Correlations of expressions of tissue inhibitor of matrix metalloproteinase-1 and fibronectin 1 in pregnancy associated breast cancer with expression of E-cadherin and prognosis / 肿瘤研究与临床

Objective:To investigate the expressions of tissue inhibitor of matrix metalloproteinase-1 (TIMP1) and fibronectin 1 (FN1) in pregnancy associated breast cancer (PABC) and their correlations with expression of E-cadherin (E-cad).Methods:The clinicopathological data of 55 PABC patients in Binzhou People's Hospital Affiliated to Shandong First Medical University from January 2011 to December 2020 were retrospectively analyzed. Immunohistochemistry was used to detect expressions of TIMP1, FN1 and E-cad in cancer tissues and corresponding paracancerous tissues (>3 cm from the edge of the tumor foci). The expressions of TIMP1 and FN1 proteins in fresh intraoperative frozen cancer tissues and paracancerous tissues of 10 PABC patients were detected by Western blotting. The correlations of TIMP1 and FN1 expressions with clinicopathological characteristics of patients were analyzed by χ2 test, the correlation of TIMP1 and FN1 expressions with E-cad expression was analyzed by Spearman method, and the correlation of TIMP1 and FN1 expressions with survival was analyzed by Kaplan-Meier method. Results:The positive rates of TIMP1 and FN1 in PABC tissues were 72.7% (40/55) and 58.2% (32/55), and 25.5% (14/55) and 18.2% (10/55) in paracancerous tissues, and the differences were statistically significant ( χ2 values were 24.59 and 18.64, both P < 0.001). The results of Western blotting showed that the relative expressions of TIMP1 and FN1 proteins in the fresh cancer tissues of 10 PABC patients was higher than those in the corresponding paracancerous tissues (1.60±0.76 vs. 0.62±0.29, 1.31±0.62 vs. 0.44±0.15), and the differences were statistically significant ( t values were 5.92 and 4.86, both P < 0.001). The expressions of TIMP1 and FN1 in PABC tissues were correlated with estrogen receptor expression, Ki-67 positivity index, TNM stage and lymph node metastasis (all P < 0.05). The expressions of TIMP1 and FN1 were negatively correlated with expression of E-cad in PABC ( r values were -0.471 and -0.432, both P < 0.001). Five cases were lost to follow-up, and the remaining 50 cases had a median follow-up time of 43 months (12-90 months). Among the 50 cases, 36 cases were TMP1-positive and 29 cases were FN1-positive. The overall survival of TIMP1-negative group and FN1-negative group were better than those of the corresponding positive group ( χ2 values were 4.49 and 6.06, both P < 0.05); the median overall survival time of TIMP1-positive group and FN1-positive group were 51 months (95% CI 37-65 months) and 43 months (95% CI 32-53 months), while that of TIMP1-negative group and FN1-negative group were 89 months (95% CI 84-93 months) and 87 months (95% CI 85-92 months). Conclusions:TIMP1 and FN1 expressions are elevated in PABC tissues and negatively correlated with E-cad expression, TIMP1 and FN1 may be involved in PABC invasion through epithelial-mesenchymal transition and affect the prognosis of patients.

Identification the key factor of pulmonary fibrosis following silica nanoparticles exposure based on bioinformatics analysis / 中华劳动卫生职业病杂志

Objective: To investigate the main mechanisms of pulmonary fibrosis following silica nanoparticles (SiNPs) exposure through constructing the macrophage-fibroblast model in vitro, which simulated the process of pulmonary fibrosis. Methods: In January 2021, human mononuclear leukemia cells (THP-1) were treated with 0, 25, 50, 100 μg/ml SiNPs for 24 h. The supernatant of THP-1 cells was collected and applied to human embryonic lung fibroblast cells (MRC-5) which divided into control and low, medium and high dose groups at the logarithmic growth stage for 24 h. MRC-5 cell viability was detected by CCK8. The hydroxyproline (Hyp), interleukin 6 (IL-6), interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) expression were detected in the supernatants of MRC-5. The changed proteins were detected by liquid-phase mass spectrometry in high dose group. GeneCard database were applied to identity the differential pulmonary fibrosis proteins in high dose group. Gene Ontology (GO) was performed to identity the key biological process in differential pulmonary fibrosis proteins of high dose group. The String database was used to construct the protein-protein interactions (PPI) network of differential pulmonary fibrosis proteins. The APP of CytoHubba was applied to calculate the key protein of differential pulmonary fibrosis proteins in PPI network. Correlation coefficients between key differential pulmonary fibrosis proteins were calculated using Pearson correlation analysis. Western blotting was applied to detect the expression of key proteins of differential pulmonary fibrosis proteins in different groups. Results: CCK8 results showed that MRC-5 cell viability was increasing in low, medium and high dose groups compared with control group (P<0.05). The expression levels of Hyp and IL-1β in different group were increased compared with control group, the expression levels of IL-6 and TNF-α were increased in high dose group compared with control group (P<0.05). GeneCard database identified 26 differential pulmonary fibrosis proteins, which were mainly involved in extracellular matrix hydrolysis, cell inflammatory response, tissue repair, cell proliferation, inflammation response by GO analysis. The APP of CytoHubba was calculated that matrix metalloproteinase 9 (MMP9) and tissue inhibitor metalloproteinase 1 (TIMP1) played an important role in PPI network. The results of correlation analysis showed that MMP9 was correlated with the expression of matrix metalloproteinase 1 (MMP1), matrix metalloproteinase 3 (MMP3), TIMP1 and epidermal growth factor receptor (EGFR) (r=0.97, 0.98, 0.94, 0.93, P<0.05). Western blotting results showed that TIMP1 protein expression was increased in low, medium and high dose groups, while MMP9 protein expression was increased only in high dose group (P<0.05) . Conclusion: Differential expression proteins related with pulmonary fibrosis in MRC-5 cells mainly regulate biological processes of extracellular matrix hydrolysis, tissue repair, and cellular inflammation response following SiNPs exposure. MMP9 and TIMP1 may be the key proteins, which affected the fibrosis process in vitro pulmonary fibrosis model.

