaviors of tumors by producting various growth factors and cytokines etc. Based on the current research results at home and abroad, this paper reviews the recent research progress on the regulation of CAFs on infiltrating immune cells in tumor microenvironment. .
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Humans , Cancer-Associated Fibroblasts/metabolism , Carcinogenesis , Cell Transformation, Neoplastic/metabolism , Lung Neoplasms/metabolism , Tumor MicroenvironmentABSTRACT
Objective To evaluate the effect of blind bedside non-spiral nasointestinal tubes in critically ill patients.Methods Patients requiring bedside nasointenstinal tubes in intensive care unit of Nanjing First Hospital from February 2017 to February 2018 were enrolled in this study.The placement of nasointenstinal tubes was conducted according to the reference procedure of our department,recording operation times,operation duration,position of the tube's tip,expense and complications.Results A total of 53 patients received the bedside non-spiral nasointenstinal tubes which were conducted for 64 times.51 patients (51/53,94.4％) were successful in tube placement,45 case-times (45/64,70.3％) were successful at the first attempt,and 50 case-times (50/64,78.1％) were successful at the second attempt in accumulation.The mean time of our procedure was (13.80±6.90) minutes,the mean insertion length was (99.55±8.35) cm,and the mean expense was (244.82±45.68) Yuan.No severe complications were observed.Conclusion Blind bedside placement of non-spiral nasointestinal tubes has high success rate and many advantages as short operation time,low expense and less complications,which is a good choice for early establishment of enteral feeding pathway and early supplement of enteral nutrition in critically ill patients.
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Parthenogenetic embryonic stem cells (pESCs) derived from bi-maternal genomes do not have competency of tetraploid complementation, due to lacking of paternal imprinting genes. To make pESCs possess fully development potentials and similar pluripotency to zygote-derived ESCs, we knocked out one allelic gene of the two essential maternal imprinting genes (H19 and IG) in their differentially methylated regions (DMR) via CRISPR/Cas9 system and obtained double knock out (DKO) pESCs. Maternal pESCs had similar morphology, expression levels of pluripotent makers and in vitro neural differentiation potentials to zygotes-derived ESCs. Besides that, DKO pESCs could contribute to full-term fetuses through tetraploid complementation, proving that they held fully development potentials. Derivation of DKO pESCs provided a type of major histocompatibility complex (MHC) matched pluripotent stem cells, which would benefit research in regenerative medicine.
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Animals , Mice , Embryonic Stem Cells , Gene Knockout Techniques , Genomic Imprinting , Parthenogenesis , Pluripotent Stem Cells , Regenerative Medicine , TetraploidyABSTRACT
Objective@#To investigate the clinical effect of the combination of distal subcutaneous buried suture, to reduce local tension, and electron irradiation for the treatment of keloid.@*Methods@#From May 2014 to July 2016, nine female patients with recurrent keloid in torso were treated by above method. After eligibility was confirmed, surgery was performed to completely excise the keloid. An extensive subcutaneous segregation was made around the incision. The 4-0 PDS Ⅱ sutures were buried in the subcutaneous layer, 1.5 cm from the edges of incision, 1 cm apart from each other, and were knotted from both ends of the incision to the center. The normal skin on both sides of the incision were pulled toward the center, and completely relaxed without tension. An interrupted subcutaneous suture was made with a 4-0 Coated VICRYL absorbable suture, and a continuous intradermic suture was made using a 5-0 Coated VICRYL absorbable suture. Superficial electron irradiation was implemented 10-22 h postoperatively. The dose of radiation was 4 Gy each time, with the frequency of 4-5 times in 4-7 days, once a day, and the total dose was up to 16-20 Gy.@*Results@#The average follow-up was 15 months (12-18 months). Based on the three-stage classification system formulated by Dr. Cai, an asymptomatic flat and soft scar without recurrence up to 12 months was classified as cured (excellent). All the patients in this series met the criterion of cure.@*Conclusions@#The distal subcutaneous buried suture technique, pulling bilateral normal skin toward the center with a PDS Ⅱ suture, could completely relax the skin around the incision, and maintain a prolonged tension-free state, combination therapy of electron irradiation and surgery may reduce the inflammation during the healing process, and result in a dramatic inhibition of the recurrent of keloids after surgery.
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@#Twophoton microscopy is a new technique which combines laser scanning con-focal microscopy and two-photon excitation technique. Two-photon fluorescence microscopy has the advantages of little light damage, small bleaching area, strong penetrability, high resolution, high fluorescence collection efficiency, and high image contrast. It is suitable for dark field imaging and multi-labeled compound measurement, and has been widely used in small animals in vivo optical imaging, such as research for tumour, gene therapy, stem cells, drug development, spinal cord injury, etc.
