Nuclear factor-erythroid 2 related factor 2 (Nrf2) is an ubiquitous and important transcription factor. It regulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. A large body of research showed that Nrf2-Keap1 (Kelch-like ECH-associated protein 1, Keap 1)-ARE signaling pathway is involved in the endogenous antioxidant defense mechanisms. Nrf2 increases the expression of a number of cytoprotective genes, protects cells and tissues from the injury of a variety of toxicants and carcinogens. As a result, Nrf2 enhances the expression of glutathione and antioxidants such as superoxide dismutase and glutathione S-transferase, and subsequently scavenging free radicals. Air pollution especially from PM2.5 particles, is associated with an increasing morbidity of inflammatory pulmonary diseases and their deterioration. More and more studies demonstrated that Nrf2 was a novel signaling molecule in the modulation of inflammatory responses in these inflammatory respiratory diseases, such as asthma, acute lung injury (ALI) and COPD. Therefore, Nrf2 targeting might be a therapeutic target, which will provide clinical benefit by reducing both oxidative stress and inflammation in asthma, acute lung injury (ALI) and COPD. This review focused on the relationship between Nrf2 and inflammatory respiratory diseases and oxidative stress.

Objective To explore the recovery rate of exhale CO 2 and energy expenditure in the patients with cirrhosis.Methods The recovery rate of exhale CO 2 and energy expenditure in fourteen patients with cirrhosis and eleven healthy subjects were measured by using NaH 13 CO 3 as tracer.After overnight fast,all subjects were intravenously given NaH 13 CO 3 at a primed constant rate of infusion for two hours after a saturating dose infusion.Amount of 13 CO 2 in exhale air was measured using stable isotope mass spectrometry analysis,and the recovery rate of exhale CO 2 and energy expenditure were calculated.Results The recovery rate of exhale CO 2 in patients with Cirrhosis was (80 7?0 26)%,and in healthy control subjects was (78 3?0 84)%,which showed a significantly different between the two groups(P0 05)[(30 2?2 4)Kcal?kg -1 ?d -1 and (28 4?3 5)Kcal?kg -1 ?d -1 ,respectively].Conclusions The results provide theoretical basic to calculate meals for nutritional therapy in the patients with cirrhosis.

Objective To investigate the effects of the leflunomide active metabolite (A771726) on the expression of phorbol-12-myristate-13-acetate (PMA) -induced CD147, matrix metallo-proteinase (MMP)-2 and MMP-9 on THP-1 cells. Methods THP-1 cells were cultured in RPMI-1640 medium supplemented with 10％ fetal bovine serum. For all experiments, THP-1 cells were cultured at an initial density of 5×105/ml. Before A771726 treatment, cells were cultured with serum-free RPMI-1640 medium for 12 h, THP-1cells were co-cultured with PMA at three different concentrations of A771726 (5, 15 , 45 μg/ml) for 24 h.The mRNA expression of CD147, MMP-2 and MMP-9 was measured by real-time PCR. CD147 expression on the cells were evaluated by flow cytometric analysis. The activity of MMP-2 and MMP-9 were evaluated by gelatin zymography. Statistical differences among the groups were tested by one-way ANOVA or KruskalWallis test. Results The expression of CD147, MMP-2 and MMP-9 were upgraded by the PMA. The expression of CD147 on THP-1 cells was inhibited significantly by A771726 in a dose-dependent pattern (P＜0.01). The mean fluorescence intensity (MFI) of CD147 in positive control group was 109.5±3.8, the MFI in A771726 (5, 15, 45 μg/ml) group were 73.3±2.5, 64.5±2.3, 40.9±2.7, respectively. The expression of MMP-2, MMP-9 mRNA and the activity of MMP-2, MMP-9 in the supernatant was inhibited significantly by A771726 (P＜0.01). The expression of CD147 mRNA was not inhibited significantly by A771726 (P＞0.05).Conclusion Leflunomide active metabolite (A771726) can inhibit the expression of PMA-induced CD147,MMP-2 and MMP-9 on THP-1 Cells.