Association of matrix metalloproteinase-1-1607 1G/2G single nucleotide polymorphism genotypes with periodontitis in Iraqi population / Associação entre genótipos de polimorfismo de nucleotídeo único de metaloproteinase-1-1607 1G/2G da matriz e periodontite em população iraquiana

Objective and background: Periodontitis is an inflammatory disease which is characterized by a progressive loss in the matrix of soft and hard tissue of periodontium particularly the collagen fibers which are cleaved by matrix Metalloproteinase (MMP). Indeed, increased activity of MMP mediates progression of periodontal diseases but population-based genetic variations could determine the susceptibility to the disease. The aim was to investigate association between MMP-1-1607 polymorphism with periodontitis among Iraqi individuals. Subjects and methods: The design of this study was a case-control for Iraqi individuals who were divided into two groups; periodontitis group (cases) and those with healthy periodontium (Control). For each subject, clinical periodontal parameters and demographic characteristics were recorded and venous blood was withdrawn for genetic analysis of MMP-1 by using PCR technique and DNA sequencing. Results: Analysis of MMP-1-1607 genotypes, by Hardy-Weinberg equilibrium, showed significant differences in the total sample. The most predominant MMP-1-1607 genotype among Controls was 1G/2G which was significantly different from periodontitis cohorts. Overall, 13 SNP were detected in periodontitis group versus 17 SNP in Control group. In addition, the periodontitis group showed a significant negative association between the probing pocket depth and MMP-1-1607. Conclusion: Results suggested that polymorphisms in MMP-1-1607 1G/2G may play a protective role and decreasing the susceptibility to periodontitis. (AU)

Introdução e objetivo: A periodontite é uma doença inflamatória caracterizada pela perda progressiva da matriz dos tecidos moles e duros do periodonto, particularmente as fibras de colágeno clivadas pelas metaloproteinases da matriz (MMPs). De fato, o aumento da atividade de MMPs medeia a progressão das doenças periodontais, mas as variações genéticas baseadas na população podem determinar a suscetibilidade à doença. O objetivo foi investigar a associação entre o polimorfismo MMP-1-1607 e periodontite em indivíduos iraquianos. População e método: O desenho deste estudo foi um caso-controle com indivíduos iraquianos, os quais foram divididos em dois grupos: grupo periodontite (casos) e indivíduos com periodonto saudável (controle). Para cada sujeito, os parâmetros clínicos periodontais e as características demográficas foram registrados, e o sangue venoso foi coletado para análise genética de MMP-1 por meio da técnica de PCR e sequenciamento de DNA. Resultados: A análise dos genótipos MMP-1-1607, pelo equilíbrio de Hardy-Weinberg, mostrou diferenças significativas na amostra total. O genótipo MMP-1-1607 mais predominante entre os controles foi 1G/2G, o qual foi significativamente diferente das coortes de periodontite. No geral, 13 SNP foram detectados no grupo periodontite versus 17 SNP no grupo controle. Além disso, o grupo periodontite mostrou uma associação negativa significativa entre a profundidade da bolsa de sondagem e MMP-1-1607. Conclusão: Os resultados sugerem que polimorfismos em MMP-1-1607 1G/2G podem desempenhar um papel protetor e diminuir a suscetibilidade à periodontite. (AU)

Association between matrix metalloproteinase-1 (MMP-1) protein level and the risk of rheumatoid arthritis and osteoarthritis: a meta-analysis

Recent publications have investigated the potential role of the protein level of matrix metalloproteinase-1 (MMP-1) in the susceptibility to rheumatoid arthritis (RA) and osteoarthritis (OA). However, no unanimous conclusion was obtained. Therefore, we carried out a meta-analysis to explore the association between MMP-1 expression and these two clinical disorders. After database searching and screening, we enrolled a total of eighteen articles for the pooled analysis. We observed a significant association between RA cases and controls in the whole population [SMD (standard mean difference)=1.01, P=0.017]. There were similar positive results in the subgroup analysis of "population-based control" (SMD=1.50, P=0.032) and "synovial fluid" (SMD=1.32, P=0.049). In addition, we observed an increased risk in OA cases, compared with controls, in the overall analysis (SMD=0.47, P=0.004) and subsequent subgroup analysis of "knee OA" (SMD=0.86, P<0.001), "Asian/China" (SMD=0.76, P=0.003), "cartilage-Asian/China" (SMD=1.21, P<0.001), and "synovial fluid-Asian/China" (SMD=0.73, P=0.004). In summary, a high protein level of MMP-1 in synovial fluid may be associated with the susceptibility to RA, and the high MMP-1 level in the cartilage tissue or synovial fluid may be related to the pathogenesis of knee OA in the Chinese population. This should be confirmed by larger sample sizes.

Effects of different negative pressure suction devices on collagen, MMP-1 and TGF-β secretion of skin / 中华医学美学美容杂志

Objective:To compare the effects of circular arch device and dressing device on the secretion of collagen, matrix metalloproteinase (MMP-1), transforming growth factor (TGF-β) of fibroblasts in the treated skin, and to explore the changes and mechanisms.Methods:The animals were purchased from the Southern Medical University Laboratory Animal Center. Using the established animal model, 54 mice were randomly divided into three groups: 18 mice each group, including control group, dressing device group and and circular arch device group. At the first, third and fifth day after negative pressure suction treatment, dermal thickness and density of collagen levels were and eosin staining, collagen level in local skin was determined using spectrophotometry, and MMP-1 and TGF-β levels were determined using enzyme linked immunosorbent assay.Results:Dermal thickness level was increased significantly in negative suction treated groups [after 5 days of treatment, control group: (71±8) μm; circular arch device group: (351±9) μm; dressing device group: (267±12) μm, P< 0.05]. Compared with the control group, collagen level in the dermis was significantly higher in circular arch device groups [after 5 days of treatment, control group: (30.9±4.3) mg/g; circular arch device group: (72.7±3.6) mg/g, P< 0.05]. TGF-β level in circular arch device treated group was increasing gradually, and markedly higher than that in the dressing device group and the control group [after 5 days of treatment, control group: (0.24±0.1) ng/ml; circular arch device group: (0.78±0.08) ng/ml; dressing device group: (0.39±0.18) ng/ml, P< 0.05], while MMP-1 level was decreasing. In addition, TGF-β and MMP-1 levels in the dressing device treated group remained stable during the entire experiment. Conclusions:The interface of the circular arch negative pressure suction device can effectively activate the fibroblasts, promote the secretion of TGF-β and collagen, and thicken the skin tissue.

