Objective To explore the inhibitory mechanism of Imatinib mesylate on pulmonary fibrosis induced by bleomycin inmice. Methods A total of 120 C57BL/6 mice were randomly divided into four groups, ie. a control group, a model group, a dexamethasone group, and an Imatinib group. The model of pulmonary fibrosis was established by a single intratracheal instillation of bleomycin in the rats. Then dexamethasone or Imatinib were given intraperitoneally respectively. On day 7, 14, 21 after the treatment, 10 mice of each group were sacrificed respectively. The expressions of TGF-β1 and α-SMA in lung tissue were analyzed by immunohistochemistry. The mRNA expression of TGF-β1 was measured by RT-PCR. Results The expressions of TGF-β1 and α-SMA in lung tissue at each time point were significantly increased in the model group compared with the control group. And the expressions were obviously decreased in the dexamethasone group and the Imatinib group compared with the model group, with no significant differences between the two treatment groups. The expression of TGF-β1 was positively correlated with the α-SMA expression ( r= 0. 251, P lt;0. 05) . Conclusion The inhibitory effect of Imatinib on pulmonary fibrosis may be related to the inhibition of TGF-β1 and α-SMA expressions.
Objective To improve the awareness of acute exacerbation of idiopathic pulmonary fibrosis ( AEIPF) and discuss its clinical characteristics, diagnosis, treatment and outcome. Methods The clinical data of patients with AEIPF from June 2006 to June 2011 in 11 hospitals in Jiangsu were collected and analyzed. Resluts There were 18 males and 3 females in the AEIPF patients with mean age of ( 67.4 ± 8.1) years. The duration from IPF diagnosis was ( 7.4 ±8.2) months. The duration of acute symptom before admission was ( 7.0 ±5.3) days. The distribution pattern of new groud-glass opacity was peripheral in 3 patients,multifocal in 5 patients, and diffuse in13 patients. All patients were treated with corticosteroid pulse therapy. Nine patients survived and 12 patients died. The mortality rate was 57.1% . Conclusions AEIPF progresses quickly and the mortality rate is very high. Corticosteroid pulse therapy is the mainstay of therapy in AEIPF patients.
ObjectiveTo systematically review the diagnostic value of FibroScan for the staging of liver fibrosis in chronic hepatitis B. MethodsWe searched the PubMed, EMbase, Web of Knowledge, CBM, WanFang Data and CNKI databases for studies investigated the diagnostic value of FibroScan for hepatic fibrosis B from Jan. 1st, 2003 to Aug. 31st, 2013. Two reviewers independently screened literature according to the exclusion and inclusion criteria, extracted data and assessed methodological quality of included studies. Then, Stata 13.0 software was used to analyze the data. ResultsA total of 15 studies involving 2 588 patients were included. The results of meta-analysis showed that:the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the AUC of SROC were 0.77 (95%CI 0.69 to 0.83), 0.84 (95%CI 0.70 to 0.87), 3.8 (95%CI 2.6 to 5.6), 0.29 (95%CI 0.22 to 0.38), 13 (95%CI 8 to 21), 0.82 (95%CI 0.82 to 0.88) for hepatic fibrosis; and were 0.81 (95%CI 0.73 to 0.87), 0.89 (95%CI 0.86 to 0.92), 7.5 (95%CI 5.3 to 10.3), 0.21 (95%CI 0.14 to 0.31), 36 (95%CI 20 to 65), 0.93 (95%CI 0.90 to 0.95) for early hepatic cirrhosis, respectively. ConclusionThe current evidence suggests that FibroScan is of good accuracy in the diagnosis of early hepatic fibrosis but not for hepatic cirrhosis in patient with chronic hepatitis B.
