Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy

Objective:To analyze the clinical characteristics of pulmonary vein stenosis (PVS) in children, and to explore its treatment and prognostic factors.Methods:The clinical data of 19 children with PVS treated in Beijing Children′s Hospital, Capital Medical University from October 2016 to March 2022 were analyzed retrospectively.There were 16 males and 3 females.The median age at diagnosis was (2.81±1.95) years.A descriptive analysis of clinical characteristics of children was made.Results:Of the 19 children, 14 cases (73.7%) had primary PVS and 5 cases (26.3%) had secondary PVS after surgery of anomalous pulmonary venous connection (APVC). Thirteen children (68.4%) had hemoptysis.In the hemoptysis children, 5 cases had life-threatening massive hemoptysis, and 11 cases (57.9%) had a history of recurrent respiratory tract infection or pneumonia.Other manifestations of hemoptysis included failure to thrive (6 cases), cyanosis (5 cases), and dyspnea (3 cases). Complications were pulmonary hypertension (6 cases) and right heart failure (3 cases). There were 16 cases (84.2%) of unilateral PVS and 3 cases of bilateral PVS.Interlobular septal thickening, grid shadow and ground glass opacities were found on CT of all PVS cases.Ten cases underwent surgery, and 2 cases of them received angioplasty, but restenosis occurred in both of them.Eight children underwent pulmonary lobectomy, and their clinical symptoms were all relieved after operation.Nine patients were treated conservatively, and 3 cases of them died of bilateral PVS secondary to APVC.The remaining 6 alive cases still had intermittent clinical symptoms during follow-up.Conclusions:Hemoptysis and recurrent respiratory tract infection are the main clinical manifestations of PVS in children, and life-threatening massive hemoptysis can occur.Lobectomy is an effective treatment for unilateral PVS.The prognosis of secondary PVS after APVC is poorer and its mortality is higher, compared with primary PVS.

Objective:To analyze the clinical characteristics, treatment course and prognosis of children with intermediate-high risk pulmonary embolism.Methods:The clinical data of 48 children with pulmonary embolism treated in Beijing Children′s Hospital, Capital Medical University from January 2017 to December 2021 were analyzed retrospectively.Including 12 intermediate-high risk cases and 36 low-risk cases.The clinical manifestations, laboratory results, treatment and prognosis were compared between groups by the t-test, rank sum test and Chi- square test with the yates continuity correlation or Fisher′ s exact test. Results:There were no significant differences in the sex and age between the intermediate-high risk group and the low-risk group.The proportions of patients with shortness of breath, dyspnea, cyanosis or hypoxemia were higher in the intermediate-high risk group than those of in low-risk group.Twelve children in the low-risk group did not have specific symptoms of pulmonary embolism.There were no significant differences in the D-dimer level, and the distribution of pulmonary embolism between the two groups (all P>0.05). However, the proportion of children with other thromboembolism in the intermediate-high risk group was significantly higher than that of the low-risk group, among which heart thrombosis was the most common (7 cases). There were no significant differences in the underlying diseases and thrombophilia between the two groups (all P>0.05). The treatment of the intermediate-high risk group was more active: 6/12(50.00%) patients in the intermediate-high risk group received reperfusion treatment, including 3 cases of systemic thrombolysis, 1 case of catheter thrombolysis, and 2 cases of thrombectomy.In the low-risk group, only 1 case was treated with systematic thrombolysis.Unfavorable outcomes were reported in 3/48 (6.25%) patients, including 1 death of massive bleeding after catheter-directed thrombolysis in the acute phase, 1 case of recurrent pulmonary embolism after self-decided withdrawal and 1 case of progression of pulmonary embolism that was managed by surgical thrombectomy, all of whom were in the intermediate-high risk group. Conclusions:Shortness of breath, dyspnea, cyanosis or hypoxemia and co-existed venous thromboembolism were more common in intermediate-high risk cases.The treatment regimen of was more aggressive, but the incidence of unfavorable outcomes was higher in intermediate-high risk group; further research is needed to determine the risk factors for intermediate-high risk pulmonary embolism in children.

