Objective To investigate the therapeutic mechanism of Pterocarya hupehensis Skan total flavonoids(PHSTF)for rheumatoid arthritis(RA).Methods Twenty-five male SD rats were randomly divided into normal control group,RA model group,PHSTF treatment(45 and 90 mg/kg)groups,and Tripterygium glycosides(TPG)tablet(10 mg/kg)group(n=5).Except for those in the normal control group,all the rats were subjected to collagen-induced arthritis(CIA)modeling using a secondary immunization method,after which PHSTF and TPG were administered via gavage once daily for 4 weeks.After the treatments,serum levels of TNF-α and IL-1β were measured using ELISA,and ankle joint pathologies were assessed with HE staining;the expression of citrullinated histone H3(Cit-H3),a neutrophil extracellular trap(NET)marker,in the ankle joints was evaluated with immunohistochemistry.In primary cultures of rat peripheral blood neutrophils stimulated with phorbol ester(PMA),the effects of PHSTF(100 and 200 μg/mL)on the expressions of Cit-H3,peptidylarginine deiminase 4(PADI4),neutrophil elastase(NE),and myeloperoxidase(MPO)were examined with Western blotting;immunofluorescence assay was used to observe Cit-H3 expression and NET formation in the cells.Results In the CIA rat models,PHSTF significantly alleviated ankle swelling,decreased serum levels of TNF-α and IL-1β,improved histopathological changes in the ankle joints,and reduced Cit-H3 expression in both the serum and ankle joint cartilage.In the isolated rat neutrophils,PHSTF showed no significant effect on cell viability but strongly inhibited PMA-induced NET release.Conclusion PHSTF can alleviate RA by inhibiting the formation of NETs.

Objective To investigate the therapeutic mechanism of Pterocarya hupehensis Skan total flavonoids(PHSTF)for rheumatoid arthritis(RA).Methods Twenty-five male SD rats were randomly divided into normal control group,RA model group,PHSTF treatment(45 and 90 mg/kg)groups,and Tripterygium glycosides(TPG)tablet(10 mg/kg)group(n=5).Except for those in the normal control group,all the rats were subjected to collagen-induced arthritis(CIA)modeling using a secondary immunization method,after which PHSTF and TPG were administered via gavage once daily for 4 weeks.After the treatments,serum levels of TNF-α and IL-1β were measured using ELISA,and ankle joint pathologies were assessed with HE staining;the expression of citrullinated histone H3(Cit-H3),a neutrophil extracellular trap(NET)marker,in the ankle joints was evaluated with immunohistochemistry.In primary cultures of rat peripheral blood neutrophils stimulated with phorbol ester(PMA),the effects of PHSTF(100 and 200 μg/mL)on the expressions of Cit-H3,peptidylarginine deiminase 4(PADI4),neutrophil elastase(NE),and myeloperoxidase(MPO)were examined with Western blotting;immunofluorescence assay was used to observe Cit-H3 expression and NET formation in the cells.Results In the CIA rat models,PHSTF significantly alleviated ankle swelling,decreased serum levels of TNF-α and IL-1β,improved histopathological changes in the ankle joints,and reduced Cit-H3 expression in both the serum and ankle joint cartilage.In the isolated rat neutrophils,PHSTF showed no significant effect on cell viability but strongly inhibited PMA-induced NET release.Conclusion PHSTF can alleviate RA by inhibiting the formation of NETs.

Objective:To explore the association between chest high resolution CT (HRCT) scoring and prognostic factors of interstitial lung disease (ILD) in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM).Methods:The patients with DM admitted to Kailuan General Hospital between January 2017 and December 2019 were included into the study including 13 patients with positiveanti-MDA5 antibody (7 survivors, 6 deaths) and 18 patients with anti-synthase (ARS)-antibody positive. All patients underwent chest HRCT prior to treatment. The consolidation, ground-glass opacity (GGO) and fibrosis were scored to assess HRCT findings. The clinical manifestations were compared between the two groups. Cox regression analysis adjusted for age and sex was used to determine the prognostic factors for anti-MDA5 antibody-related ILD.Results:Compared with ARS patients, glutamyl transferase (GGT) and ferritin levels were significantly higher in MDA5-ILD patients [70.0(37.0, 122.5) vs 21.0(16.5, 33.5), Z=-3.37, P=0.001; 977.0(502.5, 1 366.0) vs 307.1(72.3, 546.9) , Z=-3.44, P=0.001]. The cumulative survival rate was significantly lower in patients with positive anti-MDA5 antibody than in those with positive anti-ARS antibody (100% vs 70%, P=0.001). The DM complicated with acute/subacute interstitial pneumonia (A/SIP) were found to significantly relate to death. There were no significant differences in chest HRCT scoringbetween the survivors and the deceased patients [ HR=1.08, 95% CI(0.95, 1.23), P=0.229; HR=0.97, 95% CI(0.72, 1.30), P=0.814]. Conclusion:Anti-MDA5 antibody is an important index for early diagnosis of DM complicated with acute/subacute interstitial pneumonia (A/SIP). The chest HRCT scoreis is not associated with the prognosis of anti-MDA5 antibody-related ILD patients.