ObjectiveTo summarize the pathogenesis, epidemiology, and risk factors of portal vein thrombosis after splenectomy, and combined with the latest advances in clinical prevention, diagnosis, and treatment of portal vein thrombosis after splenectomy, so as to provide some references for clinical prevention and treatment in the future.MethodLiteratures on portal vein thrombosis after splenectomy were collected and reviewed.ResultsThe incidence of portal vein thrombosis after splenectomy was high and its occurrence was the result of multiple factors. It was mainly related to the change of splenic venous blood flow mechanics after splenectomy. In terms of diagnosis, enhanced CT scan was the first choice. Currently, there was no consensus on treatment options, which mainly focused on individualized treatment and emphasized that preventive anticoagulant use of low-molecular-weight heparin may reduce the risk of portal vein thrombosis.ConclusionThe concept of tertiary prevention of portal vein thrombosis after splenectomy should be established, and individualized treatment should be adopted in combination with the patient’s condition.
Objective To study the pathology and possible mechanism of experimental hydrochloric acid（HCl） inhalation-indued pulmonary fibrosis in rats.Methods 120 male SD rats were randomly divided into a nomal control group，a bleomycin group，a high dose HCl group，a middle dose HCl group and a low dose HCl group.The bleomycin group was intratracheally injected with bleomycin once to induce pulmonary fibrosis.The three HCl groups were intratracheally injected with HCl once per week.The control group was given saline by the same way.Six rats of each group were randomly sacrificed on day 7，14，28 and 42 respectively.The histological changes of lung tissue were studied by HE and Masson’s trichrome staining.Hydroxyproline level in lung tissue was measured by digestion method.Protein and mRNA expression of transforming growth factor-β1（TGF-β1） were assayed by immunohistochemistry and RT-PCR respectively.Results Alveolitis in three HCl groups was significantl compared to control group，most severe at the second week，then remained at a high level which was equivalent to or exceeded the level of the bleomysin group after 28 days.Pulmonary fibrosis in three HCl groups was also significantly more severe than that in the control group，but milder than that in the bleomysin group.The high-dose and middle-dose HCl groups were not significantly different from the bleomysin group on day 42.There was no difference between three HCl groups in the earlier period，but the high-dose HCl group has a significantly difference from low-dose group on day 42.The content of hydroxyproline in high-dose and middle-dose HCl groups was also significantly higher than that in the control group.On day 42 hydroxyproline content in high-dose HCl dose rather middle –or low dose group was similiar with the level of bleomysin group.Content of TGF-β1 mRNA in three HCl groups was comparable to the level of bleomysin group on day 28 and exceeded on day 42.The expression of TGF-β1 in three HCl groups was not significantly different from the bleomysin group on day 42.Conclusion Experimental acid aspiration might contribute to pulmonary fibrosis in rats.Acid induced alveolar epithelial cell damage，abnormal proliferation and repair and fibrosis could be involved..
Trying to provide ultrasonic image-aid measures for quantitative diagnosis and dynamic monitoring of liver fibrosis, we propose two scoring methods for liver fibrosis tissue in vivo, based on ultrasound radio frequency (RF) time series in this paper. Firstly, RF echo signals of human liver were recorded in this study. Then one of the recorded frame RF data was demodulated to be B model image. After that, a region of interest (ROI) in the B model image was selected. For each point in the ROI, its all frame data were acquired so that RF time series were formed. An SMR (size measure relationship) fractal dimension and six spectral features were extracted from RF time series in the ROI. With relative deviation and Fisher's discriminant ratio, seven features were weighted and summed so that the liver tissues' scores were obtained, Score-rd and Score-fisher, respectively. Area under ROC curve (AUC) and a support vector machine (SVM) were used to evaluate whether these scoring methods would be useful in distinguishing normal and cirrhosis tissues. Experimental results are shown as follows: Score-rd's AUC was 0.843, while Score-fisher was 0.816, SVM classification accuracies were both up to 87.5%. This proved that our proposed scoring methods were effective in distinguishing normal and cirrhosis tissues. Score-rd and Score-fisher have potential for clinical applications. They can also provide quantitative references for liver fibrosis diagnosis.