Objective:To analyze the clinical manifestations, genetic variations, diagnosis and treatment of children with inherited thrombophilia(IT).Methods:Retrospective study.Children with IT treated in Department of Respiratory Diseases 1 of Beijing Children′s Hospital, Capital Medical University from October 2016 to August 2021 were included in the study and followed up.Results:A total of 5 children met the inclusion criteria, with 3 boys and 2 girls; the age of diagnosis ranged from 7 years to 13 years and 6 months.There were 2 cases of protein C deficiency, 1 case of congenital protein S deficiency, 1 case of activated protein C resistance and 1 case of congenital afibrinogenemia.All 5 cases had pulmonary embolism, 2 cases had deep venous thrombosis of lower limbs, and 1 case had cardiac thrombosis and arterial embolism.The level of protein C was significantly decreased in 1 case, and the level of protein S in 1 case was significantly decreased in the laboratory test of thrombophilia; 2 cases were positive for antiphospholipid antibodies in the acute phase, but negative after 3-6 months of re-examination.Genetic analysis showed 2 cases of PROC gene mutation, 1 case of PROSI gene mutation, 1 case of F5 gene mutation, and 1 case of FGA gene mutation.All children were treated with anticoagulation drugs for long-term, including 4 patients with Warfarin and 1 patient with Rivaroxaban.The follow-up time ranged from 3 months to 5 years.During the follow-up, 1 patient experienced thrombosis recurrence due to infection incentives 1 month after discontinuing anticoagulant drugs on his own. Conclusions:The clinical manifestations of children with IT are the same as those of adults, mainly including venous thromboembolism(VTE); there are limitations in laboratory detection of thrombophilia, and gene analysis is of great significance.Children diagnosed with IT need long-term anticoagulant therapy to reduce the recurrence of VTE.

Objective:To describe the clinical features of pediatric biotinase deficiency (BTD) manifested as spinal cord disease.Methods:The clinical data of a child with spinal cord lesions due to biotinase deficiency, diagnosed in Beijing Children′s Hospital in 2020, were collected. The cases with complete clinical data retrieved on literature reported in China National Knowledge Infrastructure, Wanfang Data knowledge Service Platform and PubMed (up to August 2021) by using search terms of biotinase deficiency, pediatric, spinal cord, myelopathy and myelitis were summarized.Results:The patient was a 3 years and 5 months old boy with the main clinical manifestations of subacute progressive limb weakness and wheezing. Physical examination showed sparse hair, rough skin, spastic paraparesis and developmental delay. Cerebrospinal lactic acid was increased (5.67 mmol/L). Cranial magnetic resonance imaging (MRI) showed diffuse T 2/fluid attenuated inversion recovery hyperintensity of the midbrain, dorsal pons, edulla, periacqueductal grey and optic tracts. Spinal cord lesions were extended from the medulla up to the level of the conus. Urineketone bodies and 3-hydroxyisurate were increased. The activity of biotinidase was 0.27 pmol/min (3 mm disc), being 7% of mean normal serum activity. Genetic studies revealed homozygous mutation in the BTD gene [c.284T>A (p.I95N)]. After biotin supplementation for 6 months, the only evident abnormality was residual spasticity of lower limbs. Fourteen English literatures and 2 Chinese literatures including 18 cases were collected. The onset age was from 2 months to 15 years (median age was 4 years). Among them, 11 cases had cranial MRI abnormalities, of which all involved brain stem, 6 cases involved optic tracts and (or) optic chiasm. All 18 cases had spinal cord MRI abnormalities with longitudinally extensive lesion, mostly involved cervical and thoracic spinal segments, and 3 cases involved all spinal segments. Twelve cases received immunotherapy, and 6 were partially improved, 6 were completely invalid. After biotin supplementation, 12 patients had neurological disability. Conclusions:BTD should be included in the differential diagnosis of subacute myelopathy, regardless of the onset age. Early diagnosis and treatment can prevent irreversible neurological damage.

Objective:A case of cystic fibrosis admitted in the Respiratory Department of Beijing Children′s Hospital, Capital Medical University in June 2018 and underwent lung transplantation later was analyzed retrospectively.A 10-year-old girl had intermittent productive cough for more than 4 years with clubbed-finger.The lung high resolution CT (HRCT) showed bronchiectasis and mucus impaction, and the nasal sinus HRCT showed sinusitis.She had cystic fibrosis transmembrane conductance regulator ( CFTR) gene complex heterozygous mutation and positive sweat test.The immunoglobulin E (IgE) level and eosinophil count increased, and aspergillus fumigatus-specific IgE was positive.She was diagnosed as cystic fibrosis, allergic bronchopulmonary aspergillosis and sinusitis.Anti-infection, glucocorticoid and symptomatic treatment were given.During the following 21 months, the child had repeated respiratory difficulties and respiratory failure.Her lung function declined.Bilateral lung transplantation was performed in March 2020.She had a good recovery at more than 1 year and 3 months postoperatively.