The epidemic of COVID-19 has become the topmost public health threat worldwide. The authors suggested that in addition to strengthening the organization and leadership of the abovementioned work, greater attention be paid to establishing and improving the prevention and control mechanism.Furthermore, special efforts should be given to the safety of the medical workers, by strengthening their infection monitoring and outbreak management. Medical workers in different work areas and positions should be placed under careful protection with due cleaning and disinfection measures. The protection during specimen collection, transportation and medical waste management should also be prioritized. Such special issues in the management of pediatric patients, as allocation of nurses, the screening and management of caregivers, the problem of breastfeeding, and the disinfection of children′s toys and diapers were discussed. This paper also put forward management suggestions for the outpatient department, isolation ward and other key departments, which aim to guide the prevention and control of COVID-19 nosocomial infection in the pediatric outpatient and ward.

OBJECTIVE: To analyze the molecular etiology of a Chinese child affected with dihydropyrimidinase deficiency. METHODS: Genomic DNA was extracted from peripheral blood samples of the family members. Pathogenic variant was determined by whole exome sequencing and verified by Sanger sequencing. RESULTS: The child was found to harbor homozygous c.905G>A (p.Arg302Gln) variants in exon 5 of the DPYS gene, for which her parents were both heterozygous carriers. CONCLUSION The homozygous c.905G>A (p.Arg302Gln) variants of the DPYS gene probably underlies the dihydropyrimidinase deficiency in the child. Above result has enabled genetic counseling and prenatal diagnosis for this family.
Amidohydrolases/genetics* ; Asian Continental Ancestry Group/genetics* ; Child ; Exons ; Female ; Humans ; Metabolism, Inborn Errors/genetics* ; Mutation ; Pedigree

The pneumonia caused by the novel coronavirus (2019-nCoV), which began in December 2019, has become the most serious public health problem, threatening people's health and life. This threat is posing a severe challenge on the diagnosis and treatment of 2019-nCoV infection, the prevention and control of hospital cross infection of medical staff. It is suggested that in addition to strengthening the organization and leadership of the abovementioned work, establishing and improving the prevention and control mechanism deserve greater attention. Furthermore, special attention should be given to the safety of the medical staff, strengthening their infection monitoring and outbreak management. Medical staff in different work areas and positions should be placed under careful protection, cleaning and disinfection measures. The protection during specimen collection, transportation and medical waste management should also be prioritized. This paper also put forward management suggestions for the outpatient department, isolation ward and other key departments. These measures are proposed to provide a guidance for the prevention and control of 2019-nCoV nosocomial infection in the pediatric outpatient and ward.

OBJECTIVE: To carry out genetic testing for two families affected with cobalamin C (cblC) and establish a rapid method for the detection of a hotspot pathogenic variant c.609G>A of the MMACHC gene by using a PCR-high-resolution melting curve (PCR-HRM) method. METHODS: Genomic DNA was extracted from peripheral blood samples of the probands and their parents. Potential variants of the MMACHC gene was analyzed by Sanger sequencing. The c.609G>A variant of the MMACHC gene was screened among 100 healthy children with the PCR-HRM method. RESULTS: Sanger sequencing revealed that proband 1 carried compound heterozygous variants c.394C>T and c.609G>A of the MMACHC gene, while proband 2 carried compound heterozygous variants c.482G>A and c.609G>A of the same gene. PCR-HRM analysis of the two probands and the 100 healthy children were consistent with the Sanger sequencing. CONCLUSION c.609G>A is a hotspot pathogenic variant of the MMACHC gene. The diagnosis of cblC may be rapidly attained through detection by PCR-HRM.

OBJECTIVE: To explore the genetic basis for a child with dihydropyrimidase (DHP) deficiency. METHODS: High-throughput sequencing was carried out for the child. Suspected variants were verified by using Sanger sequencing. RESULTS: The proband was found to carry compound heterozygous variants of the DPYS gene, namely c.1468C>T (a missense variant) and c.1339-1363del (a frameshifting variant). CONCLUSION The compound heterozygous variants of the DPYS gene probably underlie the DHP in this child. Above result has enabled genetic counseling and prenatal diagnosis for his parents.