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@#MicroRNAs are short non-coding RNAs that regulate and control the translation of target genes, and play an important role in gene expression involved in the development of spinal cord and spinal cord injury, which constitute novel targets for therapeutic intervention to promote repair and regeneration of the spinal cord, also they are the potential biomarkers of spinal cord injury. This article reviewed the mechanism of microRNAs and listed several microRNAs in spinal cord injury area.
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@# Tethered cord syndrome (TCS) is a progressive neurodevelopmental disorder. The TCS model was established mainly using physical and chemical Methods and surgery, but remained problems in failing to fully reflect the progressive course of the human TCS. In the future, it may select a single etiological factor to analyze, and gradually add other factors until we have deeper understanding of this disease.
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With the development of science and technology, and the emergence of artificial intelligence, wearable technology is becom-ing a hot topic in the field of rehabilitation medicine. Wearable technology is characterized by miniaturization, intelligency and convenience, and has been widely researched and applied in many fields, such as neurological rehabilitation, orthopaedic rehabilitation, spinal cord injury rehabilitation and rehabilitation for senile degenerative diseases. The further research may focus on the reliability of signals under dynamic monitoring, the comfortable feeling during long-term use of wearable devices, the data security based on personal privacy, and so on.
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Objective To investigate the value of intravoxel incoherent motion MR imaging (IVIM-MRI)on monitoring impairment of renal function in hydronephrosis.Methods Left hydronephrosis model of Healthy New-Zealand rabbits made by ureteral incomplete obstruction were scanned by IVIM-MRI at 4, 8, 12, and 16 weeks.The change of IVIM-MRI quantitative parameters (ADC values, D values, D* values, and f values) in left hydronephrosis kidney were observed.The correlation between these parameters and glomerular filtration rate (GFR) were evaluated.Results ADC values, D values, D* values and f values at cortex and medulla in left hydronephrosis model of rabbits decreased gradually in the progression of renal damage after 4, 8, 12, and 16 weeks.For D value, f value and ADC values, there was statistical significant difference among the group of 12 weeks, the group of 16 weeks, the control group, and the group of 4 weeks;statistical significant difference was also observed between the group of 8 weeks and the group of 16 weeks by LSD contrast.ADC values, D values, D* values, and f values were positively correlated to GFR at 4, 8, 12, and 16 weeks for left hydronephrosis model of rabbits.Conclusion IVIM-MRI could monitor impairment of renal function in hydronephrosis dynamically.
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Objective To explore the expression of miRNA-181a (miR-181a) in patients with multiple myeloma (MM) and its effect on biological features of MM cells. Methods CD138+cells of bone marrow from 25 MM patients and 10 patients with hematological non-malignancies were purified by using immunomagnetic separation, and the expression of miR-181a in CD138+cells and MM cell lines including RPMI 8226, H929 and U266 were detected by real-time quantitative PCR. The effects of down-regulation and up-regulation of miR-181a expression on the biological characteristics of MM cells were studied with miR-181a antagomir and agomir. Results Compared with patients with hematological non-malignant diseases, the expression of miR-181a in CD138+ cells was upregulated in MM patients. Compared with CD138+ cells in hematological non-malignancies, high expressions of miR-181a were observed in RPMI 8226 and U266 myeloma cell line, while low expressions of miR-181a were observed in H929 cells. Down-regulation of miR-181a with 100 nmol/L miR-181a antagomir could inhibit the proliferation of U266 cells at 24,48 and 72 h [(67.1 ± 3.3) %vs. (50.5 ± 4.1) %, (71.5 ± 3.6) % vs. (52.3 ± 2.2) %, (78.1 ± 5.4) % vs. (69.5 ± 4.3) %, P < 0.05 respectively], whereas up-regulation of miR-181a with 100 nmol/L miR-181a agomir could significantly promote the proliferation of H929 cells at 24 h and 48 h [(21.2 ± 2.4) %vs. (38.5 ± 3.6) %, ( 61.3 ± 5.4) %vs. (82.2 ±6.9)%, P<0.01 respectively]. Cell cycle analysis showed that miR-181a antagomir made U266 cell cycle arrest in the G0/G1 phase. Meanwhile, susceptibility test results indicated that the apoptosis of U266 cells induced by doxorubicin, paclitaxel and 5-fluorouracil was increased when the proliferation of miR-181a expression was down-regulated with miR-181a antagomir. In migration assay, the data showed that down-regulation of miR-181a with miR-181a antagomir could inhibit the migration of U266 cells, and the proportion of migrated cells in the experimental group (62 ± 10) %was lower than that in the control group (89 ± 12) %(P< 0.05), whereas up-regulation of miR-181a with miR-181a agomir could improve the migration of H929 cells, and the proportion of migrated cells in the experimental group (242 ± 9) % was higher than that in the control group (98 ± 8)%(P<0.01). Conclusions The high expression of miR-181a expressed highly by MM cells may promote the proliferation, migration and drug resistance of myeloma cells, indicating that miR-181a could be an important prognostic biomarker candidate, and the application of gene silencing may improve the prognosis of MM.