Objective:To investigate the etiology of pleural effusion in hospitalized children in Beijing Children′s Hospital.Methods:Clinical information of children with pleural effusion admitted to Beijing Children′s Hospital Affiliated to Capital Medical University from January 2016 to December 2018 was retrospectively analyzed.According to the etiology, the children were divided into infection group (parapneumonic pleural effusion, tuberculous pleurisy and empyema) and non infection group.According to the age, the children were further divided into ≤ 3 years old, >3-7 years old and > 7 years old groups.Classification of statistics was performed, and the etiology of pleural effusion were retrospectively analyzed.Results:Among the 1 165 children with pleural effusion, 746 cases(64.0%) were infected with pleural effusion, 697 cases (697/746, 93.4%) of who were parapneumonic effusion.In patients with parapneumonic effusion, 457 cases (61.3%) had Mycoplasma pneumonia (MP) infection.Infectious pleural effusion was more common in children >7 years old(339/479 cases, 70.8%), while non-infectious pleural effusion was prevalent in children under 3 years old(188/324 cases, 58.0%). The difference was statistically significant ( χ2=96.33, P<0.05). Among the patients with non-infectious pleural effusion, 239 cases (239/419 cases, 57.0%) had multi-system diseases and 97 cases (97/419 cases, 23.2%) had malignant pleural effusion.All the 18 deaths were non-infectious pleural effusion. Conclusions:The leading reason for pleural effusion in children is infection.The most prevalent symptom is parapneumonic effusion, which is mainly caused by MP.

Respiratory support is the treatment of respiratory diseases.Currently, the commonly used methods of respiratory support include nasal catheter oxygen or mask oxygen, noninvasive and invasive ventilation, etc.High flow nasal cannula oxygen (HFNC) is a new kind of therapy, which was commonly used in preterm infants as the instead of continuous positive airway pressure (CPAP). However, in recent years, HFNC is more commonly used in children′s intensive care unit and general wards.In this paper, the efficacy and safety of HFNC in pediatric are reviewed.

Objective To explore the diagnosis and treatment of atypical severe combined immunodeficiency disease (SCID). Methods The clinical data of atypical SCID in 7 children with IL2RG,JAK3,and RAG1 mutations were reviewed and analyzed from September 2012 to June 2017. Results In 7 cases (6 males and 1 female), there were 5 infants, 1 toddler and 1 school-age child. Cases 2, 4, and 6 were classic SCID clinical phenotypes. Cases 1, 3, 5, 7 were atypical SCID clinical phenotypes. Case 6 were diagnosed with Omenn syndrome. Cases 2, 5 were classic SCID immune phenotypes, cases 1, 3, 4, 6, 7 were atypical SCID immune phenotypes, and case 1 had maternal chimera. The next generation sequencing indicated that case 1 had a compound heterozygous JAK3 mutation with c.3097-1G>A/c.946-950GCGGA>ACinsGGT.Cases 2,3,and 4 had IL2RG mutations,with c.865C>T/p.R289X,c.664C>T/R222C,52delG,respectively.Case 5 had JAK3 mutations with c.2150A>G/p.E717G and c.1915-2A>G.Sanger sequencing indicated that case 6 had a RAG1 mutation of complex heterozygosity with c.994C>T/p.R332X and c.1439G>A/p.S480N. Case 7 had homozygous RAG1 mutation with c.2095C>T/p.R699W.Conclusion Under certain conditions,gene mutation can lead to atypical clinical and/or immune phenotypic SCID.

Many different types of neuromuscular disorders can affect respiratory function by either a muscle itself or the nerve(s) supplying that muscle.Patients with certain inherited neuromuscular diseases,such as spinal muscular atrophy,spinal muscular atrophy with respiratory distress type 1,SEPNl-related myopathies,can present with recurrent respiratory system infections,acute or chronic respiratory failure as well as sleep disordered breathing.The respiratory complications could show up even before the manifestation of neuromuscular diseases.The chest X-ray,blood gas analysis,spirometry,sleep studies etc can be used to assess the affected respiratory muscle function,and also can be used to prove the suspicion of the neuromuscular disorders.