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Objective:To evaluate the effects of different doses of sivelestat sodium on perioperative acute lung injury (ALI) in the patients undergoing emergency surgery for acute Stanford type A aortic dissection (AAAD).Methods:A total of 120 patients of both sexes, aged 30-64 yr, with body mass index of 18.5-24.9 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅲ or Ⅳ, scheduled for emergency AAAD surgery, were divided into 3 groups using a random number table method: low-dose sivelestat sodium group (SL group), medium-dose sivelestat sodium group (SM group)and high-dose sivelestat sodium group (SH group), with 40 patients in each group. Sivelestat sodium 4.8, 6.0 and 7.2 mg/kg were intravenously infused starting from 10 min before anesthesia until 24 h after surgery in SL, SM and SH groups, respectively. Blood samples from the radial artery were collected for blood gas analysis after anesthesia induction and before skin incision (T 1), immediately after the end of surgery (T 2), at 24 h after surgery (T 3), and 72 h after surgery (T 4), the alveolar-arterial oxygen tension difference (PA-aDO 2), oxygenation index (OI)and respiratory index (RI) were calculated. The duration of postoperative mechanical ventilation, length of stay in the intensive care unit (ICU) and length of postoperative hospital stay were recorded. Central venous blood samples were collected at T 1-T 4 to measure serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6)and IL-8. Peripheral venous blood samples were collected on preoperative day 1 and postoperative days 1 and 3 to measure white blood cell (WBC) count, neutrophil (NEUT) count, neutrophil percentage (NEUT%), and C-reactive protein (CRP) concentration. The occurrence of postoperative pulmonary complications (PPCs)and 90-day all-cause mortality were recorded. Results:Compared with the baseline at T 1, PA-aDO 2 and RI were significantly increased, OI was decreased, and the serum concentrations of TNF-α, IL-6 and IL-8 were increased at T 2-T 4 in all the three groups ( P<0.05). WBC, NEUT, NEUT% and concentrations of CRP were significantly higher on postoperative days 1 and 3 than on 1 day before surgery in the three groups ( P<0.05). Compared with SL and SM groups, PA-aDO 2 and RI were significantly decreased, OI was increased, and the serum concentrations of TNF-α, IL-6 and IL-8 were decreased, the WBC count, NEUT count, NEUT% and concentrations of CRP were decreased, the incidence of postoperative hypercapnia, hypoxemia, emerging lung rales and bronchospasm was decreased, and the duration of postoperative mechanical ventilation and length of intensive care unit stay were shortened( P<0.05), and no significant change was found in the postoperative length of hospital stay and 90-day all-cause mortality rate in SH group ( P>0.05). Conclusions:Sivelestat sodium 7.2 mg/kg can significantly inhibit the inflammatory responses, alleviate perioperative ALI, and improve early prognosis in the patients undergoing AAAD surgery.
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Objective To investigate the effects of sivelestat sodium on early inflammatory reaction in rats with smoke inhalation injury. Methods Forty SPF male SD rats were randomly divided into 5 groups:normal control group (A), injury group (B), smoke inhalation treated with 10 mg/kg sivelestat sodium group (C), smoke inhalation treated with 20 mg/kg sivelestat sodium group (D) and smoke inhalation treated with 30 mg/kg sivelestat sodium group (E), 8 rats for each group. After smoke inhalation injury model was established, the treatment groups were intraperitoneally injected sivelestat sodium 10 mg/kg, 20 mg/kg and 30 mg/kg separately. B group was treated with the same volume of physiological saline. After 24 hours,ELISA was used for detecting serum contents of neutrophil elastase (NE), myeloperoxidase (MPO), tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) in five groups. Meanwhile the water content of lung tissue was measured, and the pathological changes were observed by HE staining. The thickness of alveolar septum was measured and compared between groups. Results Compared with control group, the serum levels of NE, MPO, IL-6, TNF-α, water content of the lung tissue and thickness of alveolar septum were significantly higher in other four groups (P<0.05). Compared with injury group, the serum levels of NE, MPO, IL-6, TNF-α, water content of the lung tissue and thickness of alveolar septum were significantly lower in treatment groups (P<0.05). Compared with 20 mg/kg treatment group and 30 mg/kg treatment group, the serum levels of NE, MPO, IL-6, TNF-α, water content of the lung tissue and thickness of alveolar septum were significantly lower in 10 mg/kg treatment group (P<0.05). Conclusion The result shows that sivelestat sodium can reduce the early inflammatory reaction of rats with smoke inhalation injury and attenuates the lung edema. In this experiment, the treatment effect of 10 mg/kg sivelestat sodium is better than other treatment doses.
