Role of surfactant protein C in neonatal genetic disorders of the surfactant system: A case report.

RATIONALE: Respiratory distress syndrome (RDS) refers to the symptoms of progressive dyspnea and respiratory failure in newborns shortly after birth. The clinical and genetic characteristics of patients with neonatal RDS have not been extensively reported. PATIENT CONCERNS: A infant was in critical condition with repeated paroxysmal blood oxygen decline. Oxygen inhalation and noninvasive ventilator-assisted breathing relief were not effective. The etiology was unclear, and there was no family history of lung disease. Surface-active substance replacement therapy and positive pressure-assisted ventilation support were ineffective. DIAGNOSIS: The infant was clinically diagnosed with RDS. Genetic tests revealed a heterozygous missense mutation in the c.168 surfactant protein C (SFTPC) gene. INTERVENTIONS: Tracheal intubation was performed with invasive ventilator-assisted breathing, pulmonary surfactant was administered. Supportive treatment for liver protection and administration of a cardiotonic diuretic, vasodilator, human immunoglobulin (intravenous infusion), fresh frozen plasma, and suspended red blood cells were performed. OUTCOMES: The infant showed poor responses to respiratory and circulatory support, antibiotic treatment, and other treatment methods. The patient was discharged from hospital against the advice of us, cut off from us. The long-term prognosis of the patient after discharge remains unknown. LESSONS: SFTPC gene mutations may be an important risk factor for the development of common lung diseases. Because of the important roles of surfactant functions and metabolism, mutations in these genes can affect the production and function of pulmonary surfactant, leading to severe lung disease in term newborns.

Comparison of acute pneumonia caused by SARS-COV-2 and other respiratory viruses in children: a retrospective multi-center cohort study during COVID-19 outbreak.

BACKGROUND: Until January 18, 2021, coronavirus disease-2019 (COVID-19) has infected more than 93 million individuals and has caused a certain degree of panic. Viral pneumonia caused by common viruses such as respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses have been more common in children. However, the incidence of COVID-19 in children was significantly lower than that in adults. The purpose of this study was to describe the clinical manifestations, treatment and outcomes of COVID-19 in children compared with those of other sources of viral pneumonia diagnosed during the COVID-19 outbreak. METHODS: Children with COVID-19 and viral pneumonia admitted to 20 hospitals were enrolled in this retrospective multi-center cohort study. A total of 64 children with COVID-19 were defined as the COVID-19 cohort, of which 40 children who developed pneumonia were defined as the COVID-19 pneumonia cohort. Another 284 children with pneumonia caused by other viruses were defined as the viral pneumonia cohort. The epidemiologic, clinical, and laboratory findings were compared by Kolmogorov-Smirnov test, t-test, Mann-Whitney U test and Contingency table method. Drug usage, immunotherapy, blood transfusion, and need for oxygen support were collected as the treatment indexes. Mortality, intensive care needs and symptomatic duration were collected as the outcome indicators. RESULTS: Compared with the viral pneumonia cohort, children in the COVID-19 cohort were mostly exposed to family members confirmed to have COVID-19 (53/64 vs. 23/284), were of older median age (6.3 vs. 3.2 years), and had a higher proportion of ground-glass opacity (GGO) on computed tomography (18/40 vs. 0/38, P < 0.001). Children in the COVID-19 pneumonia cohort had a lower proportion of severe cases (1/40 vs. 38/284, P = 0.048), and lower cases with high fever (3/40 vs. 167/284, P < 0.001), requiring intensive care (1/40 vs. 32/284, P < 0.047) and with shorter symptomatic duration (median 5 vs. 8 d, P < 0.001). The proportion of cases with evaluated inflammatory indicators, biochemical indicators related to organ or tissue damage, D-dimer and secondary bacterial infection were lower in the COVID-19 pneumonia cohort than those in the viral pneumonia cohort (P < 0.05). No statistical differences were found in the duration of positive PCR results from pharyngeal swabs in 25 children with COVID-19 who received antiviral drugs (lopinavir-ritonavir, ribavirin, and arbidol) as compared with duration in 39 children without antiviral therapy [median 10 vs. 9 d, P = 0.885]. CONCLUSION: The symptoms and severity of COVID-19 pneumonia in children were no more severe than those in children with other viral pneumonia. Lopinavir-ritonavir, ribavirin and arbidol do not shorten the duration of positive PCR results from pharyngeal swabs in children with COVID-19. During the COVID-19 outbreak, attention also must be given to children with infection by other pathogens infection.

