ObjectiveTo explore the antioxidant effects of reduced glutathione on rat pulmonary fibrosis compared with traditional corticosteroid. MethodsOne-hundred and eight healthy SD rats were randomly divided into 6 groups,ie. a control group,a model group,a dexamethasone group,a low-dose glutathione group,a middle-dose glutathione group,and a high-dose glutathione group,with 18 rats in each group. The pulmonary fibrosis model was established by intratrachially instillation of bleomycin in all rats except the control group. The severity of lung fibrosis was evaluated by HE staining and Masson staining of collagen,and measurement of glutathione,hydroxyproline,superoxide dismutase (SOD),glutathion peroxidase (GSH-Px)in lung tissue homogenate by photocolorimetric method. ResultsOn 7th day and 14th day after bleomycin instillation, the severity of alveolitis in the model group,the dexamethasone group,and three glutathione intervention groups was significantly reduced compared with the control group (P<0.05). On 28 day, the severity of lung fibrosis was significantly reduced in the dexamethasone group and three glutathione intervention groups compared with the model group (P<0.05). On 7th day,lung glutathione content was significantly lower in the model group compared with the control group (P<0.05), significantly higher in the dexamethasone group and three glutathione intervention groups compared with the model group (P<0.05), significantly lower in the dexamethasone group and the low-dose glutathione group compared with the control group (P<0.05), and significantly higher in the high-dose glutathione group compared with the dexamethasone group (P<0.05). On 7th,14th,and 28th day,the hydroxyproline content in the dexamethasone group and three glutathione intervention groups decreased significantly compared with the model group (P<0.05). On 14th day,the hydroxyproline content in the middle-dose and high-dose glutathione groups was significantly lower than that in the dexamethasone group (P<0.05). SOD and GSH-Px were significantly reduced in the model group compared with the control group on all time points (P<0.05),but significantly increased after intervention by different doses of glutathione (P<0.05). ConclusionReduced glutathione can significantly reduce the degree of pulmonary fibrosis in rats,but has no obvious advantage over dexamethasone.
Objectives To systematically review the association between TM6SF2 (transmembrane six superfamily member 2- rs58592426) polymorphism and liver lesion and the severity of liver fibrosis. Methods We electronically searched databases including PubMed, CNKI, WanFang Data and CBM from inception to January 27, 2016, to collect cross-sectional studies about the association between the TM6SF2 polymorphism and the liver lesion and the severity of liver fibrosis. Two reviewers independently screened literature, extracted data and assessed the methodological quality included studies. Then, meta-analysis was performed using Stata 12.0 software. Results A total of 23 studies including 96 594 patients were included. The results of meta-analysis showed that: TM6SF2 polymorphism was associated with increased risk of the severity of liver fibrosis, the levels of TG, TC and LDL-C (all P values < 0.05). Carriers of the T allele showed lower levels of TG, TC, and LDL-C. Carriers of the T allele revealed higher levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) when compared with homozygous EE. Conclusion TM6SF2 polymorphism is associated with lipid traits in different population, the variants shows lower levels of lipid traits in blood serum and increases the risk of the severity of liver fibrosis and liver lesion.
Objective To investigate the effects of sodium ferulate on lung mRNA expression of TGF-β1 signal transduction molecule in rats with pulmonary fibrosis，and explore the mechanism of sodium ferulate on pulmonary fibrosis.Methods A rat model of pulmonary fibrosis was induced by intratracheal injection of bleomycin (5 mg/kg).Thirty SD rats were randomly divided into three groups (n=10 in each group)，ie.a control group，a pulmonary fibrosis model group，and a sodium ferulate group.The lung histopathology and the expression of collagen was examined by HE staining and collagen fibril staining respectively.The expressions of TGF-βRII and Smad4 mRNA in the lung tissue were detected by situ hybridization.And the expression of TGF-β1 mRNA was detected by real-time fluorescence-quantification RT-PCR.Results Collagen fibril staining indicated that the expression of pulmonary collagen in the model group was significantly higher than that in the control group and sodium ferulate group (Plt;0.001).The mRNA expressions of pulmonary TGF-β1，TGF-βRII and Smad4 were significantly higher in the model group than those in the control group (all Plt;0.01)，and were significantly lower in the sodium ferulate group than those in the model group (all Plt;0.05).Conclusions Sodium ferulate can effectively reduce pulmonary fibrosis through inhibition of the mRNA expression of TGF-β1，TGF-βRII and Smad4 in the lung tissue，thus influence the TGF-β1/Smad4 signal transduction way and inhibit the target gene activation.
