Effectiveness of Huai Qi Huang Granules on Juvenile Collagen-induced Arthritis and Its Influence on Pyroptosis Pathway in Synovial Tissue

Summary:Huai Qi Huang(HQH)exerts great effects in clinic,such as anti-inflammation,immune-regulation,anti-cancer,and so on.However,the mechanism by which HQH protects juvenile idiopathic arthritis(JIA)is obscure.Thus,we explored deeply the protective mechanisms in juvenile collagen-induced arthritis(CIA)rat model.Pyroptosis is Gasdermin D(GSDMD)-dependent programmed cell death,involved in many diseases,such as sepsis.We investigated whether GSDMD-induced pyroptosis take part in mechanisms of juvenile CIA arthritis.Juvenile Wistar rats(3-4 weeks)were injected intradermally with fully emulsified bovine typeⅡcollagen and complete Freund's adjuvant to establish CIA rat models.Later,the CIA rats received oral administration of HQH(4.16 g/kg)once a day from the day 21 of modeling,with the treatment lasting for 28 days.Varieties of indicators were measured for evaluation of anti-inflammation effect of HQH,including hind paw swelling,arthritis scores,micro CT,and histopathological changes and the level of pro-inflammatory cytokines in the serum,including tumor necrosis factor alpha(TNF-α)and interleukin-18(IL-18).The expression of GSDMD and caspasein the joint synovial tissues was detected.The results demonstrated that the expression of the pyroptotic protein GSDMD and its upstream caspase-1 was significantly increased in the synovial tissues of CIA rats.The treatment of HQH ameliorated the symptoms in CIA rats,reduced levels of pro-inflammatory cytokines and hind paw swelling,down-regulated the expression of GDSMD and caspase-1.GSDMDinduced pyroptosis participated in the pathogenesis of CIA rats.The study supported that HQH can effectively improve joints inflammation of juvenile collagen-induced arthritis rats by inhibiting pyroptosis pathway in the joint synovial tissues.

Effect of somatostatin analogue octreotide injected into the third cerebral ventricle on pentagastrin-induced gastric acid secretion in rats

AIM： To investigate the effect of long-lasting somatostatin analogue octreotide （Oct） injected into the third cerebral ventricle （TCV） on gastric acid secretion in rats. METHODS： TCVs were cannulated in male Wistar rats anesthetized with sodium pentobarbital. One week later acute gastric lumen perfusion was carried out and gastric acid was continuously washed with 37℃ saline by a perfusion pump. Gastric perfusion samples were collected every 10 min and titrated by 0.01 moL/L NaOH to neutral. On the basis of subcutaneous （sc） injection of pentagastrin （G-5, 160 μg/kg）, Oct （0.025 μg, 0.05 μg, 0.1 μg, n=12 in each group） or vehicle （pyrogen-free physiological saline, n = 10） was injected into the TCV, Before and after the TCV injection, 1 h total acid output （TAO） was determined and experimental data were expressed in change rate （%） of TAO. RESULTS： Oct （0.025, 0.05 and 0.1 μg） injected into the TCV resulted in change rate of 1.56% （P〉0.05）, 20.21% （P〈 0.01） and 37.82% of TAO （P〈 0.001）, respectively. Moreover, comparison in change rate of TAO among these 3 doses showed P〈 0.05 between 0.025μg and 0.05 μg, P〈 0.01 between 0.025 μg and 0.ling, and P〈 0.05 between 0.05μg and 0.1 μg. However, sc injection of 0.05 μg Oct had no effect on G-5 stimulated gastric acid secretion. CONCLUSION： Octreotide injected into the third cerebral ventricle inhibits gastrin-induced gastric acid secretion in a dose-dependent manner.

Serum Biomarkers for Early Diagnosis of Chinese X-CGD Children:Case Reports and a Literature Review

Since X-linked chronic granulomatosis disease(X-CGD)exhibits no specific clinical symptoms at an early stage,early diagnosis is difficult and depends predominantly on neonatal screening.Therefore,the aim of this study was to explore routine biomarkers for X-CGD in children and provide clues for early diagnosis.The cases of 10 children with X-CGD diagnosed at Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from 2013 to 2016 and 122 Chinese children with X-CGD reported in the literature were summarized.Serum biomarkers and clinical symptoms at acute infection were organized.A total of 132 children with X-CGD were enrolled in this study.For 55.8%of the patients,the diagnosis was delayed more than one year after the onset of the first symptoms because no typical clinical symptoms manifested.Children with X-CGD at an acute infection stage showed three recurrent signs in temis of serum biomarkers:(1)the total number of white blood cells(especially N%)was in creased significantly,accompanied by anemia in some cases;(2)C-reactive protein(CRP)levels were increased significantly;and(3)most of the patients exhibited very high serum IgG levels(>12 g/L).Diagnosis of X-CGD at an early age is difficult because of its nonspecific clinical features.Our study suggested children with X-CGD suffering acute infection show increases in three typical serum biomarkers,which can provide clues for early diagnosis.