Changes of collagen and MMP-1 in liver, lung and kidney during growth of mice / 生物工程学报

The high performance liquid chromatography (HPLC) and enzyme-linked immunoassay (ELISA) were used to investigate the changes of collagen and matrix metalloproteinase-1 (MMP-1) in liver, lung and kidney during growth process of mice. The mice from 0 to 18 weeks were used as the research objects. The contents and proportions of hydroxyproline (Hyp), which were used to calculate the collagen contents, in liver, lung and kidney of different weeks were analyzed with HPLC. The contents and activity of MMP-1 in liver, lung and kidney of different weeks were analyzed with ELISA. The results showed that the collagen contents in liver, lung, and kidney were different (Lung(COL)>Kidney(COL)>Liver(COL)), and they all increased first and then decreased with weeks. The collagen contents in liver, lung, and kidney reached the highest level in the ninth (5.52 ng/mg), sixth (54.10 ng/mg) and ninth (19.20 ng/mg) week, respectively. Then it declined slowly from 9 to 18 weeks. The result of ELISA showed that the MMP-1 contents in liver, lung and kidney decreased first and then increased with weeks, and the trend of MMP-1 activity was opposite. It indicated that the increase of collagen contents in the tissues will inhibit the secretion of MMP-1.

Analysis of TIMP-1 expression in leukoplakia and oral squamous cell carcinoma / Análise da expressão de TIMP-1 em leucoplasia e carcinoma de boca de células escamosas

ABSTRACT Introduction: The current study about transition of oral epithelial dysplasia, present in lesions such as leukoplakia, for squamous cell carcinoma (SCC) involves not only the histopathological aspects, but also the analysis of the presence of biomarkers which influence the microenvironment where cells are embedded. Objective: To evaluate the tissue inhibitor of metalloproteinase-1 (TIMP-1) profile in cases of leukoplakia and SCC classified into different degrees of dysplasia and histological grading, respectively. The immunohistochemical findings were confronted with microscopic features adopted in the classification of each lesion. Material and methods: Cases of leukoplakia and SCC were recovered from files of The Oral Pathological Anatomy Service of the Dental School at the Universidade Federal do Espírito Santo (SAPB-UFES), between the years 2004 and 2010. New slides were obtained and submitted to immunohistochemical assay to determine TIMP-1 expression profile. Parenchyma, as well as the different layers of the epithelium and stroma was evaluated. Results: In all cases the presence of TIMP-1 was detected in the stroma and parenchyma. In mild leukoplakia, the basal layer with hyperplasia showed intense immunolabeling, whereas cells with loss of polarity presented weaker expression. In moderate leukoplakia, all epithelium layers, except the cornea, were labeled. Severe leukoplakia had the spinous layer most intensely labeled, with no variation in areas with pleomorphism. Stage I SCC showed the deepest islands with intense labeling in cells with pleomorphism and mitoses. In the tumor islands, less differentiated cells were weakly labeled, and in keratin pearl, labeling was weak or absent in central cells. In stage II SCC, labeling was observed in basal cell with hyperplasia and in cells of the spinous layer, however, the parabasal layer was not labeled. Also, on tumor islands, less differentiated cells did not express the protein and keratin pearls were not labeled. Conclusion: It was possible to detect TIMP-1 immunolabeling in all specimens, ranging in intensity and location. The absence of expression in less differentiated cell suggests that more aggressive lesions present reduced enzyme expression. The microenvironment is important for the various cellular activities, and TIMP is an enzyme that participates in matrix remodeling, therefore changes in its expression can be a valuable tool in the better understanding oral carcinogenesis.

RESUMEN Introducción: El estudio actual de la transición de displasia epitelial oral, presente en lesiones como la leucoplasia, hacia carcinoma epidermoide, implica no solo aspectos histopatológicos, sino también el análisis de la presencia de biomarcadores que influyen en el microambiente en el que se insertan las células. Objetivo: Evaluar el perfil del inhibidor tisular metaloproteinasa-1 (TIMP-1) en casos de leucoplasia y carcinoma de células escamosas (CCE) clasificados en diferentes grados de displasia y grados histopatológicos, respectivamente. Confrontar los hallazgos inmunohistoquímicos con los aspectos microscópicos adoptados en la clasificación de lesiones. Material y métodos: Casos de leucoplasia y CCE fueron recuperados del Servicio de Anatomía Patológica Bucal del Curso de Odontología de la Universidad Federal de Espírito Santo (SAPB-UFES), entre los años 2004-2010. Se obtuvieron nuevos portaobjetos y se los sometieron a ensayos inmunohistoquímicos para determinar el perfil de expresión de TIMP-1. Se evaluó el parénquima, así como las diferentes capas del epitelio y estroma. Resultados: En todos los casos se detectó TIMP-1 en estroma y parénquima. En la leucoplasia leve, la capa basal y con hiperplasia mostró inmunotinción intensa, mientras que las células con pérdida de polaridad tuvieron menos expresión. En la leucoplasia moderada, todas las capas del epitelio, excepto la córnea, mostraron inmunotinción. En la leucoplasia grave la capa espinosa tuvo inmunotinción más intensa, sin variación en áreas con pleomorfismo. El CCE grado I mostró las islas más profundas con tinción intensa en células con pleomorfismo y mitosis. En las islas tumorales, las células menos diferenciadas tuvieron tinción menor, y en las perlas de queratina la tinción fue débil o ausente en las células centrales. En el CCE grado II, se observó tinción en células basales con hiperplasia y, en células de la capa espinosa, la capa parabasal no fue marcada. También en las islas, las células menos diferenciadas no expresaron la proteína y no hubo tinción en las perlas de queratina. Conclusión: Fue posible detectar inmunotinción para TIMP-1 en todos los especímenes, con variación en intensidad y ubicación. La ausencia de expresión en células menos diferenciadas sugiere que las lesiones más agresivas tienen enzima reducida. El microambiente es importante para las diversas actividades celulares, y el TIMP es una enzima que participa en la remodelación de la matriz; por lo tanto, la alteración en su expresión puede ser una herramienta valiosa en el mejor entendimiento de la carcinogénesis de la mucosa oral.