Objective To investigate the role of recombinant Vibrio vulnificus cytolysin (rVvhA) in inducing THP-1 cells damage and study the pathway of associated calcium influx .Methods Inverted mi-croscope, CCK-8 cell proliferation kit, Fluo3/AM staining and caspase activity detection were performed to analyze the damage of THP-1 cells induced by rVvhA and the pathway of calcium influx .Results rVvhA had cytotoxic effects on THP-1 cells in a dose-dependent manner .The concentrations of extracellular K +and LDH were respectively up-regulated after 1 h and 6 h of 12 μg/ml rVvhA intervention .Verapamil , Mibe-fradil and SKF-96365 could not prevent the influx of free Ca 2+induced by rVvhA .The activities of caspase-3 and caspase-9 were singanificantly enhanced by rVvhA in a time-dependant manner .Conclusion rVvhA can induce THP-1 cells damage through triggering extracellular calcium influx via porous channel on cell membrane.Moreover, rVvhA might induce THP-1 cell apoptosis through activating caspase-9/3-dependent pathway .

Objective To observe the effect of infliximab combination therapy on the expression of CD147 on the peripheral CD14+ monocytes of active rheumatoid arthritis (RA) patients. Methods Thirty active RA patients who were refractory to MTX treatment were randomized into three groups (group A, B, C) with the proportion of 3:1:1. Group A and B received four or three infusions of infliximab (3 mg/kg), group C received four infusions of placebo. All three groups were added to a stable background of MTX. The mean fluorescence intensity (MFI) of CD147 expression on the peripheral CD14+ monocytes of RA patients and normal healthy controls were detected by flow cytometry analysis. Clinical and laboratory parameters were assessed before each infusion. One-way ANOVA, Kruskal-Wallis the MFI of CD147 expression at week 18 (P<0.05). Marked differences were observed between the infliximab + MTX group and the placebo + MTX group on the change of the MFI of CD147 expression from baseline to week 18 (P<0.05).Conclusion CD147 expression on the peripheral CD14+ monocytes of active RA patients is increased, and combination therapy of infliximab and MTX can inhibit the expression.

The aim of this study is to investigate the anti-inflammatory effect of the adenosine derivative N6-(3-hydroxylaniline) adenosine (WS070117M1) on cigarette smoke plus LPS (lipopolysaccharide)-induced chronic obstructive pulmonary disease (COPD) in mice and its mechanism. COPD model was established by exposing male BALB/c mice to cigarette smoke and challenged with LPS inhalation. Supernatants of bronchoalveolar lavage fluid (BALF) were harvested and IL-1β, IL-6, IL-8 and TGF-β1 levels were measured by ELISA (enzyme-linked immunesorbent assay). The number of total white blood cells and neutrophils in bronchoalveolar lavage fluid was counted separately. Lung tissue was stained with Mayer 's hematoxylin and eosin for histopathologic examination. pAMPKa protein expression and distribution of lung tissue were analyzed by immunohistochemistry method. In vitro, levels of AMPKα phosphorylation in phorbol-12- myristate-13-acetate (PMA) differentiated THP-1 cells was detected by immunohistochemistry, IL-8 level in supernatants of cigarette smoke condensate stimulating PMA differentiated THP-1 cells was measured by ELISA. The results showed that WS070117M1 treatment significantly activated AMPKa in the lung tissue. It also resulted in down regulation of IL-1β, IL-6, IL-8 and TGF-β1 levels in bronchoalveolar lavage fluid and IL-8 level in cigarette smoke condensate stimulating PMA differentiated THP-1 cells. In addition, WS070117M1 could inhibit the recruitment of total white blood cells and neutrophils. These results suggest that WS070117M1 may alleviate the airway inflammation by activating AMPK in the lung tissue.

A sensitive determination method for sulfur mustard ( HD ) metabolites thiodiglycol ( TDG ) in rabbit urine was established and validated using isotope dilution negative ion chemical ionization ( NICI) gas chromatography-mass spectrometry ( GC-MS ) , in which deuterated thiodiglycol ( TDG-d8 ) was used as internal standard. Two solid-phase extraction ( SPE) steps were established and optimized in order to reduce the interfering backgrounds, one was used to extract thiodiglycol ( TDG ) from urine with self-assemblied Florisil SPE cartridges, another cleaning treatment of the by-products after pentafluorobenzoyl chloride (PFBZ) derivatization. The results showed that the limits of detection quantitation of this method were 0. 1 and 0. 3 μg/L, respectively. The exposure time-response relationship and exposure dose-response relationship of TDG in rabbit urine were studied after rabbit skin exposure to sulfur mustard (HD, 0. 02-0. 15 LD50). The TDG levels in the rabbit urine increased rapidly during the first day after application and then decreased over time for all dosage groups. A secondary release was also noted for the high-dose group, and the duration of high TDG excretion levels was correlated positively with the HD dosage levels. We thus concluded that abnormally high levels of TDG in urine could be used as a clear diagnostic indicator of HD exposure.

