Haploinsufficiency of A20 caused by a novel pathogenic missense variant of TNFAIP3 and successfully treated with anti-TNF and immunosuppressive therapies.

Loss-of-function of protein A20, encoded by TNFAIP3, leads to an early-onset haploinsufficiency of A20 (HA20). This study reports one Chinese child with HA20 and explores the genetic etiology of TNFAIP3 variant. The patient exhibited transient recurrent episodes of fever, intermittent signs of arthritis, gastrointestinal symptoms and multiple colonic ulcers. Laboratory tests revealed elevated inflammatory indicators and mild to moderate anemia. Genetic analysis identified a heterozygous de novo variant in his TNFAIP3 gene (c.740C＞T, p. P247L), which had never been reported before. The novel missense variation was validated to be pathogenic through causing insufficient expression of A20, over-activation of NF-κB signaling pathway and elevated levels of proinflammatory cytokines in response to stimulation by lipopolysaccharide. A combination of oral corticosteroids, TNF-α inhibitors and thalidomide freed him from symptoms and abnormal inflammatory indicators. Furthermore, continual improvement of the patient's condition was observed during a follow-up period of five months. We demonstrate a case with a de novo missense variant resulting in a loss-of-function of TNFAIP3, which expands the clinical spectrum of HA20. Cytokine antagonists and immunosuppressants may be effective drugs.

Anti-cisplatin-induced Renal-injury Effect of Human Manganese Superoxide Dismutase with Leader Peptide / 肿瘤防治研究

Objective To investigate the effect of the fusion of leader peptide on the structure of human manganese superoxide dismutase (SOD2) and anti-cisplatin (DDP)-induced renal injury. Methods The effect of mitochondrion targeting sequence (MTS) on the structure and activity of SOD2 was analyzed by structure prediction and superoxide dismutase (SOD) specific-activity determination. The DDP injury model of Kunming (KM) mice was established, and amifostine (AMFT) was set as a positive control. Indicators such as kidney index, renal function, kidney antioxidant capacity, and appearance and pathology changes of mice kidney were used to evaluate the effect of MTS-SOD2 against DDP-induced kidney injury. Results The MTS leader peptide seemed to change the secondary and tertiary structures of SOD2 to some extent, but it also increased the specific activity of the MTS-SOD2 protein. Pre-administration of a medium dose of MTS-SOD2 (0.84 mg/kg) before the use of DDP significantly reduced the level of renal malondialdehyde and increased the SOD activity and total antioxidant capacity (T-AOC) in the kidney, thereby reducing the renal pathological damage and consequently maintaining renal function. The overall protective effect of MTS-SOD2 was comparable to or even better than that of 200 mg/kg AMFT. Conclusion The MTS leader peptide enhances the activity of SOD2 and confers it with an excellent anti-DDP-induced renal-injury effect because of its transmembrane function.

Study on quality standard of Ershiwuwei-Shanhu pill / 国际中医中药杂志

Objective This paper is intended for establishing quality standard of Ershiwuwei Shanhu pill. Methods The TLC was used to indentify Pyrethrum tatsienense, Sesami nigrum semen, Aquilariae lignum resinatum, Caryophmlli flos, Acori calami rhizoma, Chebulae fructus, Aucklandiae radix and Glycyrrhizae radix et rhizome. For hydroxysafflor yellow A, the HPLC system consisted of WondaSil-C18 (250 mm×4.6 mm, 5μm), methanol-acetonitrile- 0.7% phosphoric acid (26:2:72) as mobile phase, flow rate of 1.0 ml/min, detection wavelength at 403 nm. For liquiritin, the HPLC system consisted of WondaSil-C18 (250 mm×4.6 mm, 5μm), acetonitrile (A)-0.05% phosphoric acid (B) as mobile phase, flow rate of 1.0 ml/min, detection wavelength at 237 nm. And for crocin-I, the HPLC system consisted of WondaSil-C18 (250 mm×4.6 mm, 5μm), methanol-water (49:51) as mobile phase, flow rate of 1.0 ml/min, detection wavelength at 440 nm. Results The methods of TLC were simple with strong specificity and good reproducibility. The results of HPLC showed that calibration curve was linear in the ranges of 0.046 7-0.233 8μg for hydroxysafflor yellow A, and 0.510 6-1.531 8μg for liquiritin and 0.048 1-0.340 5μg for crocin-I. The average recovery rate was 102.01%, 99.50%and 99.32%, respectively. Conclusion The new method is more appropriate for the quality control of Ershiwuwei Shanhu pill.

Genotype, environment and their interactions of major bioactive components in 2-year licorice (Glycyrrhiza uralensis) population / 中国中药杂志

<p><b>OBJECTIVE</b>This study aimed at analyzing the effect of genotype (G), environment (E) and their interactions (G x E) on the major bioactive components of 2-year licorice (Glycyrrhiza uralensis) population, in order to provide a theoretical basis for the licorice breeding with high content of bioactive components and quality improvement.</p><p><b>METHOD</b>Four genotype licorice populations were transplanted under four different environments by using complete randomized block design with three replicates, and four major bioactive components, including glycyrrhizin (GL), total saponins (TS), liquiritin (LQ) and total flavonoids (TF) were determined by UV and by HPLC.</p><p><b>RESULT</b>The major bioactive components of licorice were influenced by genotype and environment, and the genotype had more effect on all of the bioactive components. The contents of GL and LQ were codetermined by genotype and environment factors.</p><p><b>CONCLUSION</b>There exist different selective effects on different growth region for quality breeding in cultivated population of licorice.</p>