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.
ObjectiveTo investigate the effect of diammonium glycyrrhizinate (DG) plus bone marrow mesenchymal stem cells (MSCs) transplantation in the treatment of acute exacerbation of pulmonary fibrosis induced by bleomycin (BLM) in rats.MethodsMSCs were isolated from male Wistar rats and cultured in vitro. Twenty-four female Wistar rats were randomly divided into 4 groups. The NC group was intratracheally injected with normal saline; the BLM group, the MSC group and the DGMSC group were intratracheally injected with BLM for 7 days; then the MSC group was injected with 0.5 mL of MSCs solution (2.5×106 cells) into the tail vein; the DGMSC group was intraperitoneally injected with DG for 21 days in a dose of 150 mg·kg–1·d–1 on the base of the MSCs injection. The rats were sacrificed on the 28th day and the lung tissue was extracted. Pathological examination was performed to determine the degree of alveolitis and pulmonary fibrosis. Immunofluorescence was used to detect the number and distribution of alveolar type Ⅱ epithelial cells. Alkali hydrolysis method was used to determine the content of hydroxyproline (HYP) in lung tissue; thiobarbituric acid method was used to measure the content of malondialdehyde (MDA) in lung tissue; colorimetric method was used to determine the superoxide dismutase activity (SOD) and total antioxidant capacity (T-AOC); enzyme linked immunosorbent assay was used to detect the expression levels of tumor necrosis factor-α (TNF-α ) and transforming growth factor-β1 (TGF-β1) in lung tissue homogenates.ResultsThe DG combined with MSCs injection can reduce the degree of alveolitis and pulmonary fibrosis in BLM model rats. The content of HYP and TGF-β1 in lung tissue homogenate of the DGMSC group were significantly lower than those in the MSC group (P<0.05). Meanwhile, DG combined with MSCs injection significantly increased the antioxidant capacity of the BLM model rats. MDA content decreased, SOD activity and T-AOC ability improved significantly in the DGMSC group compared with the MSC group (P<0.05). The alveolar type Ⅱ epithelial cells were significantly increased and the cell morphology was maintained in the DGMSC group compared with the MSC group.ConclusionsDG has a synergistic effect with MSCs in treatment of acute exacerbation of pulmonary fibrosis. The mechanism may be related to reducing inflammatory factors during pulmonary fibrosis, attenuating oxidative stress and promoting MSCs migration into lung tissue and transformation to alveolar type Ⅱ epithelial cells.
Objective To study the prevalence of combined pulmonary fibrosis and emphysema (CPFE) in a community-based lung cancer screening program in Shanghai. Methods From June 2018 to July 2019, eligible participants who were assessed through a high-risk lung cancer questionnaire in Xuhui, Shanghai underwent low-dose computed tomography of the lungs. The suspected CPFE patients were invited to provide medical history and blood for analysis, and received high-resolution CT (HRCT) scanning for confirmation. Results Of the 15 cases of suspected CPFE from a total of 4478 participants in which 1704 males and 2774 females, 4 declined further examination and 11 received further examine. Eight subjects were confirmed as CPFE, and all were male, of whom two were ex-smokers and six were active smokers. These CPFE patients had cough, chest tightness and dyspnea. There were 3 cases of centrilobular emphysema, 2 cases of paraseptal emphysema, 1 case of panlobular emphysema and 2 cases of mixed emphysema. There were 2 cases of usual interstitial pneumonia, 3 cases of non-specific interstitial pneumonia, 2 cases of airspace enlargement with fibrosis and 1 case of unclassifiable smoking-related interstitial fibrosis. The KBILD scores were 61.7±7.5 and mMRC scores were 1.5±0.8. Serum Krebs von den Lungen-6 concentration was (380.75±212.05)U/mL. Lung function test showed normal or mild restrictive ventilatory function, and mild-moderate impairment in diffusion capacity. Conclusions The prevalence of CPFE is 1.79‰ in a community-based lung cancer screening population, and is 4.69‰ in male lung cancer screening population.
Objective To investigate the role of IFN-γ in suppressing bleomycin-induced pulmonary fibrosis in rats.Methods Seventy-five SD rats were randomly divided into five groups (15 rats in each group)，ie.a normal group，a bleomycin-induced pulmonary fibrosis model group，a dexamethasone-treated group，a high-dose IFN-γ-treated group (150 000 U/kg) and a low-dose IFN-γ-treated group (50 000 U/kg).Five rats in each group were randomly killed in 7th day，14th day and 28th day after relative treatment respectively，and lung tissue samples were harvested for histopathology study.HE and Masson staining were used to determine the extent of alveolus inflammation and pulmonary fibrosis respectively.Histoimmunochemical method were adapted to determine protein levels of TGF-β1，CTGF，type Ⅰcollagen and type Ⅲ collagen in pulmonary tissues.Results Histopathological study showed that treatment with either dexamethasone or IFN-γ (both high dose and low dose) remarkably meliorated the extent of alveolus inflammation and suppressed pulmonary fibrosis (compared with model group，all Plt;0.05).Histoimmunochemical study suggested that both dexamethasone and IFN-γ could inhibit the expression of TGF-β1，CTGF，type Ⅰand type Ⅲ collagen (compared with model group，all Plt;0.05)，and the suppression of TGF-β1，type Ⅰand type Ⅲ collagen expression was more obvious in high-dose IFN-γ-treated group than those in low-dose group (Plt;0.05).Conclusions INF-γ possesses apparent anti-fibrosis effect that is similar to dexamethasone but with less side effect.Such effect may resulted from reduced production of type Ⅰand type Ⅲ collagen through expression inhibition of cytokines such as TGF-β1 and CTGF.
