Efficacy and safety of different inhaled corticosteroids for bronchopulmonary dysplasia prevention in preterm infants: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of inhaled corticosteroids (budesonide, beclomethasone, or fluticasone propionate) in preventing bronchopulmonary dysplasia (BPD) for premature infants. METHOD: Electronic databases, including PubMed, EMBASE, Web of science, Scopus, and Cochrane library, were searched from databases inception to January 2022 for eligible randomized controlled trials. Clinical outcomes such as BPD, mortality, BPD or death, adverse events, and neurodevelopmental outcomes were assessed. RESULTS: Overall, budesonide was significantly associated with a reduction in BPD at 36 weeks' postmenstrual age (RR 0.48; 95 % CI [0.38, 0.62]) and patent ductus arteriosus (PDA) (RR 0.75; 95 % CI [0.63, 0.89]) compared with control treatments. Early longer duration inhalation of budesonide alone was associated with a lower risk of BPD at 36 weeks' postmenstrual age and PDA compared with controls. Early shorter duration intratracheal instillation of budesonide with surfactant as vehicle was associated with a lower risk of BPD at 36 weeks' postmenstrual age and all-cause mortality compared with surfactant. There was no statistically significant difference between budesonide and control groups regarding neurodevelopmental impairment. Beclomethasone and fluticasone propionate did not show any superior or inferior effect on clinical outcomes compared to control treatments. CONCLUSION: These findings suggest that budesonide, especially intratracheal instillation of budesonide using surfactant as a vehicle, is a safe and effective option in preventing BPD for preterm infants. More well-design large-scale trials with long-term follow-ups are necessary to verify the present findings.

Innate Immune Evasion by Human Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is the leading cause of severe respiratory infection in young children. Nearly all individuals become infected in their early childhood, and reinfections with RSV are common throughout life. Primary infection with RSV is usually involved in the symptom of bronchiolitis and pneumonia in the lower respiratory tract, which accounts for over 3 million hospitalizations and approximately 66,000 deaths annually worldwide. Despite the widespread prevalence and high morbidity and lethality rates of diseases caused by RSV infection, there is currently no licensed RSV vaccine. During RSV infection, innate immunity plays the first line of defense to suppress RSV infection and replication. However, RSV has evolved multiple mechanisms to evade the host's innate immune responses to gain a window of opportunity for efficient viral replication. This review discusses the comprehensive interaction between RSV infection and the host antiviral innate immunity and updates recent findings on how RSV modulates the host innate immune response for survival, which may provide novel insights to find potent drug targets and vaccines against RSV.

The diterpenoid adenanthin upregulates the expression of natural killer group 2D receptor ligands in hepatocellular carcinoma cells.

OBJECTIVE: The natural killer (NK) group 2D (NKG2D) receptor plays a crucial role in NK cell-mediated anti-tumor immunity. NKG2D anti-proliferative effect is mediated by direct interactions of the receptor with its ligands that may be considered as a potential target for NK-based immunotherapeutic strategy in cancer cells. METHODS: Here we report that a natural product adenanthin significantly promotes NKG2D ligands expression in hepatoma cells. The effect was determined using flow cytometry analysis. The activity of NK cell was evaluated by measuring its degranulation activity and cytotoxicity. RESULTS: Our data indicates that the induction of NKG2D ligand binding to liver cancer cell surface receptors greatly improves the killing activity of NK cells against the cancer cells. CONCLUSIONS: This is the first report of a new mechanism anti-cancer effects of adenanthin mediated by an indirect activation of NK cells. Our data suggests that adenanthin may be used to sensitize NK cells in tumor immunotherapy.

A New Method for Screening Natural Products to Stimulate IFN-γ Production in Jurkat Human T Lymphocytes.

