Objective:To characterize the clinical and genetic features of 2 patients with interleukin-1 receptor associated kinase (IRAK) 4 deficiency and to assess the pathogenicity of their genetic variants.Methods:This case series included two patients diagnosed with IRAK4 gene deficiency at Shenzhen Children′s Hospital and the University of Hong Kong-Shenzhen Hospital between 2019 and 2024. Six healthy children without recent infections or immunodeficiency served as controls. Peripheral blood mononuclear cells were stimulated in vitro with Toll-like receptor 4 (TLR4) agonists, and cytokine levels were quantified using a protein chip assay.Results:The 2 patients, a 5-year-old boy and a 10-year-old girl, presented with recurrent invasive or non-invasive bacterial infections and impaired acute-phase inflammatory responses. Genetic testing identified a homozygous frameshift variant (c.540delT, p.F180Lfs*26) in Patient 1 and compound heterozygous frameshift variants (c.166delT, p.F56fs and c.629delG, p.R210fs) in Patient 2, all predicted to result in truncated IRAK4 proteins. Both patients received regular infection prophylaxis with favorable clinical outcomes. Controls consists of 3 males and 3 females, aged 5-17 years. Following TLR4 stimulation, cytokine levels in Patient 1, Patient 2, and controls (tumor necrosis factor-α 68.6, 103.0, 618.7 (392.7, 824.1); interleukin (IL)-1β 39.8, 10.8, 1 975.5 (1 556.0, 2 096.5); interferon-γ 8.6, 6.2, 13.5 (12.7, 14.9); granulocyte colony-stimulating factor 17.6, 15.9, 2 890.0 (1 622.0, 4 692.8); IL-6 140.1, 352.7, 7 222.5 (5 768.5, 8 043.5); and IL-17 47.5, 44.5, 59.7 (43.4, 69.5), respectively.Conclusions:IRAK4 deficiency should be suspected in patients with early-onset recurrent bacterial infections and attenuated inflammatory response. Homozygous and compound heterozygous frameshift variants in IRAK4 gene lead to truncated IRAK4 proteins and impared innate immune signaling.

Objective:To characterize the clinical and genetic features of 2 patients with interleukin-1 receptor associated kinase (IRAK) 4 deficiency and to assess the pathogenicity of their genetic variants.Methods:This case series included two patients diagnosed with IRAK4 gene deficiency at Shenzhen Children′s Hospital and the University of Hong Kong-Shenzhen Hospital between 2019 and 2024. Six healthy children without recent infections or immunodeficiency served as controls. Peripheral blood mononuclear cells were stimulated in vitro with Toll-like receptor 4 (TLR4) agonists, and cytokine levels were quantified using a protein chip assay.Results:The 2 patients, a 5-year-old boy and a 10-year-old girl, presented with recurrent invasive or non-invasive bacterial infections and impaired acute-phase inflammatory responses. Genetic testing identified a homozygous frameshift variant (c.540delT, p.F180Lfs*26) in Patient 1 and compound heterozygous frameshift variants (c.166delT, p.F56fs and c.629delG, p.R210fs) in Patient 2, all predicted to result in truncated IRAK4 proteins. Both patients received regular infection prophylaxis with favorable clinical outcomes. Controls consists of 3 males and 3 females, aged 5-17 years. Following TLR4 stimulation, cytokine levels in Patient 1, Patient 2, and controls (tumor necrosis factor-α 68.6, 103.0, 618.7 (392.7, 824.1); interleukin (IL)-1β 39.8, 10.8, 1 975.5 (1 556.0, 2 096.5); interferon-γ 8.6, 6.2, 13.5 (12.7, 14.9); granulocyte colony-stimulating factor 17.6, 15.9, 2 890.0 (1 622.0, 4 692.8); IL-6 140.1, 352.7, 7 222.5 (5 768.5, 8 043.5); and IL-17 47.5, 44.5, 59.7 (43.4, 69.5), respectively.Conclusions:IRAK4 deficiency should be suspected in patients with early-onset recurrent bacterial infections and attenuated inflammatory response. Homozygous and compound heterozygous frameshift variants in IRAK4 gene lead to truncated IRAK4 proteins and impared innate immune signaling.