ObjectiveTo investigate the molecular pathogenesis of pulmonary fibrosis induced by bleomycin in a murine model,and provide novel insights for clinical diagnosis and treatment.
MethodsFrom Gene Expression Omnibus,we downloaded microarray data extracted from experiments of bleomycin induced pulmonary fibrosis in wild-type mice. With BRB-Array Tools,differentially expressed genes at different time points during disease development were screened,selected and analyzed by DAVID software.
ResultsBRB array analysis identified 45101 differentially expressed genes. After induction by bleomycin on 7th day,1164 genes and 735 genes were significantly up-regulated and down-regulated (P<0.05,fold change>2),respectively. On 14th day,731 genes and 390 genes were significantly up-regulated and down-regulated (P<0.05,fold change>2),respectively. DAVID analysis revealed that the up-regulated genes were significantly enriched in cell cycle,p53 signaling and chemokine signaling pathway,damaging reaction and collagen metabolism gene sets. While the down-regulated genes were enriched in the drug metabolism pathway gene set.
ConclusionsBioinformatics methodologies are able to efficiently analyze microarray data and extract its underlying information,provide novel insights for major molecular events and shift of cell signaling pathway during pulmonary fibrosis progression,and furthermore,finding molecular markers for early diagnosis and therapeutic targets.
Objective To investigate the prevalence of obstructive sleep apnea hypopnea syndrome ( OSAHS) in patients with idiopathic pulmonary fibrosis ( IPF) and its clinical significance. Methods Sleep quality and breathing disorders were measured by polysomnography and the relationship with lung function was analyzed in 20 IPF patients. Results Thirteen of 20 subjects ( 65% ) had OSAHS as defined by an AHI ≥5 events per hour. Three subjects ( 15% ) had mild OSAHS ( AHI,5 to 20 events per hour) , and 10 subjects ( 50% ) had moderate-to-severe OSAHS ( AHI≥20 events per hour) . The sleep architecture in these patients showed a reduction in sleep efficiency, rapid eye movement ( REM) sleep and slow wave sleep, and a marked sleep fragmentation due to an increased arousal index. The AHI was negatively correlated with FVC% pred ( r =-0.672, P=0.001) and FEV1% pred ( r =-0.659, P=0.002) , and positively correlated with body mass index ( BMI) ( r=0.791, Plt;0.0001) . Conclusions OSAHS is a common comorbidity in IPF. Early treatment of OSAHS may improve quality of life and the prognosis of patients with IPF.
Abstract:Objective To observe the expression of calcium-dependent proline-rich tyrosine kinase-2（Pyk2） in myocardium of rheumatic heart disease, the relationship between its role and cardiac fibrosis and clinical significance. Methods The blue myocardium collagen stain were analysed after Masson staining in 30 patients with rheumatic heart disease （RHD group） and 6 normal myocardium specimens （control group）. The contents of hyaluronic acid （HA）, laminin（LN） and type IV collagen（IV-C） were detected by radio-immunity method,and the expressions of Pyk2 protein and messenger ribonucleic acid（mRNA） were explored by immunohistochemistry methods and reverse transcriptase polymerase chain reaction （RT PCR）,then the correlations of these results were statistically analyzed. Results The contents of HA,LN and IV C in RHDgroup increased compared to control group（174.95±76.14μg/L vs. 70.06±15.63μg/L, 153. 86 ± 20. 72μg/L vs. 90.01±14. 11μg/L, 95. 26±7.66μg/L vs. 63. 21±10.62μg/L; P= 0.003, 0. 013, 0. 035）. The Pyk2 absorption and the ratio of Pyk2 mRNA/glyceraldehyde phosphate dehydrogenase （GAPDH） in RHD group were significantly higher than those in control group （0. 325 ± 0. 032 vs. 0.106±0.013, 0.870±0.085 vs. 0.573±0.042; P=0.048, 0.006）.There were positive correlativity between the expression of Pyk2 protein and HA, LN and IV-C （r=0. 611, 0. 743, 0. 829, P〈0. 01）, there were positive correlativity between the expression of Pyk2 mRNA and LN, IV-C （r=0. 794, 0. 766, P〈0.05）. Conclusion Pyk2 may play a key role in the proceeding of cardiac fibrosis in rheumatic heart disease by increasing collagen synthesis in myocardium.