Objective To find a new specific marker that can be used to early diagnose hepatic fibrosis by detecting the change of serum protein in patients with hepatic fibrosis. Methods This research adopted 50 SD rats (25 males and 25 females), and from which 6 rats were selected randomly (3 males and 3 females) as control group, last 44 rates were divided into four groups according to four pathological stages as hepatic fibrosis model group (experimental group). Distinct proteins in serum were detected by surface-enhanced laser desorption/ionization-time of flight-mass spectra (SELDI-TOF-MS). Radioimmunoassay was used to measure four parameters of hepatic fibrosis which were hyaluronidase (HA), precollagen Ⅲ (PCⅢ), laminin (LN) and collagen Ⅳ (Ⅳ-C). Results Distinct proteins in serum were detected in 8 cases of stage Ⅰ of hapatic fibrosis, 5 cases of stage Ⅱ, 5 cases of stage Ⅲ, 6 cases of stage Ⅳ, and 5 cases of control by SELDI-TOF-MS. Three protein peaks were found (M/Z: 4 203, 4 658, and 7 400). The peaks of M/Z 4 658 and 4 700 proteins were obviously increased in the stage Ⅰ of hepatic fibrosis （Plt;0.05）, while the changes of hepatic fibrosis four parameters appeared in stage Ⅳ of hepatic fibrosis. Conclusion This method shows great potential for early diagnosing of hepatic fibrosis and finding better biomarkers to hepatic fibrosis.
Objective To explore whether epithelial to mesenchymal transition ( EMT) occurs in bleomycin( BLM) induced pulmonary fibrosis, and the involvement of bronchial epithelial cells( BECs) in the EMT. Methods BLM-induced peribronchial fibrosis in an α-smooth muscle actin-Cre transgenic mouse( α-SMACre /R26R) was examined by pulmonary βgal staining and α-SMA immunofluorescence staining. Results BLMtreated mice showed significantly enhanced βgal staining in subepithelial areas in bronchi, terminal bronchioles and walls of pulmonary vessels. Some alveolar epithelial cells( AECs) in certain peribronchial areas or even a small subset of BECs were also positively stained, as confirmed by α-SMA immunostaining. Conclusions EMT occurs in BLM-induced peribronchial fibrosis mice. BECs, like AECs, have the capacity to undergo EMT and to contribute to mesenchymal expansion in pulmonary fibrosis.
Objective To review research progress of pancreas stellate cells in pancreas fibrosis and understand characteristics and activation of pancreas stellate cells and its mechanism on pancreas fibrosis. Method The relevant literatures about pancreas stellate cells and its studies in pancreas fibrosis were reviewed. Results The activation of pancreatic stellate cell is associated with fibrosis of pancreatitis and end stage of pancreas transplantation, but its effect and regulation mechanisms for the extracelluar and intracellular molecular network need to be further investigated. Conclusion Elucidation of activation of pancreas stellate cells will facilitate understanding of pancreas fibrosis and searching new target in treatment of pancreas fibrosis.
Objective To investigate the expression of fibroblast activation protein( FAP) in mouse pulmonary fibrosis and the relationship between FAP and trarisforming growth factor β1 ( TGF-β1 ) .Methods The mouse model with pulmonary fibrosis was established by intratracheally instillation of bleomycin. The expressions of FAP, α-smooth muscle action( α-SMA) , and TGF-β1 in lung tissues were detected with immunohistochemical technique. Results There was no expression of FAP in the normal lung tissue. In the pulmonary fibrosis mice, FAP was found in the fibroblasts existed in bronchiolar adventitia or peribronchiolar ( and perivascular) connective tissue. In the fibroblast foci, the localizations of α-SMA, TGF-β1 , and FAP were similar, but the expression of FAP was more extensive than that of α-SMA and ber than that ofTGF-β1 . The degree of lung fibrosis was bly correlated with FAP, α-SMA, and TGF-β1 ( r = 0. 795,0. 766,0. 628; P lt; 0. 01) . A significantly positive correlation was also observed between TGF-β1 and FAP( r =0. 706, P lt; 0. 01) . Conclusions FAP is especially expressed in the fibroblast foci in pulmonaryfibrosis and bly correlated with the severity of pulmonary fibrosis. FAP and TGF-β1 possibly play a synergistic role in the progression of pulmonary fibrosis.