Objective To study the relationship between neurodevelopment and early nutritional status of very low birth weight(VLBW)infants in NICU.Methods VLBW infants admitted to NICU of our hospital from January 2013 to December 2014 and received regular follow-up management at our high-risk infant outpatient clinic were retrospectively studied. All infantsˊdevelopmental quotient ( DQ) were evaluated at 3 months of corrected gestational age ( cGA) . DQ ≥130 was defined as excellent, 115-129 above medium, 85-114 medium, 70 -84 below medium and ≤69 abnormal. According to their DQ scores, infants were assigned into two groups, normal neurodevelopment group ( DQ≥85 ) and abnormal neurodevelopment group ( DQ<85 ) . Nutritional status during hospitalization between the two groups were compared.Results A total of 125 VLBW infants were recruited.At three months of cGA, 2 cases ( 1. 6℅) had excellent DQ score; 3 ( 2. 4℅) above medium; 63 ( 50. 4℅) medium;57 (45. 6℅) below medium. 68 cases (54. 4℅) in the normal development group and 57 (45. 6℅) in the abnormal group. The total energy intake, the proportion of enteral energy supply on 4 d, 7 d, 14 d after birth and amino acid supply on 4 d, 7 d were significantly higher in the normal neurodevelopment group than the abnormal group (P<0. 05). Comparing with the abnormal group, weight loss of VLBW infants in the normal neurodevelopment group was less; the time needed to reach birth weight and exclusive enteral nutrition in the normal neurodevelopment group was shorter. The differences were statistically significant between the two groups(P<0.05).Conclusions VLBW infantsˊearly nutritional status may influence their neurodevelopmental outcome.

Objective To evaluate the efficacy and safety of high-dose ambroxol in treating acute exacerbations in chronic obstructive pulmonary disease (AECOPD).Methods The trial design was random,open,and parallel control.126 patients with AECOPD were involved.High-dose group received ambroxol 150 mg 3 times per day for 7 days (n=46),while conventional-dose group given ambroxol 30 mg 3 times per day for 7 days (n=40) and control group was given a routine treatment (antibiotic therapy,oxygen inhalation and bronchodilators) (n=40).Results The effective rates of high-dose group and conventional-dose group (95.6 ％,77.5 ％) were significantly higher compared with control group (55.0％) (x2 =19.81,4.53,both P＜0.05).The average duration of hospitalization was significantly lower in high-dose group (10.78 ±0.95)d and conventional-dose group (11.75±0.84)d comparing with control group (13.15±0.89)d (q=11.88,7.24,both P＜0.05).The clinical efficacy in high dose group was much better.Conclusions High-dose ambroxol is a safe and efficient therapy in the treatment of acute exacerbations in chronic obstructive pulmonary disease.

AIM: To study the possible molecular mechanism of beta-amyloid peptide_ 1-40 -induced apoptosis in rat cortical neurons. METHODS: 40 mg/L beta-amyloid peptide_ 1-40 (A?_ 1-40 ) was used to induce apoptosis in cultured rat cortical neurons. The level of CDK4, phosphorylated pRB were detected by flow cytometry and immunoblotting; RT-PCR was used to examine the mRNA expression of E2F1 while fluorescent spectrofluorometer was used to measure caspase-3 activity. All of the above study was designed to observe whether the level of CDK4, phosphorylated pRB and E2F1 mRNA expression could be affected by A?_ 1-40 . RESULTS: (1)The level of CDK4, phosphorylated pRB increased markedly 2-4 hours after treatment with A?_ 1-40 , and caspase-3 activity elevated remarkably 12-24 hours after treatment with A?_ 1-40 ; (2) E2F1 mRNA expression was upregulated 3 hours after incubation with A?_ 1-40 . CONCLUSION: A?_ 1-40 may induce apoptosis in rat cortical neurons in a manner dependent on CDK4-pRB-E2F1 pathway.