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Objective To assay the level of neutrophil extracellular traps (NETs) in systemic lupus erythematosus (SLE) patients and healthy controls and compare the difference between SLE group and control group, and to analyze between the level of NETs and related laboratory parameters. Methods Forty-four females patients with SLE were recruited as research subjects, with 24 cases in the active stage and 20 in stable stage. Forty-two healthy female volunteers matched in age were enrolled as control subjects. The fluorescence intensity of NETs in neutrophils was detected by fluorospectrophotometry. The concentration of neutrophil elastase in plasma was quantitatively detected. Statistical analysis of the difference of level of NETs between the SLE group and control group was conducted. Then the correlation between the fluorescence intensity of NETs and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and anti-double-stranded DNA (dsDNA), and anti-histone, and anti-nucleosome, and systemic lupus erythematosus disease activity index (SLEDAI) was analyzed respectively. The same tests were conducted for the level of NE. The results of the two groups were compared using analysis of variance and the relevance was analyzed using Spearman correlation analysis. NETs morphosis was observated by immunoflurescence method, and the difference of NETs between SLE group and control group was analyzed. Results ① The fluorescence intensity of NETs was significantly increased in SLE group(241±139) than that in the control group (173±135), (t=2.31, P0.05] and NE concentration [(104±43) vs (96±48), t=0.50, P>0.05] between SLE active stage and stable stage was detected. ③ The fluorescence intensity of NETs in SLE patients was positively correlated with SLEDAI, but had no obvious correlation with anti-dsDNA, anti-histone, anti-nucleosome, CRP or ESR, respectively. ④Images under confocal microscope showed that more NETs generated by PMN from SLE patients than that from controls. Conclusion The generation of NETs is enhanced in female patients with SLE. And NETs may relate to disease activity. However, NETs may not induce the production of autoantibodies.
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The transcription factor p73 belongs to the p53 family of tumor suppressors,and can be transcribed into different isoforms with either pro-or anti-apoptotic(TAp73 and △Np73)functions.However,the tumor suppressor activity of TAp73 is inhibited through complex formation with inhibitory proteins(e.g.△Np73,mutant p53,MDM2 and iASPP).Therefore,it is a kind of tumor therapy strategy to reactivate TAp73 through targeting these inhibitors directly or release TAp73 from the complex by targeting their interaction.This review discusses the possible strategies of targeting p73 for its reactivation and the acting mechanism of related compounds.
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Objective To investegate the effect of ginsenoside Rg1 on the apoptosis related protein FLICE-inhibitory protein(FLIP),Fas-associated death domain protein (FADD)and Caspase-3 in the subatania nigra(SN)of 1-methyl-4-phenyl-1,2,3,6-tetrahyd-ropyridine (MPTP)-induced mouse models of Parkinson’s disease(PD), and to investigate the role of FADD and FLIP in the pathogenesis of PD and the protective effect of ginsenosides Rg1 on dopaminergic neurons.Methods 45 C57BL/6N mice were randomly divided into control group,model group and ginsenoside Rg1 group (n=15).The mice in model group were injected with MPTP by intraperitoneal,the mice in Rg1 group were injected with ginsenoside Rg1 before injecting MPTP,and the mice in control group were injected with normal saline by intraperitoneal. The behavioral changes of the mice in various groups were observed, and immunohistochemistry and Western blotting methods were used to observe the expressions of tyrosine hydroxylase (TH),FADD,FLIP and Caspase-3 in substantia nigra of the mice.Results Compared with control group,the mice in model group presented with typical symptoms of PD, the TH-positive neurons in the subatania nigra was significantly reduced (P<0.01 ), the number of FADD, FLIP and Caspase-3 positive cells was significantly increased(P<0.01),and the cytoplasm was deeply stained;the protein expression levels of FADD,FLIP and Caspase-3 were significantly increased (P<0.01).Compared with model group,the PD symptoms of the mice in ginsenoside Rg1 group reduced, the number of TH-positive neurons was significantly increased, the number of positive cells of FLIP,FADD and Caspase-3 were significantly reduced(P<0.01),and the cytoplasm was lightly stained;the protein expression levels of FADD, FLIP and Caspase-3 were significantly reduced (P<0.01 ). Nonlinear correlation analysis found that there was a positive relationship between the number of FADD and Caspase-3 positive cells (r=0.791,P<0.05).Conclusion Ginsenoside Rg1 may play a neural protective effect dopaminergic on neurons by modulating the FADD and FLIP expressions in SN of PD model mice.
