抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Annales françaises d'anesthésie et de réanimation

The role of innate immunity in systemic lupus erythematosus (SLE) has been a rapidly expanding area of research over the last decade. Included in this rubric is the concept that activation of the inflammasome, a molecular complex that activates caspase-1 and in turn the cytokines IL-1β and IL-18, is important in lupus pathogenesis. This review will summarize the recent discoveries exploring the role of the inflammasome machinery in SLE.
Immune complexes can activate the NLRP3 inflammasome, and SLE-derived macrophages are hyper-responsive to innate immune stimuli, leading to enhanced activation of the inflammasome and production of inflammatory cytokines. Work in several murine models suggests an important role for the NLRP3 inflammasome in mediating lupus nephritis. Caspase-1, the central enzyme of the inflammasome, is essential for the development of type I interferon responses, autoantibody production, and nephritis in the pristane model of lupus. The absence of melanoma 2 inflammasome may have protective and pathogenic roles in SLE.
Recent evidence suggests that the inflammasome machinery is dysregulated in SLE, plays an important role in promotion of organ damage, and may mediate cross-talk between environmental triggers and the development of lupus. Further research should focus on whether inhibition of inflammasome components may serve as a viable target for therapeutic development in SLE.

The inflammasome and lupus: another innate immune mechanism contributing to disease pathogenesis?

The study of interactions between genome and exposome in the development of systemic lupus erythematosus.

Comprehensive review of genetic association studies and meta-analysis on miRNA polymorphisms and rheumatoid arthritis and systemic lupus erythematosus susceptibility.

Several confirmed genetic susceptibility loci involved in the interferon signaling and Th17/B cell response for SLE in Chinese Han populations have been described. Available data also indicate that sex-specific genetic differences contribute to SLE susceptibility. The aim of this study was to test for gene–gene/gene-sex epistasis (interactions) in these known lupus susceptibility loci. Six single-nucleotide polymorphisms (SNPs) in MiR146a, IRF5, IKZF1, ETS1 and IL21 were genotyped by Sequenom MassArray system. A total of 1,825 subjects (858 SLE patients and 967 controls) were included in the final analysis. Epistasis was tested by additive model, multiplicative model and multifactor dimensionality reduction (MDR) method. Additive interaction analysis revealed interactions between IRF5 and IKZF1 (OR 2.26, 95% CI 1.48–3.44 [P = 1.21×104]). A similar tendency was also observed between IL21 and ETS1 by parametric methods. In addition, multiple high dimensional gene-gene or gene-sex interactions (three-and four-way) were identified by MDR analysis. Our study identified novel gene–gene/gene-sex interactions in lupus. Furthermore, these findings highlight sex, interferon pathway, and Th17/B cells as important contributors to the pathogenesis of SLE.

/pdf/gene-gene-and-gene-sex-epistatic-interactions-of-mir146a-liyfu26ima.pdf

Gene-gene and gene-sex epistatic interactions of MiR146a, IRF5, IKZF1, ETS1 and IL21 in systemic lupus erythematosus.

The association of IL1α and IL1β polymorphisms with susceptibility to systemic lupus erythematosus: A meta-analysis

Genetic interaction between genes involved in NF-κB signaling pathway in systemic lupus erythematosus.

The catheter-related bladder discomfort (CRBD) of male patients is a common clinical problem, albeit lacking effective solutions. The present study aimed to investigate whether intravesical dexmedetomidine instillation alleviates the postoperative urinary discomfort in male patients with catheter under general anesthesia. This single-blinded, prospective, randomized study included a total of 167 male patients American Society of Anesthesiologists (ASA) physical status I-II scheduled for surgery under general anesthesia were allocated to two groups: 84 in the dexmedetomidine group and 83 in the control group. Dexmedetomidine group patients received intravesical instillation of the drug 0.5 μg/kg and normal saline 20 mL, while the control group received intravesical instillation of 20 mL normal saline. The catheter was clamped for 30 min after intravesical instillation for all patients. CRBD scores and urethra pain numerical rating scale (NRS) scores were measured at admittance to post-anesthesia care unit (PACU) (T0), intravesical instillation (T1), 30 min (T2), 60 min (T3), 2 h (T4) after intravesical instillation, discharged from PACU (T5), and 6 h (T6) and 24 h (T7) after the operation. Patient satisfaction at discharge from PACU and 24 h post-operation were compared between the two groups. CRBD scores and urethra pain NRS scores after 30 min of intravesical dexmedetomidine instillation to 24 h post-operation were significantly lower than the control group (p < 0.001), and patient satisfaction was higher at discharge from PACU and 24 h post-operation (p < 0.001). No differences were detected in Steward score out of PACU (p = 0.213) and from the time of the end of operation to fully awake (p = 0.417). Intravesical dexmedetomidine instillation reduces postoperative urinary discomfort and urethra pain and improves satisfaction in male patients under general anesthesia. Chinese Clinical Trial Registry (No. 
ChiCTR1800016429

), date of registration 1st June 2018.

/pdf/intravesical-dexmedetomidine-instillation-reduces-28dvaab755.pdf

Intravesical dexmedetomidine instillation reduces postoperative catheter-related bladder discomfort in male patients under general anesthesia: a randomized controlled study

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Gene-gene and gene-sex epistatic interactions of MiR146a, IRF5, IKZF1, ETS1 and IL21 in systemic lupus erythematosus.

The association of IL1α and IL1β polymorphisms with susceptibility to systemic lupus erythematosus: A meta-analysis

Genetic interaction between genes involved in NF-κB signaling pathway in systemic lupus erythematosus.

Intravesical dexmedetomidine instillation reduces postoperative catheter-related bladder discomfort in male patients under general anesthesia: a randomized controlled study