BACKGROUND:It is particularly important to establish an ideal animal model of pulmonary fibrosis to investigate the underlying pathogenesis and screen effective drugs to prevent and control pulmonary fibrosis. OBJECTIVE: To establish a modified scheme of establishing mouse models that can reflect pulmonary fibrosis formation in humans. METHODS: Fifty-six male C57BL/6 mice were randomly divided into two groups: A (a single large-dose injection) and B (multiple smal-dose injections). Mice in group A were subjected to a single intravenous injection of bleomycin 200 mg/kgviathe tail vein; and mice in group B received intravenous injections of bleomycin 50 mg/kg via the tail vein per week, totaly for 6 weeks. 

BACKGROUND:There is no effective drug for idiopathic pulmonary fibrosis (IPF), because of a lack of the animal model imitating the complete pathogenesis of human IPF. Therefore, it is critical to establish an ideal animal IPF model used for investigating the underlying pathogenesis and developing a kind of effective drug. OBJECTIVE:To establish an animal model that can mimic more characters of human IPF. METHODS:Seventy male C57BL/6 mice were randomly divided into two groups, fol owed by subjected to the intraperitoneal injection of bleomycin (35 mg/kg) on days 1, 4, 8, 11, 15, 18, 22, and 25, twice (group A) or once (group B) a week. Mice were sacrificed at 2, 4, 6, 8, and 10 weeks after the eighth injection, and the lung tissues were moved used for hematoxylin-eosin, Masson and immunohistochemical stainings. RESULTS AND CONCLUSION:There were various degrees of alveolitis and pulmonary fibrosis in the two groups at different time points after the last injection. The scores of alveolitis and pulmonary fibrosis in the group A began to gradual y increase from the 2nd week and reached the highest level at the 6th-8th weeks until the 10th week. In contrast, the scores of alveolitis and pulmonary fibrosis in the group B peaked at the 2nd week, then fluctuately decreased, and were significantly lower than those in the group A at the 6th week (P<0.05). Immunohistochemistry showed that type I col agen deposition was mainly distributed in the subpleural region, peri-vascular region and alveolar septa, which was consistent with Masson staining findings. The expression levels of transforming growth factorβ1 (TGF-β1) andα-smooth muscle actin (α-SMA) in the regions developing alveolitis and pulmonary fibrosis were significantly increased. In the group A, the expression levels of type I col agen, TGF-β1,α-SMA, and the hydroxyproline content in the lung tissues reached the peak level at 6-8 weeks. However, in the group B, al above indicators reached the highest level at the 2nd week, but gradual y decreased thereafter. At the 4th week, the expression Levels of TGF-β1 andα-SMA in the group B were significantly lower than those in the group A (P<0.05). At the 6th week, the hydroxyproline and type I col agen levels in the group B were significantly lower than those in the group A (P<0.05). In conclusion, the mouse model of pulmonary fibrosis induced by intraperitoneal injection of 35 mg/kg bleomycin twice weekly can be used to mimic the repetitive wound healing process, pathological morphology and cytokine changes of human IPF, which is prone to administration, with better stability and repeatability. This model is of great significance for the study on IPF. Subject headings:Disease Models, Animal;Pulmonary Fibrosis;Bleomycin

Objective To study if IRF1 could regulate the polarization by IRF 1 and M1 status and affect M1 media-ted antitumor function .Methods U937 derived M1 macrophage ( U937-M1 ) model was established .The cells were devided into 4 groups:the PMA pretreated unpolarized macrophage (M0), the PMA, IFN-γand LPS induced M1 macrophage (M1), the siRNA of IRF1 knocked down M1 macrophage (siIRF1) and the negative control siR-NA treated M1 macrophage (siC).Furthermore, the expression of CD86 and CD206 was detected by flow cytome-try, the M1/M2 associated markers (IL-12p35,IL-12p40,IL-23p19,IL-6,TNF-α/IL-10) and IFNB1 were ana-lyzed by qPCR,the expression of IL-12p70 and IL-10 was examined by ELISA, the expression of IRF1 and IRF5 was detected by Western blot , the proliferration and apoptosis of HCC were analyzed by CCK 8 and flow cytometry , respectively.Results Compared with the U937-M1, the IRF1 knocked down group showed impaired CD 86 expres-sion, but enhanced CD206 expreesion ( P<0.05 ); the expression of M1 related cytokines including IL-12p35, IL-12p40,IL-23p19,IL-6,TNF-αand IFNB1 was decreased, but M2 related cytokine IL-10 level was increased (P<0.01);the expression of IFN-β, IL-12p70 and IRF5 was impaired, but IL-10 was enhanced (P<0.05).In IRF1 knocked down U937-M1, the CCK8 analysis indicated that the M1 mediated anti-proliferation effects on hepatoma carcinoma cell were turned to pro-proliferation ( P<0.05);the flow cytometry showed that the M 1 mediated pro-ap-optosis effects were reversed to anti-apoptosis ( P<0.01 ) .Interestingly , IRF5 and IFN-βwere decreased at both mRNA and protein levels in IRF1 knocked down U937-M1 compared with the U937-M1 (P<0.01).Conclusions IRF1 may partly modulate IRF5 and IFN-β, and further regulate M1 polarization and its antitumor effects .

This study retrospectively analyzed the clinical data of 1 case of spermatic cord leiomyosarcoma admitted to the urology department of the Affiliated Hospital of Chengde Medical College. The clinical characteristics, diagnosis, treatment and prognosis was discussed with the literature review. Radical resection of the left testicle and high ligation of the left spermatic cord were performed. Postoperative pathology was spermatic cord leiomyosarcoma. Its clinical manifestations are painless masses, which are mainly confirmed by pathological examination. The treatment is mainly radical resection, and postoperative radiotherapy can improve the prognosis and reduce recurrence.