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The measurement of intramedullary pressure is particularly important in the research of spinal cord injury. This article ana-lyzed the influence factors and the measurement methods of intramedullary pressure. The influence factors included edema, vascular regula-tion and bleeding, spinal dural, pia mater spinalis, cerebrospinal fluid, canalis vertebralis and body position, etc. The measurement methods included direct measurement methods, as the sensor placed in the parenchyma of spinal cord, intradural extramedullary or lumbar catheter, and measuring in vitro, and indirect measurement methods, as computer modeling and intraocular pressure measuring.
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Objective To analyze the expression feature and function of microRNAs in exosomes secreted by leukemia cells (LCEX). Methods The mice leukemia cell line L1210 was taken as the example, and LCEXL1210 was obtained by isolating supernate of L1210 cells through density gradient centrifugation. MicroRNAs isolated from LCEXL1210 were analyzed by microarray analysis, compared with miRNA from L1210 cell line, and then some of miRNAs with different expression were verified by real-time PCR and were analyzed by Gene Ontology (GO) database. Results The number of miRNAs identified in LCEXL1210 was 1 044, and that in L1210 cell line was 872. The number of shared miRNAs between LCEXL1210 and L1210 cell line was 732, accounting for 70.1 % of LCEXL1210 and 83.9 % of L1210 cell line, respectively, which indicated that 70 % of LCEXL1210 was derived from the parental cells. Interestingly, 312 miRNAs in LCEXL1210 were found to be underrepresented in the parental cells, indicating their specificity in LCEXL1210. Some miRNAs were significantly highly expressed in LCEXL1210 compared with those in L1210 cell line, including miR-16-1, miR-210, miR-195 and so on, which showed that miRNAs isolated from LCEXL1210 were differentially expressed with those from the parental cells. Some differentially expressed miRNAs from LCEXL1210 were verified by real-time PCR, and then were analyzed by GO database, which demonstrated that these highly expressed miRNAs participated in the processes of various biological function and signal transduction. Conclusions MiRNAs isolated from LCEXL1210 show a high similarity to miRNAs isolated from L1210 cells, whereas of which one-third are specific. The highly expressed miRNAs participate in the processes of various biological function and signal transduction.
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Objective To identify the expression of transcription factor Sp1 in NK/T-cell lymphoma (NK/TCL) cell lines and to investigate the role of Sp1 in regulation of cell invasion. Methods Real-time PCR, immunofluorescence and Western blot were performed to detect the expression of Sp1 in NK/TCL cell lines SNK-1 and SNK-6 and normal NK cells. Expression levels of IGF-1R and MMP-2 were measured by real-time PCR and Western blot, respectively. Transwell assay was applied to observe the effects of mythramycin A(MIT) on cell invasion. Results Sp1 expression in mRNA and protein were over-expression in NK/TCL cell lines SNK-1 and SNK-6 when compared with normal NK cells. Inhibition of Sp1 by MIT remarkably reduced expression of IGF-1R and MMP-2 in SNK-1, SNK-6 and as a result, or significantly suppressed cell invasion. Expression levels of Sp1 mRNA in SNK-1 and SNK-6 were (9.4±0.3) and (10.6±0.3) foldsincrease as compared with that of control group, respectively (P=0.005 2, P=0.003 7). Levels of Sp1 protein were (5.4±0.3) and (8.6±0.5) foldsincrease times than control groups, respectively (P=0.008 3, P=0.006 9). Inhibition of Sp1 by MIT (100 nmol/L) remarkably reduced expression levels of IGF-1R mRNA by (83.9±3.7) % and (65.8±4.2) % (P = 0.008 2, P = 0.009 7) as compared with controls. Meanwhile, levels of IGF-1R protein were reduced by (51.5±7.1) % and (49.6±9.1) % (P = 0.017 8, P = 0.015 5) as compared with control group. Inhibition of Sp1 by MIT (100 nmol/L) significantly reduced cell invasion and MMP-2 expression in the two cell lines,the cell invasion rates were reduced by (29.6±6.4) % and (37.2±7.6) % (P =0.041 8, P = 0.037 2) in SNK-1 and SNK-6 as compared with control group. The MMP-2 protein levels were found to be (52.7±4.7) % and (29.7±5.6) % (P = 0.028 6, P = 0.020 2) of control group. Conclusion Sp1 is over-expressed in NK/TCL cell lines, and it promotes NK/TCL cell invasion by up-regulating IGF-1R and further increasing MMP-2 expression.