Interferon-γ (IFN-γ) is a critical cytokine in the defense against viral and bacterial infection. It is mainly produced by natural killer cells and activated T cells. Given its regulatory role in coordinating cellular and humoral immune responses, IFN-γ is considered to be an effective therapeutic agent in the treatment of viral infection. Here we established a fluorescence-based high-content screening model to find small molecules that can stimulate the production of IFN-γ in human Jurkat cells. After a primary screening of 267 natural products, two hits, Astragalus polyphenols and 6-shogaol, were identified to promote the activity of the IFN-γ promoter and subsequently validated by the flow cytometry assay. Obviously, both Astragalus polyphenols and 6-shogaol exhibited potential to induce the transcription and expression of IFN-γ in a dose-dependent manner. These results indicated that our high-content screening model could be a credible and useful platform to contribute to the discovery of novel molecules to promote the expression of IFN-γ and provide leading compounds for the treatment of viral infectious diseases.

[Effects of 37 centigrade volume resuscitation on coagulation function and blood lactic acid in neonates with septic shock].

OBJECTIVE: To investigate the effect of volume resuscitation with normal saline (NS) at 37 centigrade on the coagulation function and microcirculation of neonates with septic shock. METHODS: Children with septic shock admitted to neonatal intensive care unit (NICU) of the First Affiliated Hospital of Gannan Medical University were enrolled. Twenty-four newborns with septic shock were divided into two groups by random number table method (12 in each group), and were resuscitated with 10 mL/kg at 25 centigrade NS and 37 centigrade NS respectively on the basis of routine treatment. Factor II, V, VII, VIII, IX, X, and prothrombin time (PT), thrombin Time (TT), fibrinogen (FIB), activated partial thromboplastin time (APTT), D-Dimer (DD), lactic acid (Lac) were detected before treatment and 6 hours and 12 hours after treatment. RESULTS: The levels of coagulation factors II, V, VII, VIII, IX, X were not significantly changed before and after treatment in the two groups, and there was no significant difference between the two groups. After treatment, PT and APTT in both groups were gradually shortened, DD and Lac were gradually decreased, FIB were gradually increased, while TT had no significant change. Among them, PT, APTT, DD and Lac at 6 hours after treatment in 37 centigradeNS group were significantly lower than those before treatment [PT (s): 14.07±1.02 vs. 17.08±1.54, APTT (s): 54.83±12.39 vs. 69.17±16.36, DD (mg/L): 2.40±0.63 vs. 4.18±0.88, Lac (mmol/L): 2.84±0.82 vs. 5.98±1.17, all P < 0.05]; DD and Lac at 6 hours after treatment in 25 centigrade NS group were significantly lower than those before treatment [DD (mg/L): 3.13±0.84 vs. 4.16±1.04, Lac (mmol/L): 4.83±0.64 vs. 5.69±0.74, both P < 0.05], and PT at 12 hours after treatment was significantly shorter than that before treatment (s: 14.63±1.14 vs. 16.48±1.61, P < 0.01); FIB in both 25 centigrade NS group and 37 centigrade NS group at 12 hours after treatment were significantly higher than those before treatment (g/L: 2.83±0.83 vs. 1.58±0.43, 2.87±0.87 vs. 1.47±0.41, both P < 0.01), but TT had no significant change. The comparison between groups showed that PT, DD and Lac in the 37 centigrade NS group were significantly lower than those in the 25 centigrade NS group at 6 hours after treatment [PT (s): 14.07±1.02 vs. 15.69±1.21, DD (mg/L): 2.40±0.63 vs. 3.13±0.84, Lac (mmol/L): 2.84±0.82 vs. 4.83±0.64, all P < 0.05]; at 12 hours after treatment, PT, APTT and DD in the 37 centigrade NS group were significantly lower than those in the 25 centigrade NS group [PT (s): 13.26±0.91 vs. 14.63±1.14, APTT (s): 37.08±10.43 vs. 54.75±14.96, DD (mg/L): 1.20±0.59 vs. 2.06±0.69, all P < 0.01], and FIB was significantly higher than that in the 25 centigrade NS group (g/L: 2.87±0.87 vs. 2.83±0.83, P < 0.05). CONCLUSIONS: Volume resuscitation at 37 centigrade can improve the coagulation function and microcirculation of newborns with septic shock.