RESUMO Introdução: O estudo atual da transição da displasia epitelial oral, presente em lesões como a leucoplasia, para o carcinoma de células escamosas (CCE), envolve não somente aspectos histopatológicos, como também a análise da presença de biomarcadores, os quais influenciam o microambiente em que as células estão inseridas. Objetivo: Avaliar o perfil da expressão do inibidor tecidual de metaloproteinase 1 (TIMP-1) em casos de leucoplasias e CCE classificados em diferentes graus de displasia e graus histopatológicos, respectivamente, e confrontar os achados imuno-histoquímicos com os aspectos microscópicos adotados na classificação das lesões. Material e métodos: Foram resgatados casos de leucoplasia e CCE do Serviço de Anatomia Patológica Bucal do curso de Odontologia da Universidade Federal do Espírito Santo (SAPB-UFES), entre os anos 2004-2010. Novas lâminas foram obtidas ao serem submetidas ao ensaio imuno-histoquímico para determinação do perfil de expressão de TIMP-1. Foram avaliados parênquima, bem como as diferentes camadas do epitélio e estroma. Resultados: Em todos os casos, foi detectada a presença de TIMP-1 no estroma e no parênquima. Na leucoplasia leve, a camada basal e com hiperplasia apresentou imunomarcação intensa; as células com perda de polaridade tiveram expressão menor. Na leucoplasia moderada, todas as camadas do epitélio, exceto a córnea, apresentaram marcação. A leucoplasia severa teve a camada espinhosa marcada mais intensamente, sem variação em áreas com pleomorfismo. O CCE grau I apresentou as ilhas mais profundas com marcação intensa em células com pleomorfismo e mitoses. Nas ilhas tumorais, células menos diferenciadas tiveram marcação menor, e em pérolas córneas a marcação foi fraca ou ausente nas células centrais. No CCE grau II, foi observada a marcação em células basais com hiperplasia e, em células da camada espinhosa, a camada parabasal não foi marcada. Também nas ilhas, células menos diferenciadas não expressaram a proteína e não houve marcação em pérolas córneas. Conclusão: Foi possível detectar imunomarcação para TIMP-1 em todos os espécimes, com variação em intensidade e localização. A ausência de expressão em células menos diferenciadas sugere que lesões mais agressivas possuem redução da enzima. O microambiente é importante para as diversas atividades celulares, e TIMP é uma enzima que participa da remodelação da matriz. Portanto, alteração na sua expressão pode ser uma valiosa ferramenta para um melhor entendimento da carcinogênese da mucosa bucal.

Correlation of the expression of the inflammatory cytokines and the pathological degree in patients with knee osteoarthritis / 中国组织工程研究

BACKGROUND: In the development of osteoarthritis, the mechanism underlying cartilage damage is still unclear. Matrix metalloproteinases have been shown to play important roles in cartilage matric degradation. OBJECTIVE: To observe the correlation between the expression of matrix metalloproteinase 3, tissue inhibitor of metalloproteinase-1 and the pathological degree in knee osteoarthritis. METHODS: The study was approved by the Ethics Committee of Shenyang Orthopedic Hospital. The tibial plateaus of 40 patients with knee osteoarthritis who underwent total knee arthroplasty were collected, and all patients signed the informed consents. The classification of osteoarthritis was evaluated according to Kellgren-Lawrence (KL) scale system: 11 cases of KL grade 2, 15 cases of KL grade 3, and 14 cases of KL grade 4. Control group contained six cases. Samples received hematoxylin-eosin staining. The pathological changes of knee osteoarthritis cartilage were evaluated by Mankin score. Immunohistochemical staining was used to detect the contents of matrix metalloproteinase 3 and tissue inhibitor of metalloproteinase-1 in cartilage. RESULTS AND CONCLUSION: (1) Hematoxylin-eosin staining results showed that in the control group, the layer of cartilage was thick, and there were abundant chondrocytes that arranged regularly. The subcutaneous layer of cartilage in the KL grade 2 group was rugged, and fissure was observed occasionally. Fibrosis of cartilage layer was visible in the KL grade 3 group, and the chondrocytes arranged in disorder. In the KL grade 4 group, the structure of cartilage layer was lost, and there were few chondrocytes that arranged irregularly. (2) Immunohistochemical staining results showed that the expression level of matrix metalloproteinase 3 in the osteoarthritis group was significantly higher than that in the control group. The expression level of matrix metalloproteinase 3 was on a rise in the KL grade 2, 3 and 4 groups (all P < 0.05). The expression level of tissue inhibitor of metalloproteinase-1 in the osteoarthritis group was significantly lower than that in the control group. The expression level of tissue inhibitor of metalloproteinase-1 was on a descent in the KL grade 2, 3 and 4 groups (all P < 0.05). (3) There was significantly positive correlation between matrix metalloproteinase 3 expression level and Mankin score (r=0.899, P < 0.001), and tissue inhibitor of metalloproteinase-1 expression level was negatively correlated with Mankin score (r=-0.903, P < 0.001). There was significantly negative correlation between tissue inhibitor of metalloproteinase-1 expression level and matrix metalloproteinase 3 expression level (f=-0.881, P < 0.001). (4) These results indicate that in the articular cartilage of patients with osteoarthritis, the expression levels of matrix metalloproteinase 3 and tissue inhibitor of metalloproteinase-1 are correlated with the pathological changes, which can be used as an effective index to evaluate the progress of knee osteoarthritis.

Therapeutic effect of human adipose stem cells derived exosomes on carbon tetrachloride induced liver fibrosis in rats / 中国组织工程研究

BACKGROUND: Liver fibrosis has higher morbidity and mortality. Activation and proliferation of hepatic stellate cells is a key link in the progression of liver fibrosis. At present, there are still no effective anti-fibrosis agents targeting single links or targets. OBJECTIVE: To analyze the effect of human adipose stem cells derived exosomes on rats with liver fibrosis induced by carbon tetrachloride. METHODS: Human adipose stem cells were obtained from healthy people by enzyme dissolution method. After in vitro culture, human adipose stem cells derived exosomes were obtained by multiple ultrafiltration. Different concentrations of exosomes were used to treat the hepatic stellate cells activated by transforming growth factor β1. The human adipose stem cells activated by transforming growth factor β1 were treated with different concentrations of exosomes. The expression of α-smooth actin in the cells was detected by quantitative PCR, and the growth and apoptosis of activated hepatic stellate cells were detected by CCK-8 and flow cytometry respectively. Rat models of liver fibrosis were established by intraperitoneal injection of carbon tetrachloride and treated by tail vein injection of exosomes. Rat liver function, serum levels of type III procollagen and type IV collagen, and Ishak score were determined. Semi-quantitative analysis of liver fibrosis was performed. The expression levels of tissue inhibitor of matrix metalloproteinase-1, matrix metalloproteinase 9 and α-smooth actin in liver tissue were measured by immunofluorescence method. The study protocol was approved by the Animal Ethics Committee and Medical Ethics Committee, Tongji University, China in January, 2017. RESULTS AND CONCLUSION: Human adipose stem cells derived exosomes inhibited the proliferation of activated hepatic stellate cells. The possible mechanism is to inhibit the proliferation of activated macrophages, reduce the production of collagen fibers, α-smooth actin actin, and tissue inhibitor of matrix metalloproteinase-1, and to increase the expression of matrix metalloproteinase 9. These findings suggest that exosomes can be used to treat carbon tetrachloride induced liver fibrosis.

