OBJECTIVEPsoriasis is an autoimmune-related chronic inflammatory skin disease strongly associated with the dysfunction of Th17 cells. Retinoic acid-related orphan nuclear receptor γt (RORγt) plays a critical role in the differentiation and maturation of Th17 cells and in cell-derived immunologic derangement. We conducted this study to investigate potential mechanism by which the derivative of digoxin selectively antagonizes RORγt transcriptional activity.

METHODUsing molecular docking in combination with molecular electrostatic potential (MEP), we detected the interaction between the derivative of digoxin (Dhd) and ROR transcription factor (RORα,RORβ and RORγt), and the results were further confirmed by bioluminescent assay.

RESULTMolecular docking demonstrated that Dhd could exclusively inhibit the conformation of RORγt; bioluminescent assay further indicated that RORγt was selectively antagonized by Dhd in a dose- and time-dependent manner.

CONCLUSIONDhd can selectively suppress RORγt transcriptional activity.

Digoxin ; analogs & derivatives ; pharmacology ; Humans ; Models, Chemical ; Molecular Docking Simulation ; Nuclear Receptor Subfamily 1, Group F, Member 1 ; antagonists & inhibitors ; genetics ; Transcription, Genetic

For the safety problems of internal medicine intravenous infusion,we carry out meticulous management,establish quality control system of intravenous infusion safety management,and formulate quality control plan.We collect and analyse the potential unsafety factors in the various departments of internal medicine.We have revised the intravenous infusion system and procedures,formulated standards for safety inspection of intravenous fluids,and standardized the admission system for nurses.We carry out training on intravenous infusion related knowledge for nursing staff,carry out meticulous management of venous transfusion links,and actively carry out learning and communication.All these measures have greatly enhanced the safety awareness of the nursing staff.The safety index of intravenous infusion for liver diseases was preliminarily summarized.The use rate of the safe indwelling needle was increased from 30.60％ to 92.30％,the rate of appropriate rate of drop speed increased from 68.45％ to 93.20％,the three sign standard rate rose from 75.20％ to 95.10％,and the patient's satisfaction with infusion increased from 85.60％ to 96.82％.Meticulous management can improve the safety of the internal medicine intravenous infusion as a whole.

Objective:To investigate the clinical phenotype and gene mutation in a child with developmental disorders caused by CTNNB1 gene mutation. Methods:Clinical data of a child with CTNNB1 gene mutation who was admitted to Xiamen Hospital of Fudan University Affiliated Pediatric Hospital in May 2017 were collected, whole exome sequencing technology was applied to verify the family lineage of the child, and the pathogenicity of mutation site was analyzed. Results:The patient was a 6 years and 1 month old male, with a clinical phenotype including mental retardation, motor developmental disorders, speech disorders, visual disorders (internal strabismus), microcephaly, and behavioral problems (social withdrawal, overdependence, etc.), as well as panic syndrome (i.e., sudden shrieking in response to auditory and visual stimuli, extensional rigidity of the body, etc., followed by short periods of general extensional rigidity). The whole exome sequencing results showed the presence of a de novo mutation c.283(exon4)C>T in the CTNNB1 gene, and the c.283(exon4)C>T mutation was interpreted as pathogenic (PVS1+PS2+PS1+PM2+PM) according to the American College of Medical Genetics and Genomics variant classification criteria and guidelines. No relevant genetic variants were found in the parental family verification. Conclusion:CTNNB1 gene mutation c.283(exon4)C>T can cause neurodevelopmental disorders, including mental retardation, motor developmental disorders, speech disorders, visual disorders, microcephaly and behavioral abnormalities.

Objective To study the brain functional connectivity(FC)changes in patients with normal tension glau-coma(NTG)and healthy volunteers using FC technique of resting-state functional magnetic resonance imaging(rs-fMRI)based on V1 region seed point(ROI),so as to explore the pathogenesis and early diagnosis of NTG.Methods Fourteen NTG patients(NTG group)who met the inclusion criteria and 14 healthy controls(HCs group)were enrolled.The clinical data of all subjects were collected,and rs-fMRI was performed in both groups.The magnetic resonance data was pre-pro-cessed by software,and bilateral A1 regions were taken as the ROI to analyze their correction with the whole brain voxel time series and obtain the FC value between the ROI and the whole brain by comparison of FC values in resting state be-tween the groups.Pearson correlation analysis was used to explore the relationship between FC value in the brain regions with significant differences with the ROI and clinical variables in the NTG group.Results Compared with the subjects in the HCs group,there were no statistically significant differences in age,gender,body weight,cup-disc ratio and 24 h mean intraocular pressure of patients in the NTG group(all P＞0.05),and there were statistically significant differences in the best corrected visual acuity(BCVA)of both eyes and peripapillary retinal nerve fiber layer thickness(RNFLT)(all P＜0.05).The Pearson correlation analysis showed that FC value of the brain regions with abnormal FC to V1 region were cor-related with RNFLT in the NTG group(P＜0.05).ROI1-left superior frontal gyrus,ROI1-right superior frontal gyrus,ROI2-left cingulate gyrus and ROI2-right middle frontal gyrus were significantly positively correlated with RNFLT(all P＜0.05).Compared with the HCs group,the brain regions with reduced FC to the right ROI in the NTG group were the left superior frontal gyrus and right superior frontal gyrus;the brain regions with reduced FC to the left ROI were the left cingulate gyrus and right middle frontal gyrus.Conclusion Compared to healthy individuals,NTG patients have significant changes in the functional connections between certain specific brain regions and V1 region,including bilateral superior frontal gyrus,left cingulate gyrus,and middle frontal gyrus.The changes in brain functional activity may be caused by visual dysfunction caused by NTG,leading to functional impairment of the visual and cognitive emotion processing brain regions,which may be one of the potential neuropathological mechanisms in NTG patients.

Objective To explore the changes in macular microcirculation status and visual function in patients with normal tension glaucoma(NTG)using the optical coherence tomography angiography(OCTA)and microperimeter MP-3 and analyze the correlation between the two.Methods In this cross-sectional observational study,17 NTG patients(30 eyes)were collected as the NTG group and then divided into mild,moderate and severe NTG subgroups according to the severity of the disease.During the same period,13 healthy subjects(23 eyes)with the same age and gender distribution were selected as the control group.OCTA was used to obtain linear density(LD)and perfusion density(PD)of superficial retinal vessels in the macular area.The microperimeter MP-3 was used to measure retinal sensitivity(RS)within 10° and fixation rate at 2° and 4° of the macular area.The OCTA parameters and microperimeter MP-3 parameters were compared among all groups,and the correlation between OCTA parameters and microperimeter MP-3 parameters in NTG patients was analyzed.Results There were no significant differences in LD and PD between the control group and the mild NTG sub-group in the central and nasal sides of the macula;the LD and PD in the remaining regions and overall average LD and PD showed a gradual downward trend in the control group and the mild,moderate and severe NTG subgroups.Compared with the control group,the RS of the mild NTG subgroup was lower in the inferior and temporal regions of the macular area.The RS of each region and overall average RS in the macular area decreased with the aggravation of the NTG.In the NTG group,LD and PD were significantly positively correlated with RS in each region and overall average RS in the macular area(all P＜0.05).In the NTG group,LD and PD were positively correlated with P2 in some regions of the macular area.Con-clusion Compared with the control group,the macular microcirculation status and visual function of NTG patients signif-icantly decreased with the progression of the disease;there is a significant correlation between macular LD and RS in NTG patients.