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Objective:To evaluate the prevention effect of low dose pre-irradiation on irradiation-induced lung injury and its possible mechanism.Methods:Totally 320 6-week-old female C57BL/6j mice were divided into control (0 Gy), low-dose (0.5 Gy), high-dose (20 Gy) and low-dose pre-radiation(0.5 Gy+ 20 Gy)groups by the random number method, with 80 mice in each group. The mice in the low-dose and low-dose pre-irradiation groups were placed in the immobilization device under full consciousness and subjected to 0.5 Gy X-ray whole-body irradiation. 2 weeks later, the 0.5 Gy pre-irradiated mice were anesthetized and subjected to 20 Gy X-rays on chest, as the pre-radiation plus high dose radiation group. The mice in the control group were irradiated with mock irradiation (0 Gy). All mice were terminated at designed time points (24 h, 1 month, 3 months and 5 months) after completion of the irradiation schedule, with 20 mice/group at each time point. Then, lung tissues were taken from mice, and pathological changes were observed by hematoxylin-eosin (HE) staining and Masson′s trichrome staining. RT-qPCR and Western blot were used to detect the expressions of mRNAs and proteins of pulmonary fibrosis-related factors.Results:Pathological changes were observed in the lung tissues 1 month after a single high-dose 20 Gy irradiation, mainly including radiation pneumonitis and a small amount of collagen accumulation, which was more serious than low-dose pre-irradiation group, and these pathological changes became more severe when the time after irradiation increased. Meanwhile, the mRNA and protein levels of proSP-C and HOPX in the low-dose pre-irradiation group were higher than those in the high-dose group, except for proSP-C protein expression at 3 and 5 months post-irradiation. A more significant change was that the mRNA level of TGF-β1 in the high-dose group was 5.8-13.6 times higher than that in the other groups at 5 months after irradiation, as well as β-catenin mRNA ( t=4.22, 5.11, P<0.05). At the same time, in the early period (24 h and 1 month) post-irradiation, the level of vimentin protein in the low-dose pre-irradiation group was significantly higher than that in the high-dose group ( t=6.54, 4.28, P<0.05). Conclusions:When the mice were pre-irradiated with 0.5 Gy X-rays, an adaptive protective response was induced in lung tissues, resulting in the tolerance to subsequent high dose irradiation.
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To investigate the TGFβ1-induced epithelial-mesenchymal transition (EMT) of Huh7 hepatoma cells caused by interaction of hepatitis B spliced protein (HBSP) with transforming growth factor beta-1-induced transcript 1 protein (TGFβ31I1),coding region of HBSP was cloned into lentiviral expression vector.Huh7 hepatoma cells were infected by recombinant lentivirus packaged in 293T cells.Stable cell lines expressing HBSP or control cells were selected by puromycin.Cells were incubated with 5 ng/mL TGFβ1 for 24 h,and observed under contrast-phase microspcope.Then the whole cell lysates were collected for western blot analysis using specific antibodies against EMT markers including E-cadherin,N-cadherin,Claudin-1 and β-catenin.To evaluate the effects of HBSP-TGFβ1I1 interaction on EMT,TGFβ1-induced EMT marker transition,as well as cell invasion and migration were explored after knocking down of TGFβ1I1 by siRNA.Results showed that Huh7 cell lines expressing HBSP (Huh7-HBSP flag-HIV) and control cell lines (Huh7-flag-HIV) were successfully established.Huh7-HBSP flag-HIV cells lost their pebble-like shape and tight cell-cell adhesion and transformed into the mesenchymal-like cells in the presence of TGFβ1.Decreased expression level of epithelial marker of E-cadherin,Claudin-1,β-catenin,increased expression level of mesenchymal marker of N-cadherin,and enhanced migration and invasion abilities were observed in Huh7-HBSP-flag-HIV cells as compared to the control cells.Moreover,the changes of EMT markers and metastasis abilities of Huh7-HBSP-flag-HIV cells could be reversed when TGFβ111 was knocked down by siRNA.In conclusion,HBSP could promote hepatoma cell migration and invasion by triggering EMT via interaction with TGFβ111.Our findings highlight new insights for HBSP-induced HCC progression.
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Objective To observe hepatitis B virus (HBV) reactivation in 12 patients with rheumatic disease undergoing immunosuppressive therapy and to evaluate whether preemptive antiviral therapy is necessary for patients receiving disease-modifying anti-rheumatic drugs (DMARDs).Methods From January 2008 to March 2012,a total of 12 HBV-infected patients with rheumatic diseases were consecutively enrolled into this long-term follow-up study.Liver function and serum levels of HBV DNA were tested during the follow-up.Results The medium duration of follow-up was 41 months (range 16-48).Four patients received steroid treatment,and among them two patients without pre-emptive antiviral therapy developed HBV reactivation.After administr-ation of LAM or ETV,HBV replication was controlled in both patients.Five patients were treated with disease-modifying anti-rheumatic drugs and the other three patients received tumor necrosis factor-alpha-blocking agents.None of these patients received pre-emptive antiviral therapy.HBV reactivation did not occur in any of them.Conclusion HBV reactivation does occur in HBV-infected patients with rheumatoid diseases after immunosuppressive therapy.Pre-emptive antiviral therapy should be administered in patients who are receiving steroid therapy for rheumatic diseases.In contrast,DMARDs and TNFBA are relatively safe for HBV-infected patients with rheumatic diseases.Close monitoring of HBV DNA and ALT levels is necessary to the mana-gement of HBV reactivation.