Objective To explore the prognostic significance of baseline clinical and pulmonary physiological variables on idiopathic pulmonary fibrosis ( IPF) . Methods Patients diagnosed with IPF according to 2011 ATS/ERS/JRS/ALAT statementwere selected from Nanjing DrumTower Hospital between January 1, 2002 and July 31, 2010. The baseline characteristics were abstracted, including age, gender, smoking history, corticosteroid, delay before diagnosis, body mass index, finger clubbing, oxygenation index ( PaO2 /FiO2 ) , C-reaction protein, erythrocyte sedimentation rate ( ESR) , serum lactate dehydrogenase ( LDH) , albumin, vital capacity ( VC) , forced vital capacity ( FVC) , total lung capacity ( TLC) , and singlebreath diffusing capacity of the lung for carbon monoxide ( DLCO) . The relationships between all factors and survival were examined with a univariate Cox proportional-hazard model. Kaplan-Meier method was used to assess the survival probabilities between groups with different baseline characteristics. Results Eighty-four patients were included in this study, with the median survival time of 34. 7 months. PaO2 /FiO2 , FVC% pred, VC% pred, TLC% pred, and DLCO% pred showed significant associations with the mortality of IPF ( hazard ratios 0. 940-0. 994, P lt; 0. 01) . The Kaplan-Meier analyses for above variables also showed significant differences ( P lt;0. 05) . Besides, the statistical difference of survival probability could be found between the patients with elevated serumLDH and those with normal LDH ( 27. 0 months vs. 43. 1 months, P =0. 014) . Conclusions Baseline oxygenation and pulmonary function parameters may indicate the prognosis of IPF patients. Serum LDH may provide clinicians with additional prognostic information.
ObjectivesTo systematically review the efficacy and safety of ciprofloxacin for non-cystic fibrosis bronchiectasis.MethodsDatabases including PubMed, EMbase, The Cochrane Library, CBM, VIP, CNKI and WanFang Data were electronically searched from inception to August 2018 to collect randomized controlled trials (RCTs) on ciprofloxacin in the treatment of non-cystic fibrosis bronchiectasis. Two reviewers independently screened literature, extracted data, and assessed risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 9 RCTs involving 1 666 patients were included. The results of meta-analysis showed that: compared with control group, the ciprofloxacin more efficiently eradicate bacteria from sputum (RR=4.34, 95%CI 2.04 to 9.23, P=0.000 1), decrease risk of the exacerbations (RR=0.81, 95%CI 0.71 to 0.93, P=0.002) and the mean bacterial load (MD=–4.08, 95%CI –6.29 to –1.87, P=0.001). However, there were no significant differences between two groups in clinical efficiency and adverse events.ConclusionsThe current evidence shows that, ciprofloxacin can decrease the mean bacterial load and risk of the exacerbation, and more efficiently eradicate bacteria from sputum in non-cystic fibrosis bronchiectasis patients. Due to limited quality and quantity of the included studies, more studies are required to verify the conclusions.
Objective To establish a mouse model of acute lung injury ( ALI) and pulmonary fibrosis by low dose lipopolysaccharide ( LPS) intermittent intraperitoneal injection, and to explore the pathogenesis of ALI and pulmonary fibrosis induced by endotoxin. Methods Forty C57BL/6 mice were randomly divided into a control group, a 3-days LPS group, a 2-weeks LPS group, and a 4-weeks LPS group,with 10 mice in each group. LPS was injected intraperitoneally at dose of 5 mg/ kg for three consecutive daysin the three LPS groups. Equivalent normal saline was injected by the same way in the control group. The mice lung tissues were obtained respectively 3 days ( the control group and 3-days LPS group) , 2 weeks ( the 2-weeks LPS group) , and 4 weeks ( the 4-weeks LPS group) after LPS or saline stimulation. HE staining,Van-Gieson collagen staining, and Ashcroft fibrosis score assessment were applied to evaluate the development of inflammation and fibrosis in lung tissue at various stages of ALI after LPS-stimulation. The mRNA expression of type Ⅰ procollagen and alpha smooth muscle actin ( α-SMA) were detected by realtime PCR. The deposition of collagen and fibrosis in lung tissue were detected by hydroxyproline assay. The survival condition of each group was also recorded. Results Acute inflammation occurred in mice lung tissue 3 days after intraperitoneal injection of LPS. Collagen deposited in pulmonary interstitium2 weeks afterLPS-stimulation and formed typical pulmonary interstitial fibrosis 4 weeks later accompanying with increase of Ashcroft fibrosis score. Real-time PCR and hydroxyproline assay showed that the expression of collagen and α-SMA increased 3 days after LPS-stimulation and reached the peak 4 weeks later. The animals were all survived up to the endpoint of experiment. Conclusions Accompanying with inflammation, pulmonary fibrosis initiated at early stage of ALI induced by LPS. Intraperitoneal injection of LPS at dose of 5 mg/kg for three consecutive days was able to establish the mouse model of ALI and pulmonary fibrosis with high successrate and low animal mortality, which provide an ideal experimental platform for further investigation.