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<p><b>OBJECTIVE</b>To understand the distribution of both HBsAg and HBsAb negative adults in Mianyang, Sichuan province, and provide evidences for the development of adult immunization policy.</p><p><b>METHODS</b>From June 2013 to April 2014, a total of 200 929 people aged ≥15 years were selected in Mianyang through stratified cluster random sampling to conduct an interview with standard questionnaire. The blood samples were collected from them for the detection of HBsAg and HBsAb with enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Among the people surveyed, 13 903 were HBsAg positive (7.0%), 93 763 were HBsAb positive (46.6%), and 93 122 were both HBsAg and HBsAb negative (46.3%). The negative rate of both HBsAg and HBsAb in females (47.1%) was higher than that in males (45.4%). The negative rate of both HBsAg and HBsAb increased with age. The negative rate of both HBsAg and HBsAb was highest in people aged ≥65 years (50.3%) and lowest in people aged 15-24 years (42.9%). The negative rate of both HBsAg and HBsAb was highest in farmers (51.1%) and lowest in medical workers (24.1%). The negative rate of both HBsAg and HBsAb was highest in the widowed (51.1%) and lowest in the unmarried (41.6%). The negative rate of both HBsAg and HBsAb was lower in people with family history of hepatitis B (36.5%) than in people without family history of hepatitis B (46.6%). The negative rate of both HBsAg and HBsAb in Han ethnic group was lower (46.3%) than that in Qiang ethnic group (53.1%), but higher than that in other ethnic groups (43.9%). The negative rate of both HBsAg and HBsAb was higher in rural area (48.9%) than in urban area (43.0%). The negative rate of both HBsAg and HBsAb was lower in people who had received hepatitis B immunization (43.7%) than in people who had received no hepatitis B immunization (47.3%). The differences were all statistical significant (P<0.01).</p><p><b>CONCLUSION</b>The negative rate of both HBsAg and HBsAb was 46.3% in people aged ≥15 years in Mianyang. General population are susceptible to hepatitis B virus infection. It is necessary to develop and implement appropriate hepatitis B immunization strategy for local adult population.</p>
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Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , China , Epidemiology , Enzyme-Linked Immunosorbent Assay , Ethnicity , Health Personnel , Hepatitis B , Epidemiology , Hepatitis B Antibodies , Blood , Hepatitis B Surface Antigens , Blood , Hepatitis B Vaccines , Hepatitis B virus , Seroepidemiologic Studies , Surveys and Questionnaires , VaccinationABSTRACT
Objective To identify the expression pattern of IGF-1 and IGF-1R in NK/T-cell lymphoma (NK/TCL) cell lines and to investigate the role of IGF-1/IGF-1R signaling in regulation of cell migration and invasion.Methods RT-PCR and immunofluorescence were performed to detect the expression of IGF-1 and IGF-1R.Transwell assay was applied to observe the effects of IGF-1/IGF-1R signaling and downstream kinases activities on cell migration and invasion.Concentrations of MMP-2 and MMP-9 were quantified by ELISA.Results Co-expression of IGF-1 and its receptor IGF-1R were identified in two NK/TCL cell lines,SNK-1 and SNK-6,while normal NK cells lack the IGF-1R expression.IGF-1R inhibitors significantly reduced SNK-1 and SNK-6 cells migration and invasion rates.Exogenous IGF-1 promoted both cell lines migration and invasion,but these effects were both blocked by IGF-1R inhibitors.Inhibition of AKT,p38 and JNK,the possible IGF-1R downstream kinases,reduced cell migration rates.Further more,exogenous IGF-1 significantly increased MMP-2 and MMP-9 secretion,while decreased secretion of MMP-2 and MMP-9 were observed when IGF-1R inhibitors were applied.Conclusion An autocrine IGF-1/IGF-1R signaling loop is aberrantly expressed on NK/TCL cells and the autocrine loop significantly promotes cell migration and invasion through activation of p38,PI3K and JNK signaling and enhances secretion of MMP-2 and MMP-9.