Objective: To study the clinical and laboratory diagnosis and follow-up of 4-hydroxy butyrate aciduria in children. Methods: From June 2012 to July 2017, 9 cases in Tianjin Children′s Hospital were analyzed.According to their clinical features, multidimensional analysis was performed by using head magnetic resonance imaging (MRI), urine gas chromatography-mass spectrometry (GC/MS) semi-quantitative testing and gene mutation analysis of ALDH5A1. Results: The onset age of the 9 cases was less than 1 year old, and all had psychomotor retardation, in which 4 cases with epileptic seizures, 1 case with consciousness disturbance and 1 case with involuntary movement.All the cases underwent head MRI and 4 cases showed bilateral symmetry pallidal lesions, including 1 case with symmetry abnormality of the midbrain cerebral peduncle, 1 case with encephalomalacia in left temporal cortex and 4 cases with widening of the ventricle and extracerebral space.By the urine GC/MS semi-quantitative testing, all 9 the cases showed increasing 4-hydroxy butyric acid and by the ALDH5A1 gene mutation analysis, all 9 the cases were detected with gene mutation (3 cases belonging to c. 1568C>T homozygous mutation, 1 case belonging to c. 839T>G homozygous mutation and the other 5 cases belonging to compound heterozygous mutation, which included c. 691G>A, c.1568C>T; c.1383_2delA, c.1568C>T; c.527G>A, c.691G>A; c.904G>A, c.1022C>A; c.398_399delA, c.638G>T). Nine cases were given symptomatic treatment, and 4 cases with epileptic seizures were given antiepileptic drugs.During the follow-up of the above 9 cases, 1 case died of status epilepticus, 1 case had been under control for 5 years, and 2 cases were effectively treated.Psychomotor retardation was improved in varying degrees in 8 cases.Involuntary movement disappeared in 1 case while 2 cases still showed increasing 4-hydroxy butyric acid by means of urine GC/MS semi-quantitative testing. Conclusions Most of 4-hydroxy butyrate aciduria occurs within 1 year old, with psychomotor development as the first manifestation, which can be associated with epilepsy.The head MRI is characte-rized by a symmetrical Globus pallid abnormal signal.Urine GC/MS shows an increase in 4-hydroxy butyrate, which is the basis for biochemical diagnosis of the disease.Its accumulation in the body mainly damages the central nervous system.ALDH5A1 is a disease-causing gene, in which c. 1568C>T site has a high mutation frequency, and it is speculated that this site may be a hot spot mutation in Chinese children.Patients with epilepsy may die from status epilepticus and may be used as a clinical indicator to judge the severity of the disease.There is no specific treatment, and the patients combined with epilepsy can be treated with anti-epileptic drugs.Valproic acid should be avoided as it can aggravate the condition.

Objective To investigate the correlation between cumulative serum uric acid (cumUA) and brachial-ankle pulse wave velocity (baPWV).Methods Among the workers who participated in the four health check-up of Kailuan Group from 2010 to 2017,subjects who completed one PWV test were selected.The subjects who met the selection criteria were 20 688,subjects who lacked the first three uric acid tests and sex data were excluded.The subjects who had ischemic stroke (excluding lacunar infarction),transient ischemic attack and myocardial infarction were excluded.Decreased subjects were excluded and the extreme value were also excluded,20 295 subjects eventually meet the inclusion criteria and were included for statistical analysis.Stepwise linear regression,multivariate logistic regression and natural spline function were used to analyze the relationship between cumUA and baPWV and the influence of cumUA on baPWV.Results Among 20 295 subjects,the incidence of baPWV ≥ 14 m/s (criteria for judging atherosclerosis) increased with the increase of cumUA.There was significant difference in the incidence of baPWV ≥ 14 m/s (53.07％,54.35％,56.42％,58.41％,61.91％) among different cumUA partition groups (β=0.11,P＜0.01).In stepwise linear regression analysis,after adjusting for other confounding factors,it was found that cumUA was positively correlated with baPWV.In multivariate logistic regression analysis,after adjusting for other confounding factors,the results showed that baPWV ≥aPWVm were all risk factors for the third,fourth and fifth subgroups of cumUA compared with the first subgroup,and the OR05％CI) was 1.35(1.13,1.62) (P=0.01),1.60(1.29,1.97) (P＜0.01) and 2.14(1.64,2.80) (P＜0.01),respectively.Natural spline analysis exhibited a similar J curve relationship between cumUA and increased baPWV.Conclusion CumUA is a risk factor for increased baPWV.