Objective To explore the migration and differentiation of bone marrow mesenchymal stem cells（MSCs） in lung . Methods MSCs were harvested from a male Wister rat. Sixty female Wister rats were randomly divided into four groups. The pulmonary fibrosis model was established by intratracheal instillation of bleomycin in group A-D. Immediately and 7 days after bleomycin administration respectively，the rats in group B and C received infusion with 5-bromodeoxynridine （BrdU） labeled MSCs via tail vein. And the rats in group D were infused MSCs without BrdU labeling serving as a negative control. The sry gene of Y chromosome was detected by polymerase chain reaction （PCR）. Double immunofluorescence staining was used to detected BrdU and surfactant associated protein-C （SP-C） expression in lung tissue，fresh bone marrow，and the 5th generation MSCs. Reverse transcriptipon-PCR was used to detect the expressions of SP-C mRNA and AQP-5 mRNA. Results The sry gene was detected in bleomycin induced lung injury tissues of the rats after MSCs infusion immediately and on the 7th day The MSCs in lung tissue could transformed into cells with ACEⅡ morphological features and molecular phenotype. The transformation rate was higher in the rats received MSCs infusion immediately than the rats received on 7th day. The 5th generation MSCs and fresh bone marrow expressed SP-C mRNA，without AQP-5 mRNA and SP-C expression. Conclusions Exogenous MSCs can be transplanted into injured lung tissues and transform into AECⅡ，especially in early stage of lung injury. The differentiation potential of MSCs can be activated in injury micro-environment.
Objective To evaluate the effects of two different epidermal growth factor receptor tyrosine kinase inhibitors ( EGFR-TKIs) , Gefitinib and Erlotinib, on lung fibrosis induced by bleomycin.Methods Forty BALB/c female mice were randomly divided into four groups, ie. a control group( saline given orally and intratracheally) , a fibrosis group( saline given orally with bleomycin instillation) , a Gefitnib group( Gefitnib 20 mg/kg given orally with bleomycin instillation) , and an Erlotinib group ( Erlotinib25 mg/kg given orally with bleomycin instillation) . Bleomycin ( 3 mg/kg) was intratracheally instilled on the first day. Gefitinib or Erlotinib was given orally daily and normal saline as control. Then they were sacrificed by abdominal aortic bleeding 14 days after the bleomycin instillation. The left lung was stained with HE and Masson’s trichrome staining respectively for pathological examination. Total EGFR and phosphorylated EGFR were detected by immunohistochemistry. Hydroxyproline ( HYP) assay was performed in the right lung.Results Both Gefitinib and Erlotinib significantly reduced lung collagen accumulation and the content of HYP. Immunohistochemistry revealed that phosphorylation of EGFR in lung mesenchymal cells induced by bleomycin was inhibited. Furthermore, there was no difference between Gefitinib and Erlotinib in inhibiting lung fibrosis. Conclusion Our findings suggest that, in the preclinical setting, EGFR-TKIs may have aprotective effect on lung fibrosis induced by bleomycin.
Fibropolycystic liver diseases (FLDs) is a rare genetic disorder, including bile duct hamartomas, congenital hepatic fibrosis, polycystic liver disease, Caroli’s disease, and choledochal cysts. Fibropolycystic liver diseases has received little clinical attention and exhibits a variety of imaging manifestations, leading to a high likelihood of missed diagnosis and misdiagnosis. Through this case, we delineate the characteristic imaging manifestations of the disease and its underlying pathological mechanisms. Our objective is to enhance readers' comprehension of the disease and thereby reduce the rate of missed diagnosis and misdiagnosis of the disease.
Objective To introduce the role of pancreatic stellate cells in pancreatic fibrosis and the progress in treatment of pancreatic fibrosis. MethodsRelevant literatures were collected and reviewed. Results Pancreatic stellate cells activation was closely related to pancreatic fibrosis. Inhibition of pancreatic stellate cells activation could provide a new approach in clinical treatment of chronic pancreatitis. Conclusion Pancreatic stellate cells are the key to pancreatic fibrosis, which are becoming the target for antifibrosis of the pancreas and treatment of chronic pancreatitis.