To study the induced condition and characteristics of T cell anergy in vitro. Methods: Anergic Tcell was induced by combination of B7-1 mAb and cyclosporin A (CsA) in vitro, cytokine gene of anergic T cells was detected by RT-PCR. Results: T cell anergy was antigen-specific. The state of T cell anergy can be reversed by PHA, CD3 mAb and PMA plus A23187. IL-2 can prevent the induction of T cell anergy, but it can not reverse the state of un-responsiveness. IL-2 and IFN mRNA can not express in anergic T cells. In contrast, IL-4 and IL-10 mRNA were detectable. Conclusion: T cell anergy can be induced in vitro , cytokine profile of anergic T cells deviated to Th2-like phe-norype.

Objective To investigate the incidence of atherosclerotic renal artery stenosis (ARAS), the relationship between ARAS and cerebral artery stenosis, and the risk of ARAS in patients with brain infarction. Methods The clinical data of 1 650 brain infarction patients were analyzed, which were carried out digital subtraction angiography(DSA) of cerebral and renal artery.The incidence of ARAS was counted out, and the relationship was analyzed between the different degree and number of cerebral artery stenosis and the rate of RAS. The demographic characteristics and the common risk factors of atherosclerosis were recorded, and the risk factors of ARAS were analyzed. Results The rate of ARAS in moderate stenosis group and severe stenosis and occlusion group of cerebral artery were all significantly higher than that in mild stenosis group and no stenosis group (all P < 0.01). The rates of ARAS in severe stenosis and occlusion group were significantly significantly higher than those in moderate stenosis group (P < 0.01). The rates of ARAS in 2 branch stenosis group and ≥3 branch stenosis group were both significantly higher than those in no stenosis group and 1 branch stenosis group (P < 0.01). The rates of ARAS of ≥3 branch stenosis group were significantly higher than those in 2 branch stenosis group (P<0.05). The rate of ARAS of 1 branch stenosis group were significantly higher than those in no stenosis group (P < 0.05). Age, hypertension, moderate or more artery stenosis or occlusion, and≥2 branch stenosis was independent risk factor of ARAS. Conclusions The incidence of ARAS increasesd with the increase of the degree of cerebral artery stenosis and the number of branch involved.Older age, hypertension, moderate or more artery stenosis or occlusion, and≥2 branch stenosis is risk factor for ARAS.

ObjectiveTo evaluate prognosis and its clinical factors in patients with primary pontine hemorrhage. Methods Patients with primary pontine hemorrhage who were hospitalized in the First Affiliated Hospital of Wenzhou Medical College within 24 hours after stroke onset between April 2007 and April 2009 were registered conscutively. The patients were followed up for one year. Kaplan-Meier methods were used to analyze survival rate. Cox proportional hazards model was used to study risk factors for 1-year mortality. ResultsA total of 41 patients with primary pontine hemorrhage were studied. Their mean age was (63.5 ± 10. 1 ) years.The overall 1-year mortality rate was 61.0％, the median survival time was (80. 0 ±54.4) days (95％ CI 0-186. 64). After one-year follow-up, the mortality rate in patients with primary dorsal pontine hemorrhage( 18.2％ ) was significantly lower than that in patients with primary ventral pontine hemorrhage(72. 7％ ; x2 = 8. 800, P = 0. 003 ). Patients with massive primary pontine hemorrhage had significantly higher mortality rate than patients with dorsal primary pontine hemorrhage( x2 = 8. 927, P =0. 003). The average hematoma volume of the survivor group and mortality group was (3. 043 ± 1. 718) ml and (5. 984 ± 2. 707) ml, respectively, showing statistical significance (t = 3. 661, P = 0. 001 ). Analysis with Cox proportional hazards model showed that the risk factors associated with mortality were hematoma location ( RR = 2. 428, 95 ％ CI 1. 055-5. 587 ), hematoma volume ( RR = 1. 283, 95 ％ CI 1. 044-1. 577 ),GCS score on admission(RR =3. 389, 95％ CI 1. 177-9. 756). Patients with pontine hematomas in dorsal had a significantly better outcome than in other locations.Conclusions The survival and prognosis in primary dorsal pontine hemorrhage are better than with hemorrhaging in other parts of pontine. A significant correlation was observed between poor prognosis and hematoma volume, hematoma location and GCS score on admission.

YfiBNR is a recently identified bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) signaling system in opportunistic pathogens. It is a key regulator of biofilm formation, which is correlated with prolonged persistence of infection and antibiotic drug resistance. In response to cell stress, YfiB in the outer membrane can sequester the periplasmic protein YfiR, releasing its inhibition of YfiN on the inner membrane and thus provoking the diguanylate cyclase activity of YfiN to induce c-di-GMP production. However, the detailed regulatory mechanism remains elusive. Here, we report the crystal structures of YfiB alone and of an active mutant YfiB(L43P) complexed with YfiR with 2:2 stoichiometry. Structural analyses revealed that in contrast to the compact conformation of the dimeric YfiB alone, YfiB(L43P) adopts a stretched conformation allowing activated YfiB to penetrate the peptidoglycan (PG) layer and access YfiR. YfiB(L43P) shows a more compact PG-binding pocket and much higher PG binding affinity than wild-type YfiB, suggesting a tight correlation between PG binding and YfiB activation. In addition, our crystallographic analyses revealed that YfiR binds Vitamin B6 (VB6) or L-Trp at a YfiB-binding site and that both VB6 and L-Trp are able to reduce YfiB(L43P)-induced biofilm formation. Based on the structural and biochemical data, we propose an updated regulatory model of the YfiBNR system.
Amino Acid Sequence ; Bacterial Proteins ; chemistry ; genetics ; metabolism ; Binding Sites ; Biofilms ; Crystallography, X-Ray ; Cyclic GMP ; analogs & derivatives ; metabolism ; Dimerization ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Mutagenesis ; Protein Structure, Quaternary ; Pseudomonas aeruginosa ; metabolism ; Sequence Alignment ; Tryptophan ; chemistry ; metabolism ; Vitamin B 6 ; chemistry ; metabolism

The host takes use of pattern recognition receptors (PRRs) to defend against pathogen invasion or cellular damage. Among microorganism-associated molecular patterns detected by host PRRs, nucleic acids derived from bacteria or viruses are tightly supervised, providing a fundamental mechanism of host defense. Pathogenic DNAs are supposed to be detected by DNA sensors that induce the activation of NFκB or TBK1-IRF3 pathway. DNA sensor cGAS is widely expressed in innate immune cells and is a key sensor of invading DNAs in several cell types. cGAS binds to DNA, followed by a conformational change that allows the synthesis of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) from adenosine triphosphate and guanosine triphosphate. cGAMP is a strong activator of STING that can activate IRF3 and subsequent type I interferon production. Here we describe recent progresses in DNA sensors especially cGAS in the innate immune responses against pathogenic DNAs.
DNA, Bacterial ; immunology ; metabolism ; DNA, Viral ; immunology ; metabolism ; Gene Expression Regulation ; Host-Pathogen Interactions ; Humans ; Immunity, Innate ; Interferon Regulatory Factor-3 ; genetics ; immunology ; Interferon Type I ; biosynthesis ; immunology ; Membrane Proteins ; genetics ; immunology ; Models, Molecular ; NF-kappa B ; genetics ; immunology ; Nucleotides, Cyclic ; biosynthesis ; immunology ; Nucleotidyltransferases ; genetics ; immunology ; Protein Binding ; Protein-Serine-Threonine Kinases ; genetics ; immunology ; Signal Transduction