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Objective To investigate the effect of neutrophil elastase (NE) inhibitor on the blood-brain barrier(BBB) permeabili-ty and hydrocephalus in rats with traumatic brain injury (TBI) .Methods 99 SD rats were randomly divided into the control group , the TBI group and the intervention group(dividing into 5 sub-groups:6 ,24 ,48 ,72 ,168 h) .The hydraulic impact model of rats was duplicated .Sivelestat sodium was given in the intervention group .The NE concentration in the brain tissue ,BBB permeability and brain water content were detected in each group and performed the comparative analysis .Results The NE concentration in the brain tissue ,BBB permeability and brain water content at each timepoint in the TBI group and the intervention groups were higher than those in the control group .The NE concentration at 24 ,48 ,72 ,168 h in the intervention group was lower than that in the TBI group .The BBB permeability and the brain water content at 48 ,72 ,168 h in the intervention group were lower than those in the TBI group(P<0 .05) .Conclusion Sivelestat sodium can inhibit the NE release in TBI rat brain tissue ,reduce the BBB permeability and the occurrence of hydrocephalus ,which indicating that sivelestat sodium has the protective effect on TBI secondary lesion in rat .
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Objective To investigate the efficiency of biology function of ITIH4 gene silenced by small interfering RNA (siRNA) on ovarian cancer.Methods The four pairs ITIH4 gene siRNA interference fragments(ITIH4-546,ITIH4-795,ITIH4-917 and ITIH4-1568) were designed respectively,and transfected into HO8910pm cells with ITIH4 mRNA high expression by liposomal method transiently.Quantitative PCR method was used to detect the ITIH4 mRNA expression in HO8910pm cells transfected with interference fragment.The ITIH4 917 was selected as the best silencing effect of siRNA interference fragment and then the recombinant plasmid expression vector pGPU6/GFP/Neo-shRNA-ITIH4-917 was constructed and transfected into HO8910pm cells.The stably transfected cells-pGPU6/GFP/Neo-shRNA-ITIH4-917-HO8910pm cells was obtained by screening of aminoglycoside antibiotics (G418).The experiment was divided into three groups,namely ITIH4-917 transfection group,the HO8910pm cell group transfected with pGPU6/GFP/Neo-shRNA plasmid (empty vector group),and the HO8910pm cell group transfected with pGPU6/GFP/Neo-shRNA-ITIH4-NC the plasmid (negative control group).Fluorescence quantitative reverse transcription(RT)PCR and western blot were used to detect the ITIH4 mRNA and protein expression.The cell proliferation,the cell cycle,colony formation of cells,cells migration and invasion in vitro were determined by using methyl thiazolyl tetrazolium (MTT),flow cytometry,colony formation assay and transmembrane (transwell) small chamber method [value represented by absorbance (A)],respectively.Results The fluorescent quantitative PCR results showed that the ITIH4 mRNA expression levels in ITIH4-917 HO8910pm cells was significantly lower than that in the control cells,the relative copy number was only 0.26 ± 0.15.Also the relative copy number of ITIH4 mRNA in ITIH4-917 transfection group cells was 0.34 ±0.10,it significantly lower than that in empty vector group (1.87 ±0.12,P =0.008) and negative control group (1.58 ±0.21,P =0.032) ; Western blot results showed that the ITIH4 relative expression levels of the protein in ITIH4-917 HO8910pm group cells,empty vector group and negative control group were 0.51,1.64 and 1.74,respectively,there were statistically significant differences (0.51 vs.1.64,P =0.012; 0.51 vs.1.74,P =0.014).MTT colorimetric assay showed that the proliferation of ITIH4-917 HO8910pm group cells was significantly faster than that in the empty vector group and negative control group,and there were statistically significant differences among them (P =0.001).The S ± G2/M phase cell ratio in ITIH4-917 HO8910pm group cells was 54.2％,which was significantly higher than that in the empty vector group or negative control group (26.3％ and 31.3％,respectively,all P ＜ 0.05).The colony formation rate (55.7 ± O.7) ％ in ITIH4-917 HO8910pm group cells was also significantly higher than that in empty vector group (29.7 ±0.9) ％ (P =0.037) and negative control group (31.4 ± 0.3) ％ (P =0.043).Migration and invasion experiments showed that cell migration in ITIH4-917 HO8910pm group cells was 0.40 ± 0.18,whicht was significantly higher than that in the negative control group or empty vector (0.30 ±0.03,P =0.031 ;0.25 ±0.03,P =0.028,respectively).Although the invasive ability of ITIH4-917 HO8910pm group cells (1.31 ±0.34) was higher than that in the control cells (1.05 ±0.68) and empty vector group (1.14 ±0.08),while there were not significant difference (P ＞ 0.05).Conclusion It would be to promote the cell doubling time and increase the migration capability in HO8910pm cells that ITIH4 expression was down-regulating by ITIH4 mRNA interference.