End-stage renal disease (ESRD) is often complicated with damage of multi-organ function,among them,cognitive impairment has been noticed with a high prevalence.The abnormal intrinsic brain activity patterns in resting state is one of the manifestations of cognitive impairment in ESRD.Resting-state functional MRI (rs-fMRI) is divided into two categories,i.e.functional separation and functional integration,reflecting the changes of neural activity of the brain in different aspects.With advantages of non-invasive,no radiation and high spatio-temporal resolution,rs-fMRI has gradually become an effective method in studying the neurophysiological mechanisms of cognitive impairment.The pathophysiology and research progresses of rs-fMRI in ESRD with cognitive impairment were reviewed in this article.

Objective To investigate the changes of cerebral volume in end stage renal disease (ESRD) patients with maintaining hemodialysis using voxel based morphometry (VBM),and to observe the correlation of these changes with sleep quality,anxiety and depression.Methods Twenty ESRD patients received maintaining hemodialysis (patient group) and twenty-one normal volunteers (normal control group) underwent MRI and neuropsychological scale evaluations,including the Montreal Cognitive Assessment Scale (MoCA),Pittsburgh Sleep Quality Index Scale (PSQI),Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS).The changes of cerebral volume between the two groups were compared,and the correlation between the changed area of cerebral volume in patient group and the score of neuropsychological scale was analyzed.Results Compared with normal control group,significantly decreased volume in the gray matter of the left middle temporal gyrus,right middle frontal gyrus and left medial frontal gyrus were observed in patient group (all P＜0.001,AlphaSim multiple corrections).The differences of MoCA,PSQI,SAS and SDS between the two groups were statistically significant (all P＜0.05).In patient group,the decreased gray matter volume of the left middle temporal gyrus negativity correlated with PSQI,SDS and SAS (r=-0.588,-0.456,-0.489;P =0.006,0.043,0.029),of the right middle frontal gyrus negativity correlated with SDS and SAS (r=-0.495,-0.466;P=0.026,0.038),of the left medial frontal gyrus positively correlated with MoCA (r=0.462,P=0.040),and negatively correlated with PSQI (r=-0.588,P=0.006).Conclusion Multiple grey matter atrophy and complicated neurocognitive dysfunction were noticed in ESRD patients with maintaining hemodialysis,and the associated poorer sleep quality,anxiety or depression severity might closely related to the decreased volume of corresponding brain gray matter.

OBJECTIVETo assess the value of next generation sequencing (NGS) for the analysis of spontaneous abortion samples.

METHODSThe NGS analysis was carried out on 85 chorionic villi samples (taken between 42 days to 12 weeks of gestation) for which conventional cell culture has failed or chromosomal karyotyping has yielded normal or uncertain result.

RESULTSAmong 68 samples with a normal karyotype, the NGS analysis has identified 2 copy number variations (CNVs) and 2 chimeras. For 16 cases with failed cell culture, the NGS has identified 4 chromosomal abnormalities including 1 copy number variation and 3 numerical chromosomal aberrations. For 1 remaining case with uncertain karyotyping result, the NGS analysis has verified it as 46,XX,del(4) (p15.1p16.3).seq[GRCh37/hg19] (57 549 - 32 371 364)×1.

CONCLUSIONThe NGS analysis is capable of identifying novel CNVs in samples for which conventional cell culture may fail or karyotyping analysis may yield a normal result.

Abortion, Spontaneous ; genetics ; Adolescent ; Adult ; Cells, Cultured ; DNA Copy Number Variations ; Female ; High-Throughput Nucleotide Sequencing ; methods ; Humans ; Karyotyping ; Middle Aged ; Pregnancy ; Young Adult