Modified Xiaochaihu Decoction () Promotes Collagen Degradation and Inhibits Pancreatic Fibrosis in Chronic Pancreatitis Rats / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of Modified Xiaochaihu Decoction (MXD, ) on collagen degradation in rats with chronic pancreatitis (CP).@*METHODS@#Rats were injected dibutyltin dichloride (DBTC, 7 mg/kg of body weight) into the right caudal vein to induce CP model. Thirty heallhy male Wistar rats were randomly divided into three groups by a random number table: the control, the model and the treatment groups. Rats of treatment group were administered MXD (10 g/kg of body weight) orally once daily starting from the day post-model establishment. Pancreatic tissues were harvested after 28-day feeding and fibrosis was evaluated by picro-sirius red staining. The contents of collagen type I and III were detected using enzymelinked immunosorbent assay (ELISA), the expression of matrix metalloproteinase 13 (MMP13) and tissue inhibitor of metalloproteinase 1 (TIMP1) was analyzed by Western blot and real-time polymerase chain reaction (PCR).@*RESULTS@#The fibrosis scoring of pancreatic tissues, the concentrations of collagen type I and III, the expression levels of MMP13 and TIMP1 proteins and mRNA in the model group were all increased compared with the control group (P0.05).@*CONCLUSIONS@#MXD could promote collagen degradation and reverse pancreatic fibrosis in CP rats via a mechanism involve up-regulation of MMP13 expression.

Therapeutic effect of human adipose stem cells derived exosomes on carbon tetrachloride induced liver fibrosis in rats / 中国组织工程研究

BACKGROUND: Liver fibrosis has higher morbidity and mortality. Activation and proliferation of hepatic stellate cells is a key link in the progression of liver fibrosis. At present, there are still no effective anti-fibrosis agents targeting single links or targets.OBJECTIVE: To analyze the effect of human adipose stem cells derived exosomes on rats with liver fibrosis induced by carbon tetrachloride. METHODS: Human adipose stem cells were obtained from healthy people by enzyme dissolution method. After in vitro culture, human adipose stem cells derived exosomes were obtained by multiple ultrafiltration. Different concentrations of exosomes were used to treat the hepatic stellate cells activated by transforming growth factor β1. The human adipose stem cells activated by transforming growth factor β1 were treated with different concentrations of exosomes. The expression of α-smooth actin in the cells was detected by quantitative PCR, and the growth and apoptosis of activated hepatic stellate cells were detected by CCK-8 and flow cytometry respectively. Rat models of liver fibrosis were established by intraperitoneal injection of carbon tetrachloride and treated by tail vein injection of exosomes. Rat liver function, serum levels of type III procollagen and type IV collagen, and Ishak score were determined. Semi-quantitative analysis of liver fibrosis was performed. The expression levels of tissue inhibitor of matrix metalloproteinase-1, matrix metalloproteinase 9 and α-smooth actin in liver tissue were measured by immunofluorescence method. The study protocol was approved by the Animal Ethics Committee and Medical Ethics Committee, Tongji University, China in January, 2017. RESULTS AND CONCLUSION: Human adipose stem cells derived exosomes inhibited the proliferation of activated hepatic stellate cells. The possible mechanism is to inhibit the proliferation of activated macrophages, reduce the production of collagen fibers, α-smooth actin actin, and tissue inhibitor of matrix metalloproteinase-1, and to increase the expression of matrix metalloproteinase 9. These findings suggest that exosomes can be used to treat carbon tetrachloride induced liver fibrosis.

Effect of deuterium depleted water combined with platelet-rich plasma on wound healing of diabetic ulcer in rats / 上海交通大学学报（医学版）

Objective: To observe the effect of deuterium depleted water combined with platelet-rich plasma on wound healing of diabetic ulcer in rats, and to explore its possible mechanism. Methods: Male SD rats were randomly divided into two groups, normal control group (group A, n=20) and diabetic group (n=80). Rats in the diabetic group were fed with high-fat diet for 4 weeks, and the rat diabetic ulcer model was replicated by intraperitoneal injection of streptozotocin (STZ) + skin full-thickness resection; then randomly divided into diabetic model group (group B), platelet-rich plasma group (group C), deuterium depleted water group (group D), and deuterium depleted water combined platelet-rich plasma group (group E), with 18 rats for each group. Group A with common feed was fed for 4 weeks after intraperitoneal injection of an equal volume of citric acid-sodium citrate buffer + skin full-thickness resection to replicate the normal ulcer model. The animals were sacrificed after treatment for 3, 7 and 14 d, and the random blood glucose was measured at each corresponding time point. The wound surface and wound margin tissue were taken to observe the wound healing and local histomorphology of each group. The contents of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the wound tissue of each group were detected by enzyme-linked reaction adsorption method. Results: Random blood glucose in group D and group E was lower than that before intervention. The inflammatory response of the wounds in each diabetic group was slower than that in group A. The granulation ripening effect of group E was faster than that of group B, C, and D. The effect was best in each intervention group, and the neovascularization and fibroblasts appeared earlier and in large quantities. The content of TIMP-1 in group A was significantly higher than that in group B, C, D and E (P<0.05). The content of TIMP-1 in group B was significantly lower than that in group C, D and E (P<0.05). The content of TIMP-1 was significantly higher than that of group C and D (P<0.05). The content of MMP-9 in group B was significantly higher than that in group A, C, D and E (P<0.05). The content of MMP-9 in group E was significantly lower than that in group C and D (P<0.05). Conclusion: Deuterium depleted water can promote the healing of diabetic ulcer wounds. Deuterium depleted water combined with platelet-rich plasma can significantly promote the healing of diabetic ulcer wounds, which may be related to the decrease of random blood glucose, the increase of TIMP-1 and the inhibition of MMP-9 expression.

Esculetin Prevents the Induction of Matrix Metalloproteinase-1 by Hydrogen Peroxide in Skin Keratinocytes

BACKGROUND: Reactive oxygen species (ROS) are involved in various cellular diseases. Excessive ROS can cause intracellular oxidative stress, resulting in a calcium imbalance and even aging. In this study, we evaluated the protective effect of esculetin on oxidative stress-induced aging in human HaCaT keratinocytes. METHODS: Human keratinocytes were pretreated with esculetin for 30 minutes and treated with H₂O₂. Then, the protective effects on oxidative stress-induced matrix metalloproteinase (MMP)-1 were detected by Flou-4-AM staining, reverse transcription-PCR, Western blotting, and quantitative fluorescence assay. RESULTS: Esculetin prevented H₂O₂-induced aging by inhibiting MMP-1 mRNA, protein, and activity levels. In addition, esculetin decreased abnormal levels of phospho-MEK1, phospho-ERK1/2, phospho-SEK1, phospho-JNK1/2, c-Fos, and phospho-c-Jun and inhibited activator protein 1 binding activity. CONCLUSIONS: Esculetin prevented excessive levels of intracellular calcium and reduced the expression levels of aging-related proteins.