[Expert consensus on the prevention and treatment of drowning in children].

Drowning is a leading cause of accidental injury in children and has a great impact on family and society. The prevention and treatment of drowning is of great importance for reducing mortality rate. This consensus reviews the literature on the epidemiology, rescue, resuscitation, and acute clinical management and prevention of drowning. The panel determines the score of available evidence according to the criteria of Oxford Centre for Evidence-Based Medicine and then makes recommendations on evidence based on such criteria, so as to provide a basis for further reducing the mortality and disability rates caused by drowning.

[Effects of adipose-derived stem cells and non-methylated CpG-oligodeoxynucleotides on peripheral blood CD4+CD25+ regulatory T cells in young mice with food allergy].

OBJECTIVE: To investigate the effects of adipose-derived stem cells (ADSC) and non-methylated CpG-oligodeoxynucleotides (CpG-ODN) on the expression of peripheral blood CD4+CD25+ regulatory T (Treg) cells in young mice with food allergy, as well as their immune intervention effects. METHODS: A total of 40 female BALB/c mice were randomly divided into control group, allergic group, ADSC treatment group, and CpG-ODN treatment group, with 10 mice in each group. A mouse model of food allergy was established by intraperitoneal injection and intragastric administration of ovalbumin (OVA) for sensitization and challenge. The mice in the control group were treated with normal saline at the same dose; the mice in the ADSC treatment group were given intraperitoneal injection of ADSC (1×106 cells for each mouse) before and after OVA challenge, and those in the CpG-ODN treatment group were given intraperitoneal injection of non-methylated CpG-ODN solution (40 µg for each mouse) at 1 hour before challenge by gavage. The allergic symptom scores were determined for each group after model establishment. ELISA was used to measure the serum level of OVA-IgE. Flow cytometry was used to measure the percentage of peripheral blood CD4+CD25+ Treg cells. Hematoxylin and eosin staining was used for the pathological analysis of the jejunum. RESULTS: The allergic group had significantly higher allergic symptom scores and serum level of OVA-IgE than the control group (P<0.05). There were no significant differences in the allergic symptom score and the serum level of OVA-IgE between the ADSC treatment group and the CpG-ODN treatment group (P>0.05), but these two groups had significantly lower allergic symptom scores and serum level of OVA-IgE than the allergic group and significantly higher allergic symptom scores and serum level of OVA-IgE than the control group (P<0.01). The allergic group had a significantly lower percentage of peripheral blood CD4+CD25+ Treg cells than the control group (P<0.05). The ADSC treatment group and the CpG-ODN treatment group had a significantly higher percentage of peripheral blood CD4+CD25+ Treg cells than the allergic group (P<0.05); there were no significant differences between these two groups or between them and the control group (P>0.05). Pathological results showed structural damage and edema in the jejunal villi, a large number of eosinophils, and lymphocyte infiltration in the allergic group, while the ADSC treatment group and the CpG-ODN treatment group had less structural damage and edema in the jejunal villi, a lower number of eosinophils, and less lymphocyte infiltration. CONCLUSIONS: ADSC and non-methylated CpG-ODN have a certain effect in the treatment of food allergy and can increase the percentage of peripheral blood CD4+CD25+ Treg cells and reduce the level of OVA-IgE. They may be associated with the induction of immune tolerance and these two treatment have comparable effects. Detailed mechanisms of action still need further investigation.

Genetic Polymorphisms of SP-A, SP-B, and SP-D and Risk of Respiratory Distress Syndrome in Preterm Neonates.

