Inhibition of GSDMD-mediated pyroptosis triggered by Trichinella spiralis intervention contributes to the alleviation of DSS-induced ulcerative colitis in mice.

BACKGROUND: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing worldwide. Although there is currently no completely curative treatment, helminthic therapy shows certain therapeutic potential for UC. Many studies have found that Trichinella spiralis (T.s) has a protective effect on UC, but the specific mechanism is still unclear. METHODS: Balb/c mice drank dextran sulfate sodium (DSS) to induce acute colitis and then were treated with T.s. In vitro experiments, the LPS combination with ATP was used to induce the pyroptosis model, followed by intervention with crude protein from T.s (T.s cp). Additionally, the pyroptosis agonist of NSC or the pyroptosis inhibitor vx-765 was added to intervene to explore the role of pyroptosis in DSS-induced acute colitis. The degree of pyroptosis was evaluated by western blot, qPCR and IHC, etc., in vivo and in vitro. RESULTS: T.s intervention significantly inhibited NLRP3 inflammasome activation and GSDMD-mediated pyroptosis by downregulating the expression of pyroptosis-related signatures in vitro (cellular inflammatory model) and in vivo (DSS-induced UC mice model). Furthermore, blockade of GSDMD-mediated pyroptosis by the caspase-1 inhibitor vx-765 has a similar therapeutic effect on DSS-induced UC mice with T.s intervention, thus indicating that T.s intervention alleviated DSS-induced UC in mice by inhibiting GSDMD-mediated pyroptosis. CONCLUSION: This study showed that T.s could alleviate the pathological severity UC via GSDMD-mediated pyroptosis, and it provides new insight into the mechanistic study and application of helminths in treating colitis.

Epitope vaccine design for Toxoplasma gondii based on a genome-wide database of membrane proteins.

BACKGROUND: There is presently no effective and safe vaccine for Toxoplasma gondii for humans. The study described here was designed to search for a novel group of optimal B cell and T cell epitopes from Toxoplasma membrane proteins using genome-wide comprehensive screening. METHODS: The amino acid sequences of membrane proteins of T. gondii were obtained from the UniProt database. The ABCPred and BepiPred servers were employed to predict the linear B cell epitopes. The Immune Epitope Database (IEDB) online service was utilized to forecast T cell epitopes within T. gondii membrane proteins that bind to human leukocyte antigen (HLA) class I (HLA-I) or HLA-II molecules. RESULTS: From the 314 membrane proteins of T. gondii, a total of 14 linear B cell epitopes embedded in 12 membrane proteins were identified. Eight epitopes for major histocompatibility complex (MHC) class I (MHC-I) molecules and 18 epitopes for MHC-II molecules were ultimately selected, for which world population coverage percentiles were 71.94% and 99.76%, respectively. The top rated combinations of linear B cell epitopes and T cell epitopes covering both BALB/c mice and a majority of the human population were identified for the development of a protective vaccine. CONCLUSIONS: The ultimate vaccine construct described here, which comprises B cells, MHC-I and MHC-II epitopes, might protect individuals against T. gondii infection by inducing humoral and cellular immune responses.

[Clinical features of neuroendocrine cell hyperplasia of infancy].

OBJECTIVE: To study the clinical features of neuroendocrine cell hyperplasia of infancy (NEHI) in order to provide a basis for the management of diagnosis, treatment and prognosis of children with NEHI. METHODS: A retrospective analysis was performed for the clinical data of seven children with NEHI who were diagnosed and treated from January 2014 to March 2016. RESULTS: Among the seven children with NEHI, there were five boys and two girls. Two children experienced tachypnea since the neonatal period, and five children developed respiratory tract symptoms within 1-6 months after birth. Of the 7 children, 6 had pulmonary crackles, 4 had hypoxemia, and 3 had gastroesophageal reflux. Lung high-resolution CT (HRCT) showed ground-glass opacities in the central region of the lungs in all children, which involved at least two lung lobes. Of the 7 children, 2 had the involvement of more than 4 lobes and 6 had air trapping. All 7 children had an improvement in clinical symptoms after two years of age. One child achieved clinical and CT remission. Four children achieved clinical remission, but still with CT changes. CONCLUSIONS: NEHI often occurs in infancy, with the major clinical manifestations of persistent tachypnea, pulmonary crackles, and hypoxemia. The children with NEHI often present ground-glass opacities in the central region of the lungs and air trapping on HRCT. There is no specific treatment for this disease and most cases have a good prognosis.

[Painless skin nodules and ecchymosis in a school-aged girl].

A 7-year-old girl was admitted to Xiangya Hospital due to systemic lymphadenectasis for 2 months and skin ecchymosis for 3 days. Nine months ago, the girl experienced painless nodules in the left lower extremity with no apparent causes. Three months later, dermatorrhagia and ecchymosis occurred in many regions such as the periocular areas, conjunctiva, oral mucosa, perineal area, and groin, with a "raccoon sign" in both eyes; superficial lymphadenectasis and hepatosplenomegaly were also observed in many regions. The pathological sections for the skin nodules showed malignant tumors in lymphohematopoietic cells, and in combination with clinical manifestations, immunohistochemistry, and positive results for CD4, CD56, and CD123 by bone marrow flow cytometry, the girl was diagnosed with blastic plasmacytoid dendritic cell neoplasm. Then high-risk ALL regimen was applied as the chemotherapy for this girl. At present, the girl has been followed up for 3 months; ecchymosis has disappeared, and the enlarged lymph nodes have shrunk. No abnormal cells have been found in bone marrow morphological examination, and bone marrow flow cytometry has shown that primitive precursor cells account for 1.5% and express CD33, CD34, CD123, and CD117.

[An improved method of electrode placement for ECG monitoring in children].

OBJECTIVE: This study examines the impacts of an improved electrode placement on the electrocardiogram (ECG) results in order to determine a better electrode placement for ECG monitoring in children. METHODS: ECG was recorded using the traditional electrode placement and the modified electrode placement (with shortened electrode distance) respectively in 50 pediatric patients. The amplitudes of P wave and QRS wave on ECG by the two measurements were compared. Furthermore, the impacts of different body positions on the amplitudes of P wave and QRS wave were studied after applying the modified electrode placement. RESULTS: There were no significant differences in the amplitudes of P wave and QRS wave on ECG by the traditional electrode placement and the modified electrode placement (P>0.05). When modified electrode placement was utilized, the body position change did not lead to significant changes in the amplitudes of P wave and QRS wave (P>0.05). CONCLUSIONS: A satisfactory ECG can be obtained with the modified electrode placement independent of patient's body position, suggesting that the modified electrode placement can be used instead of the traditional placement in children.