Effect of 3D-CRT combined with PC chemotherapy on non-small cell lung cancer patients and serum CA125, TIMP-1, SAA levels and immune function / 国际肿瘤学杂志

Objective@#To investigate the effect of three-dimensional conformal radiotherapy (3D-CRT) combined with PC chemotherapy (paclitaxel + carboplatin) on non-small cell lung cancer (NSCLC) patients and the serum levels of CA125, tissue inhibitor of metalloproteinase-1 (TIMP-1), serum amyloid A (SAA) and T-lymphocyte subsets.@*Methods@#A total of 100 patients with NSCLC treated in Affiliated Hospital of Guangdong Medical University from May 2015 to December 2017 were selected as the study subjects. They were divided into control group and observation group according to random number table method, with 50 cases in each group. The observation group was treated with 3D-CRT combined with PC chemotherapy, while the control group was treated with PC chemotherapy. The two groups were treated for 4 cycles. The therapeutic effect, serum CA125, TIMP-1, SAA, T-lymphocyte subsets and adverse reactions were compared between the two groups.@*Results@#Four cases were lost to follow-up both in the two groups. The overall response rate in the observation group (43.48%, 20/46) was higher than that in the control group (23.91%, 11/46; χ2=3.941, P=0.047). The serum levels of CA125, TIMP-1 and SAA of the two groups had no significant difference before treatment, and the levels of these indexes decreased after treatment. The serum levels of CA125, TIMP-1 and SAA in the observation group after treatment were (12.31±1.13) U/ml, (275.31±13.69) pg/ml and (47.21±7.21) mg/L, which were lower than those in the control group [(30.36±1.98) U/ml, (320.36±17.23) pg/ml, (65.92±8.36) mg/L], with significant differences (t=53.699, P<0.001; t=13.884, P<0.001; t=11.495, P<0.001). The levels of CD3+ , CD4+ , CD8+ and CD4+ /CD8+ of the two groups had no significant difference before treatment, and the levels of these indexes decreased after treatment. The levels of CD3+ , CD4+ , CD8+ and CD4+ /CD8+ in the observation group were (35.27±10.31)%, (20.27±6.72)%, (15.89±3.37)% and 0.91±0.37, which were higher than those in the control group [(30.77±9.27)%, (15.27±5.73)%, (12.02±2.69)% and 0.75±0.39], with significant differences (t=2.201, P=0.030; t=3.840, P<0.001; t=6.087, P<0.001; t=2.019, P=0.047). There were no significant differences in the adverse reactions such as nausea and vomiting [63.04% (29/46) vs. 43.48% (20/46); χ2=3.537, P=0.060], phlebitis [6.52% (3/46) vs. 4.35% (2/46); χ2=0.000, P>0.999], abnormal liver function [6.52% (3/46) vs. 2.17% (1/46); χ2=0.261, P=0.609] and myelosuppression [8.70% (4/46) vs. 6.52% (3/46); χ2=0.000, P>0.999] between the observation group and the control group.@*Conclusion@#For patients with NSCLC, 3D-CRT combined with PC chemotherapy can improve the overall response rate, decrease the levels of serum CA125, TIMP-1 and SAA, and improve the immune function of patients. The therapeutic effect is remarkable and the safety is good. The therapeutic scheme is suitable for the treatment of NSCLC.

Effect of Different Combinations of Gentianae Macrophyllae Radix on MMP-3 and TIMP-1 in Rheumatoid Arthritis Rats with Wind-cold-dampness Arthralgia / 中国实验方剂学杂志

Objective: To observe the effects of different combinations of Gentianae Macrophyllae Radix (Qinjiao) on the ankle joint matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) of rheumatoid arthritis (RA) model rats with wind-cold-dampness arthralgia.Method: Eighty healthy SD rats were randomly divided into 8 groups, namely blank control group, collage Ⅱ model group, wind-cold-dampness syndrome model group, positive control group, single-taste Gentianae Macrophyllae Radix group, Gentianae Macrophyllae Radix-Clematidis Radix et Rhizoma group (GC group), Gentianae Macrophyllae Radix-Taxilli Herba group (GT group), Gentianae Macrophyllae Radix-Stephanlae Tetrandrae Radix group (GS group), with 10 rats in each group. Rat model of wind-cold-dampness RA was induced through the injection with type Ⅱ collagen emulsion and wind-cold-dampness stimulation. After the establishment of the model, the blank control group, collage Ⅱ model group and wind-cold-dampness syndrome model group were given normal saline, and the corresponding liquid medicine was given to each administration group. In the experiment, the thickness of the left posterior metatarsal of rats was measured every 3 days, and the swelling degree of metatarsal was calculated. The arthritis index (AI) was evaluated on the 38th day of the experiment. The serum rheamatoid factor(RF) content of rats was detected by enzyme linked immunosorbent assay (ELISA). The expressions of MMP-3 and TIMP-1 in ankle joint were detected by Western blot. The expressions of MMP-3 and TIMP-1 mRNA in ankle joint were detected by real-time fluorescence quantitative PCR (Real-time PCR).Result: Compared with the blank group, the swelling degree, AI score, serum RF content, MMP-3 protein expression and MMP-3 mRNA expression in ankle joints of coll age Ⅱ model group and model wind-cold-dampness syndrome group were significantly increased (PPPPPPConclusion: For rheumatoid arthritis with wind-cold-dampness arthralgia, mild and warm traditional Chinese medicine (TCM) has a better effect than the combination of mild and cold TCM or mild TCM drugs. The experimental results are basically consistent with the principle of "treating cold diseases with hot medicine". The mechanism of the compatibility in treating rheumatoid arthritis due to wind-cold-dampness arthralgia may be related to the reduction of MMP-3, the increase of TIMP-1 expression and the reduction of articular cartilage damage.