BACKGROUND We examined selected polymorphisms in 3 pulmonary surfactant-associated proteins (SP) for their influence on serum SP levels and risk of respiratory distress syndrome (RDS) in preterm neonates. MATERIAL AND METHODS Premature infants from a Han population were enrolled, including 100 premature infants with RDS (case group) and 120 premature infants without RDS (control group). SNP genotyping for SP-A (+186A/G and +655C/T), SP-B (-18A/C and 1580C/T), and SP-D (Met11ThrT/C and Ala160ThrG/A) used polymerase chain reaction-restriction fragment length polymorphism. Haplotypes were calculated with Shesis software and serum SP-A/B/D levels were quantified by ELISA. RESULTS Case and control groups exhibited significant differences in genotype and allele frequencies of SP-A (+186A/G, +655C/T) and SP-B (1580C/T). However, no statistically significant differences were observed in the allele and genotype frequencies of SP-B -18A/C, SP-D Met11ThrT/C, and SP-D Ala160ThrG/A. Importantly, serum SP-A and SP-B levels were reduced in RDS patients carrying SP-A (+186A/G, +655C/T) and SP-B (1580C/T) polymorphisms. AA genotype of +186A/G, SP-A level, and CC genotype of 1580C/T were independently correlated with increased RDS risk. CONCLUSIONS SP-A (+186A/G) and SP-B (1580C/T) polymorphisms are strongly associated with the risk of RDS in preterm infants. Notably, reduced serum SP-A levels were correlated with a high risk of RDS and may serve as novel biomarkers for RDS detection and monitoring.

[Immunoregulatory effect of adipose-derived stem cell transplantation in young mouse model of food allergy].

OBJECTIVE: To investigate the immunoregulatory effect of adipose-derived stem cell (ADSC) transplantation by intraperitoneal injection in food-allergic young mice before and after ovalbumin (OVA) sensitization. METHODS: Thirty-two 3-week-old female Balb/c mice were randomly divided into control, allergic model, ADSC treatment, and ADSC prevention groups (n=8 each). A young mouse model of food allergy was established by OVA sensitization via intraperitoneal injection. Each mouse from the prevention and treatment groups was transplanted with 1×10(6) ADSCs on days 1 and 15 post-sensitization, respectively. The allergic symptoms of all groups were observed and scored. The jejunal villi and inflammatory cell infiltration were observed by hematoxylin-eosin staining. Serum levels of allergy-related inflammatory cytokines were measured by Luminex. RESULTS: Compared with the allergic model group, the ADSC prevention and ADSC treatment groups had significantly reduced allergic symptom scores (P<0.05). The two groups also showed significantly alleviated allergic pathological damage of the jejunal mucosa. Serum levels of interleukin (IL)-4, IL-5, IL-6, IL-17A, IL-22 and IL-23 were significantly lower in the ADSC prevention and treatment groups than in the allergic model group (P<0.05). However, the ADSC treatment group had a significantly increased serum interferon-γ level and a significantly reduced serum monocyte chemotactic protein-1 level compared with the allergic model and ADSC prevention groups (P<0.05). CONCLUSIONS: ADSC transplantation, performed before or after sensitization, has an immunoregulatory effect on food allergy in young Balb/c mice, but this effect is better if transplantation is performed after sensitization.

[Effect of non-methylated CpG-ODN on serum TGF-ß and immune regulation in ovalbumin-sensitized young mice].

OBJECTIVE: To explore the effect of non-methylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG-ODN) on serum transforming growth factor (TGF)-ß and immune regulation in ovalbumin (OVA)-sensitized young mice. METHODS: Thirty female BALB/c mice (2-3 weeks old) were randomly divided into control, model, and CpG-ODN intervention groups. A young mouse model of food allergy was established by OVA sensitization. Normal saline of the same volume was used for replacement in the control group. The mice in the intervention group were intraperitoneally injected with CpG-ODN solution 1 hour before every OVA sensitization. Allergic symptoms were observed and scored for each group. The jejunal tissue was histopathologically examined with hematoxylin-eosin staining. Serum OVA-IgE level was measured using ELISA. Serum concentrations of interleukin (IL)-4, interferon (IFN)-γ, and TGF-ß were determined by CBA. RESULTS: Allergic symptoms were observed in the model group and the jejunal tissue showed the pathological characteristics of type I allergic reaction. The allergic symptom scores in the model and CpG-ODN intervention groups were significantly higher than in the control group (P<0.01). The serum levels of OVA-IgE, IL-4, and TGF-ß were significantly higher in the model group than in the control and CpG-ODN intervention groups (P<0.05). The CpG-ODN intervention group had significantly higher serum levels of OVA-IgE, IL-4, and TGF-ß than the control group (P<0.05). Compared with the control and CpG-ODN intervention groups, the model group had a significantly reduced IFN-γ level (P<0.05). CONCLUSIONS: The serum TGF-ß level is increased in the young mouse model of OVA-sensitized food allergy and is involved in the allergy mechanism. Non-methylated CpG-ODN can reduce the serum TGF-ß level in sensitized young mice and play an immunoregulatory role in food allergy.