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Objective The aim of the study was to observe the features of nail fold microcirculation in systemic sclerosis (SSc) patients and to compare these findings in SSc patients with patients with other connective tissue diseases.Methods Forty patients with SSc and thirty-seven patients with other connective tissue diseases were included in the study and all the patients reported symptoms of Raynaud's phenomenon in the hands were also included.Nail fold capillaroscopy (NFC) was performed and the abnormality of nail fold microcirculation between the two groups were compared.The relations between nail fold capillaroscopic findings and clinicolaboratory parameters in SSc patients were analyzed.Statistical analysis were carried out by t-test and Chi-square.Results The loss of capillaries and dilated and giant capillaries and hemorrhage as well as neoangiogenesis were hallmarks of the scleroderma capillary findings,which could be detected by nail fold capillaroscopy.The abnormalities of nail fold microcirculation in SSc patients were more severe and more specific than those in other connective tissue disease patients.The total scores of nail fold capillaroscopy test were obviously higher in SSc patients with lung or esophagus involvement than those patients without these organ involvement,meanwhile,the total scores of nail fold capillaroscopic findiugs were elevated in SSc patients with anti-Scl70 antibody than those with negative group.Conclusion The nail fold capillaries of patients with SSc have specific abnormalities,and nail fold capill-aroscopy could distinguish between SSc and other connective tissue diseases,therefore it could be used as a promising tool for early detection of patients who may have the potential to develop scleroderma and it is also helpful in assessing disease severity.
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Literatures on arrhythmia induced by acute organophosphorous pesticide poisoning published in domestic journals from 1979 to 2010 were searched. Total 3468 cases of acute organophosphorous poisoning were collected and analyzed. The average abnormal ECC rate was (53 ±15)%(35. 4% -68. 4% ) in acute organophosphorous poisoning, the most common ECG abnormalities were ST-T segment changes (26. 5% ) and sinus tachycardia (16. 6% ). The rate and severity of ECG abnormalities were increased with the severity of organophosphorous poisoning(x2 = 33. 253,P < 0. 01). The most common causes of death in acute organophosphorous poisoning were ventricular tachycardia and ventricular fibrillation (26.2%).
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Objective To investigate the effects of dexamethasone(DEX)on the secretion of interleukin (IL)-17 and interferon(IFN)-γ and the proportion of Th17,Tc17,Th1 ,Tc1 cells in peripheral blood mononuclear cells(PBMCs)of patients with systemic lupus erythematosus(SLE). Methods Thirty hospitalized SLE patients were recruited and twenty-two healthy volunteers were recruited as healthy controls. PBMCs were separated from SLE patients and healthy controls and then was cultured in vitro by medium or PMA/Ionomycin or PMA/Ionomycin +dexamethasone for six hours. Four- color immunofluorescent staining and flow cytometric assay were used to analyze the percentage of Th17,Tc17,Th1,Tc1 cells in PBMCs. Concentrations of IL-17 and IFN-γ in plasma and the supernatants of PBMCs which were cultured for 24 hours were measured by enzyme linked immunosorbent assay (ELISA). Results The plasma concentrations of IL-17 and IFN-γwere elevated in SLE patients as compared to the controls(P ＜ 0.05). No significant differences were observed between patients and controls for the spontaneous production of IL-17 and IFN-γ or percentage of T subsets expressed by PBMCs. After the stimulation of PMA,compared with the controls,the level of IL-17 was significantly elevated in the supematants of PBMCs and the percentages of Th17 and Tc1 in SLE patients increased significantly(P ＜ 0. 05). However,there showed no significant differences between SLE patients and the controls for the percentages of Th1 and Tc17 cells. DEX could significantly decrease the production of IL-17(P ＜ 0. 01)and the percentages of Th17,Tc1 cells by the active PBMCs(P ＜ 0. 05). Conclusions There is abnormal expression of T subset cells and their cytokines in vivo of SLE patients. DEX can interfere with immunological pathological process in the cytokine network imbalance of SLE patients and shows powerful inhibition of IL - 17. Our results may provide some laboratory evidence for the clinical application of corticosteroids.
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Objective To investigate infectious complications and analyze their risk factors in patients with systemic lupus erythematosus (SLE) and provide clue for antibiotics treatment. Methods Patients with SLE admitted to our hospital between 2002 and 2007 were. reviewed, and the characteristics of their infections including the infection sites, pathogens and the drug resistance of pathogenic bacteria were investigated. The suspected risk factors of infections in patients with SLE were selectod and then analyzed by chi-square test and Logistic regression. Results The prevalence of infection in this group of patients was 24.4% (130/533). One patient died from respiratory tract infection. The common infection sites were respiratory tract (56.9%), urinary tract (23.8%) and skin (18.5%). Bacteria were the most common pathogens of infections in SLId pa-tients (53.3%), the majority of which were gram-negative bacteria. The second major pathogen was fungus (39.2%), and the third was the combination of bacteria and fungus. There were 7 patients with tuberculosis. The common strains causing infections in SLE patients were. Escheriehia coli, Klebsiella pneumonea, Pseu-domonas aeruginosa, Staphylococcus aureus and Candida albican. Antimicrobial susceptibility tests showod that the drug resistant rates increased rapidly. The gram-negative ones were sensitive to eefoperazone-sulbac-tam and carbopenems. The infection-related risk analysis suggested that the independent risk factors of infections in SLE patients included old age, hypopruteinemia, moderate anemia and high dose of eorticos-teruids treat-ment. Conclusion Those patients with infection-related risk factors should be monitored closely for infec-tions. Respiratory tract and urinary tract are the most common infectious sites in SLId patients, and gram-nega-tive bacteria are the major pathogens, so antibiotics such aa cefoperazone-sulbactam or carbopenems may be good choices before the result of antimicrobial susceptibility test information is available.