Effect of anisodamine combined with blood purification on pulmonary fibrosis, serum matrix metalloproteinase-9 and matrix metalloproteinase 1 levels in patients with paraquat poisoning / 中国医师杂志

Objective@#To investigate the effect of anisodamine combined with blood purification on pulmonary fibrosis and levels of serum matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase 1 (TIMP1) in patients with paraquat poisoning.@*Methods@#From March 2013 to February 2017, 84 patients with paraquat poisoning admitted to our hospital were enrolled in the observation group (anisodamine + blood purification) or control group (blood purification ), 42 cases in each group. The curative effect, indexes related to pulmonary fibrosis, serum MMP-9 and TIMP1 levels were compared between the two groups. The incidence of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and intensive care uni (ICU) admission time were recorded.@*Results@#There was significant difference (P<0.05) in the total effective rate (88.1% vs 69.0%) and the high-resolution computed tomography (CT) score after 7 days of treatment (8.4±0.9 vs 12.3±1.4) between the observation group and the control group. At the same time, the serum levels of hyaluronic acid and type Ⅳ collagen in the two groups showed an upward trend with significant difference (P<0.05). After 1 day of treatment, the serum levels of MMP-9 and TIMP1 in the observation group reached a peak, then gradually decreased, with significant difference (P<0.05). The incidence of ALI/ARDS in the observation group and the control group (11.9% vs 31.0%) and the duration of ICU treatment [(10.2±3.2)d vs (13.2±2.8)d].@*Conclusions@#For patients with acute paraquat poisoning, the combination of anisodamine and blood purification can down-regulate the expressions of MMP-9 and TIMP1 and delay the progression of pulmonary fibrosis, thus improving the clinical therapeutic effect.

Protein expressions of matrix metalloproteinase-9 and its inhibitor and their ratio changes in wound healing of patients with stages Ⅲ and Ⅳ pressure ulcers / 中华烧伤杂志

Objective@#To explore the expression levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein and the change of MMP-9/TIMP-1 ratio in wound exudates of patients with stages Ⅲ and Ⅳ pressure ulcers during wound healing.@*Methods@#From July 2017 to July 2018, 30 patients with stage Ⅲ pressure ulcers [30 wounds, 16 males and 14 females, aged (65±10) years] and 34 patients with stage Ⅳ pressure ulcers [50 wounds, 17 males and 17 females, aged (65±9) years] admitted to Hebei General Hospital who met the inclusion criteria were enrolled in this prospective cohort study. According to the principle of wound treatment and the characteristics and needs of wound in different periods, individualized intervention measures were formulated for patients and appropriate dressings were selected. At the time of admission and on 7, 14, 21, 28 days of treatment, the healing of pressure ulcer wounds was evaluated by Pressure Ulcer Healing Scale. Afterwards, the wound exudate was collected at each time point to detect the expression levels of MMP-9 and TIMP-1 protein by enzyme-linked immunosorbent assay, and the MMP-9/TIMP-1 ratio was calculated. Data were processed with analysis of variance for repeated measurements of single group and linear trend test.@*Results@#(1) There were significantly statistical differences in wound healing scores of patients with stages Ⅲ and Ⅳ pressure ulcers among the time of admission and on 7, 14, 21, 28 days of treatment within each stage (F=145.382, 153.234, P<0.01), and they all showed a gradually decreasing trend (F=170.466, 284.585, P<0.01). (2) At the time of admission and on 7, 14, 21, 28 days of treatment, the expression levels of MMP-9 protein in wound exudates of patients with stages Ⅲ and Ⅳ pressure ulcers were (171±104), (138±88), (110±70), (85±55), (62±41) ng/L and (193±107), (173±104), (139±83), (114±70), (89±56) ng/L, respectively. There were significantly statistical differences within each stage (F=58.007, 111.680, P<0.01), and they all showed a gradually decreasing trend (F=62.901, 134.628, P<0.01). At the time of admission and on 7, 14, 21, 28 days of treatment, the expression levels of TIMP-1 protein in wound exudates of patients with stages Ⅲ and Ⅳ pressure ulcers were (6.2±3.9), (5.6±3.4), (5.1±3.1), (4.4±2.5), (3.8±2.3) ng/L and (4.8±2.5), (4.7±2.6), (4.4±2.6), (4.6±2.7), (4.1±2.4) ng/L, respectively. There were significantly statistical differences within each stage (F=25.479, 7.778, P<0.01), and there was a gradually decreasing trend in stage Ⅲ (F=62.901, P<0.01) and a decreasing trend in stage Ⅳ (F=134.628, P<0.01). At the time of admission, the expression levels of MMP-9 and TIMP-1 in wound exudates of patients with stage Ⅲ pressure ulcers were similar to those of patients with stage Ⅳ pressure ulcers (t=-1.03, 1.47, P>0.05). (3) At the time of admission and on 7, 14, 21, 28 days of treatment, the MMP-9/TIMP-1 ratios in the wound exudates of patients with pressure ulcers of stages Ⅲ and Ⅳ were 30±13, 25±9, 22±9, 20±8, 17±6 and 43±19, 37±13, 32±10, 26±9, 22±9, respectively. There were significantly statistical differences within each stage (F=37.173, 97.191, P<0.01), and they all showed a gradually decreasing trend (F=54.183, 130.088, P<0.01). At the time of admission, the MMP-9/TIMP-1 ratio in wound exudates of patients with stage Ⅳ pressure ulcers was significantly higher than that of patients with stage Ⅲ pressure ulcers (t=-3.42, P<0.01).@*Conclusions@#During the wound healing process of patients with stages Ⅲ and Ⅳ pressure ulcers, the expression levels of MMP-9 and TIMP-1 protein and the MMP-9/TIMP-1 ratio in wound exudates show a decreasing trend. The stage of wound healing can be predicted according to the expression level of MMP-9 protein and the MMP-9/TIMP-1 ratio.

Effect of anisodamine combined with blood purification on pulmonary fibrosis, serum matrix metalloproteinase-9 and matrix metalloproteinase 1 levels in patients with paraquat poisoning / 中国医师杂志

Objective To investigate the effect of anisodamine combined with blood purification on pulmonary fibrosis and levels of serum matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase 1 (TIMP1) in patients with paraquat poisoning.Methods From March 2013 to February 2017,84 patients with paraquat poisoning admitted to our hospital were enrolled in the observation group (anisodamine +blood purification) or control group (blood purification),42 cases in each group.The curative effect,indexes related to pulmonary fibrosis,serum MMP-9 and TIMP1 levels were compared between the two groups.The incidence of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and intensive care uni (ICU) admission time were recorded.Results There was significant difference (P ＜ 0.05) in the total effective rate (88.1％ vs 69.0％) and the high-resolution computed tomography (CT) score after 7 days of treatment (8.4 ± 0.9 vs 12.3 ± 1.4) between the observation group and the control group.At the same time,the serum levels of hyaluronic acid and type Ⅳ collagen in the two groups showed an upward trend with significant difference (P ＜ 0.05).After 1 day of treatment,the serum levels of MMP-9 and TIMP1 in the observation group reached a peak,then gradually decreased,with significant difference (P ＜0.05).The incidence of ALI/ARDS in the observation group and the control group (11.9％ vs 31.0％)and the duration of ICU treatment [(10.2 ± 3.2) d vs (13.2 ± 2.8) d].Conclusions For patients with acute paraquat poisoning,the combination of anisodamine and blood purification can down-regulate the expressions of MMP-9 and TIMP1 and delay the progression of pulmonary fibrosis,thus improving the clinical therapeutic effect.