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 observe the survival, migration, and effect of human amniotic epithelial cells (hAECs) on hepatic fibrosis in immune rats so as to provide the experimental theory for the clinical treatment with hAECs.
MethodsSixty-four 10-week-old male Sprague Dawley rats (weighing, 220-280 g) were randomly divided into 4 groups, sixteen rats in each group. Rat hepatic fibrosis model was induced in groups A, B, and C; hepatic fibrosis rats were injected with 4×106 hAECs in group A, and with normal saline in group B, and no treatment was given in group C; group D served as control group. After 2 weeks of transplantation, the expression of human Alu gene repeat sequence was detected by DNA-PCR method and human leucocyte antigen G (HLA-G) by immunohistochemical staining in heart, liver, spleen, kidney, lung, and brain in group A, and then the percentage of positive expression was compared between organs except spleen. Semi-quantitative analysis was done for liver fibrosis with HE staining according to Chevallier semi-quantitative histological liver fibrosis scoring system, and immunohistochemical staining for TGF-β1 was used to record immunohistochemical score (ISH), the concentrations of aspartate transaminase (AST), alanine aminotransferase (ALT), and albumin (ALB) were determined to analyze hepatic fibrosis.
ResultsAlu gene repeat sequence and HLA-G could be detected in liver, heart, brain, lung, and kidney in group A, the percentage of positive expression in the liver was significantly higher than that in the other organs (P<0.05). The histological semi-quantitative score of group A (10.47±3.20) was significantly lower than that of groups B and C[(13.84±3.46) and (13.85±3.16)](P<0.05), but no significant difference was found between groups B and C (P>0.05). The ISH scores in groups A, B, C, and D were 3.60±1.50, 5.38±2.60, 5.50±2.40, and 1.87±1.36, respectively; groups A, B, and C were significantly higher than group D, and group A was significantly lower than groups B and C (P<0.05), but there was no significant difference between groups B and C (P>0.05). The concentrations of ALT and AST in groups A, B, and C were significantly higher than those in group D, and group A was significantly lower than groups B and C (P<0.05), but there was no significant difference between groups B and C (P>0.05). The concentration of ALB in groups A, B, and C was significantly lower than that in group D, and group A was significantly higher than groups B and C (P<0.05), but there was no significant difference between groups B and C (P>0.05).
ConclusionhAECs can survive in immune rats by intrasplenic transplantation and migrate to liver, heart, brain, lung, and kidney, and the liver shows the largest migration. The transplantation of hAECs in immune rat with cirrhosis can alleviate hepatic fibrosis and improve the serum indexes of liver function.
ObjectiveTo investigate the effect of echinococcus granulosus protoscolices on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into fibroblasts.MethodsFemur bone marrow of 4-week-old C57BL/6 mice was taken and BMSCs were isolated and cultured by adherent culture. Echinococcus granulosus protoscolices was extracted from the liver of sheep infected with echinococcus granulosus. The experiment was divided into two groups. The experimental group was co-cultured with the 3rd generation BMSCs and the echinococcus granulosus protoscolices, and the control group was the 3rd generation BMSCs. Before and after co-culture, the morphology of BMSCs and the activity of echinococcus granulosus protoscolices were observed by inverted microscope. After cultured for 1, 3, 5, and 7 days, the mRNA expressions of transforming growth factor β1 (TGF-β1), collagen type Ⅰ, and collagen type Ⅲ were detected by real-time fluorescent quantitative PCR, the protein expressions of TGF-β1, collagen type Ⅰ, collagen type Ⅲ, Smad7, and phosphorylated Smad2/3 were detected by Western blot, and the contents of collagen type Ⅰ and collagen type Ⅲ in the supernatant of the two groups were detected by ELISA.ResultsAfter 7 days of co-culture, the morphology of BMSCs changed into fusiform and irregular triangle, which was closer to the mouse fibroblasts. The relative mRNA expressions of TGF-β1, collagen type Ⅰ, and collagen type Ⅲ in the experimental group were significantly higher than those in the control group; the relative protein expressions of TGF-β1, collagen type Ⅰ, collagen type Ⅲ, and phosphorylated Smad2/3 in the experimental group were significantly higher than those in the control group, and the relative protein expression of Smad7 in the experimental group was significantly lower than that in the control group; the contents of collagen type Ⅰ and collagen type Ⅲ in the supernatant of the experimental group were significantly higher than those in the control group. The differences between the two groups were significant (P<0.05).ConclusionEchinococcus granulosus protoscolices may promote the secretion of collagen type Ⅰ, collagen type Ⅲ, and TGF-β1 by TGF-β1/Smad signal pathway, which can promote the fibrosis of BMSCs that related to the formation of fibrocystic wall by echinococcosis.