Effect of electroacupuncture on renal fibrosis in spontaneously hypertension rats and its related mechanisms / 针刺研究

OBJECTIVE: To observe the effect of electroacupuncture (EA) on blood pressure, renal fibrosis and expression of tissue inhibitors of metalloproteinase-1 (TIMP-1), plasminogen activator inhibitor 1 (PAI-1), and alpha smooth muscle actin (α-SMA) in spontaneous hypertension rats (SHR), so as to explore its mechanisms underlying improving hypertensive renal damage. METHODS: Forty male SHR (15 weeks in age) were randomly divided into 5 groups: model, medication (Losartan), Shenshu, Geshu, and Shenshu＋Geshu groups(n=8 rats in each group), and the same age-old male 8 Wistar-Kyoto (WKY) rats were used as the normal control group. Rats of the medication group were treated by gavage of Losartan potassium solution (3 mg/mL, 30 mg·kg-1·d-1, once a day for 12 weeks), and those of the 3 EA groups treated by EA stimulation of bilateral "Shenshu" (BL23), "Geshu"(BL17) or both BL23 and BL17 (2 Hz/100 Hz, 1 mA, 15 min each time, once every other day for 12 weeks). The systolic blood pressure of the tail artery was measured before, and 4, 8 and 12 weeks after the intervention. The expression of TIMP-1, PAI-1 and α-SMA proteins of the right kidney tissue was measured by immunohistochemistry. Histopathological changes of the right renal tissue were observed under light microscope after H.E. stain. RESULTS: The blood pressure was significantly higher in the mo-del group than those in the normal control group (P<0.01), and considerably decreased at the 4th , 8th, and 12th week of the interventions in the medication and 3 EA groups (P<0.01). The expression levels of renal TIMP-1, PAI-1 and α-SMA proteins were notably higher in the model group than those in the normal control group and considerably decreased at the 12th week of the interventions in the medication and 3 EA groups than in the model group (P<0.01). H.E. staining of the renal tissue showed disordered arrangement of the renal cells, congestion and dilation of capillaries with thickened vascular wall, renal tubule atrophy and lumen stenosis with some necrosis of renal tubules, protein tubule and cell tubules, increase of some glomerular mesangial matrix and hyperplasia of fibrous tissue in the model group, which was re-latively milder in the medication and 3 EA groups. CONCLUSION: EA of BL23 and BL17 can reduce the blood pressure in SHR, which may be related to its function in down-regulating expression of TIMP-1, PAI-1 and α-SMA proteins.

Effect of 3D-CRT combined with PC chemotherapy on non-small cell lung cancer patients and serum CA125,TIMP-1,SAA levels and immune function / 国际肿瘤学杂志

Objective To investigate the effect of three-dimensional conformal radiotherapy (3D-CRT)combined with PC chemotherapy (paclitaxel + carboplatin)on non-small cell lung cancer (NSCLC) patients and the serum levels of CA125,tissue inhibitor of metalloproteinase-1 (TIMP-1),serum amyloid A (SAA)and T-lymphocyte subsets. Methods A total of 100 patients with NSCLC treated in Affiliated Hospital of Guangdong Medical University from May 2015 to December 2017 were selected as the study subjects. They were divided into control group and observation group according to random number table method,with 50 cases in each group. The observation group was treated with 3D-CRT combined with PC chemotherapy,while the con-trol group was treated with PC chemotherapy. The two groups were treated for 4 cycles. The therapeutic effect, serum CA125,TIMP-1,SAA,T-lymphocyte subsets and adverse reactions were compared between the two groups. Results Four cases were lost to follow-up both in the two groups. The overall response rate in the observation group (43. 48％,20 / 46)was higher than that in the control group (23. 91％,11 / 46;χ2 = 3. 941, P = 0. 047). The serum levels of CA125,TIMP-1 and SAA of the two groups had no significant difference be-fore treatment,and the levels of these indexes decreased after treatment. The serum levels of CA125,TIMP-1 and SAA in the observation group after treatment were (12. 31 ± 1. 13)U/ ml,(275. 31 ± 13. 69)pg/ ml and (47. 21 ± 7. 21)mg/ L,which were lower than those in the control group [(30. 36 ± 1. 98)U/ ml,(320. 36 ± 17. 23)pg/ ml,(65. 92 ± 8. 36)mg/ L],with significant differences (t = 53. 699,P < 0. 001;t = 13. 884, P < 0. 001;t = 11. 495,P < 0. 001). The levels of CD3 +,CD4 +,CD8 + and CD4 + / CD8 + of the two groups had no significant difference before treatment,and the levels of these indexes decreased after treatment. The levels of CD3 +,CD4 +,CD8 + and CD4 + / CD8 + in the observation group were (35. 27 ± 10. 31 )％, (20. 27 ± 6. 72)％,(15. 89 ± 3. 37)％ and 0. 91 ± 0. 37,which were higher than those in the control group [(30. 77 ± 9. 27)％,(15. 27 ± 5. 73)％,(12. 02 ± 2. 69)％ and 0. 75 ± 0. 39],with significant differences (t = 2. 201,P = 0. 030;t = 3. 840,P < 0. 001;t = 6. 087,P < 0. 001;t = 2. 019,P = 0. 047). There were no significant differences in the adverse reactions such as nausea and vomiting [63. 04％ (29 / 46)vs. 43. 48％(20 / 46);χ2 = 3. 537,P = 0. 060],phlebitis [6. 52％ (3 / 46)vs. 4. 35％ (2 / 46);χ2 = 0. 000,P >0. 999],abnormal liver function [6. 52％ (3 / 46)vs. 2. 17％ (1 / 46);χ2 = 0. 261,P = 0. 609]and myelo-suppression [8. 70％ (4 / 46)vs. 6. 52％ (3 / 46);χ2 = 0. 000,P > 0. 999]between the observation group and the control group. Conclusion For patients with NSCLC,3D-CRT combined with PC chemotherapy can im-prove the overall response rate,decrease the levels of serum CA125,TIMP-1 and SAA,and improve the im-mune function of patients. The therapeutic effect is remarkable and the safety is good. The therapeutic scheme is suitable for the treatment of NSCLC.