Management and prognosis of extremely preterm infants with gestational age ≤25+6 weeks / 中华儿科杂志

Objective: To investigate the outcomes including major complications and prognosis of extremely preterm infants with gestational age ≤25+6 weeks. Methods: The cross-sectional study enrolled 233 extremely preterm infants with gestational age ≤25+6 weeks who were admitted to the Department of Neonatology of Shenzhen Maternity and Child Healthcare Hospital from January 2015 to December 2021. The clinical data including perinatal factors, treatments, complications, and prognosis were extracted and analyzed. These extremely preterm infants were also grouped according to gestational age and year of admission to further analyze their survival rate, major complications, causes of death, and long-term outcomes. The comparisons between the groups were performed with Chi-square test and Kruskal-Wallis. Results: Among these 233 extremely preterm infants, 134 (57.5%) were males and 99 (42.5%) females. The gestational age was (24.6±0.9) weeks, the birth weight was 710.0 (605.0,784.5) g, and the overall survival rate was 61.8% (144/233). Among the surviving extremely preterm infants, the earliest gestational age was 22+2 weeks and the lowest birth weight was 390 g. There were 17.6% (41/233) of extremely preterm infants had treatment withdrawn and were discharged in line with the will of guardians. Among the rest 192 extremely preterm infants managed with aggressive treatments, 14 (7.3%) died in hospital and 34 (17.7%) had treatment withdrawn later due to severe complications. Of the 192 extremely preterm infants, 144 (75.0%) survived, and the survival rate increased year by year (χ2=26.28, P<0.001) while the mortality decreased year by year (χ2=14.09, P=0.027). Among the survivors, 20.8%(30/144) had no major complications, and the incidence of complications was also negatively related with the gestational age (χ2=7.24, P=0.044), and the length of invasive ventilation was negatively related to the gestational age (χ2=29.14, P<0.001). In the group of less than 23+6 weeks, all extremely preterm infants had one or more major complications. The follow-up were completed in 122 infants and revealed that delayed motor development, language retardation, and hearing and vision impairment accounted for 17.2% (21/122), 8.2% (10/122) and 17.2% (21/122), respectively. Conclusions: Extremely preterm infants with gestational age ≤25+6 weeks are difficult to treat, but the survival rate of infants undergoing aggressive treatments increases year by year. Although the prevalence of major complications is still high, most extremely preterm infants have acceptable prognosis during follow-up.

Fat emulsion tolerance in preterm infants of different gestational ages in the early stage after birth / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the fat emulsion tolerance in preterm infants of different gestational ages in the early stage after birth.</p><p><b>METHODS</b>A total of 98 preterm infants were enrolled and divided into extremely preterm infant group (n=17), early preterm infant group (n=48), and moderate-to-late preterm infant group (n=33). According to the dose of fat emulsion, they were further divided into low- and high-dose subgroups. The umbilical cord blood and dried blood filter papers within 3 days after birth were collected. Tandem mass spectrometry was used to measure the content of short-, medium-, and long-chain acylcarnitines.</p><p><b>RESULTS</b>The extremely preterm infant and early preterm infant groups had a significantly lower content of long-chain acylcarnitines in the umbilical cord blood and dried blood filter papers within 3 days after birth than the moderate-to-late preterm infant group (P<0.05), and the content was positively correlated with gestational age (P<0.01). On the second day after birth, the low-dose fat emulsion subgroup had a significantly higher content of short-, medium-, and long-chain acylcarnitines than the high-dose fat emulsion subgroup among the extremely preterm infants (P<0.05). In the early preterm infant and moderate-to-late preterm infant groups, there were no significant differences in the content of short-, medium-, and long-chain acylcarnitines between the low- and high-dose fat emulsion subgroups within 3 days after birth.</p><p><b>CONCLUSIONS</b>Compared with moderate-to-late preterm infants, extremely preterm infants and early preterm infants have a lower capacity to metabolize long-chain fatty acids within 3 days after birth. Early preterm infants and moderate-to-late preterm infants may tolerate high-dose fat emulsion in the early stage after birth, but extremely preterm infants may have an insufficient capacity to metabolize high-dose fat emulsion.</p>

Effect of the proteasome inhibitor MG-132 on hyperoxic lung injury and its mechanism in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effects of proteasome inhibitor MG-132 on hyperoxic lung injury in rats and explore the mechanism.</p><p><b>METHODS</b>Thirty SD rats were randomly divided into 3 groups, namely the normoxic group, hyperoxic group, and hyperoxic with MG-132 treatment group, and rat models of hyperoxic exposure-induced lung injury were established in the latter two groups. After pathological grading of the lung injury under optical microscope and determination of the wet/dry weight ratio of the lung tissue, the expressions of ubiquitin protein and nuclear factor-kappaB (NF-kappaB) p56 and the activity of proteasome 20S and myeloperoxidase (MPO) were detected. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) expressions in the lung tissue were also detected.</p><p><b>RESULTS</b>The rats with hyperoxic exposure showed obvious pulmonary edema and increased wet/dry weight ratio of the lung tissue (P<0.01), which were significantly alleviated with MG-132 treatment (P<0.01). Compared with the normoxic group, hyperoxic exposure resulted in significant lung pathologies (P<0.01), which was reduced after MG-132 treatment. Immunohistochemistry and Western blotting demonstrated increased expression of ubiquitin protein in the lung tissue after hyperoxic exposure (P<0.01), which was lowered by MG-132 treatment (P<0.01). Proteasome 20S activity was obviously enhanced in the hyperoxic group (P<0.01) but lowered by MG-132 treatment (P<0.01). Hyperoxic exposure also caused obviously enhanced MPO activity and expressions of NF-kappaB, TNF-alpha, and IL-6 (P<0.01), which were all reduced by MG-132 treatment (P<0.05).</p><p><b>CONCLUSION</b>MG-132 alleviates hyperoxic lung injury probably by inhibiting the NF-kappaB/inflammatory factor pathways.</p>

Protective effects of MG-132 on p38 signaling pathway and cell apoptosis in lung injury induced by hyperoxia / 上海第二医科大学学报

Objective To investigate the protective effects of the ubiquitin proteasome inhibitor MG-132 on p38 signaling pathway and apoptosis in lung injury induced by hyperoxia. Methods Twenty-six SD rats were randomly divided into 4 groups: normal control group(n=5),MG-132 control group(n=5),hyperoxia group(n=8) and MG-132 hyperoxia group(n=8).Hyperoxia lung injury rat models were established,and proteasome inhibitor(0.5 mg/kg) was intraperitoneally injected in control group and MG-132 hyperoxia group once daily.The resected lungs were histopathologically examined,and cell apoptosis and expression of ubiquitin and p38 were detected by TUNEL and immunohistochemistry,respectively.Results After hyperoxia exposure,there were edema and inflammatory cell infiltration in the lung tissues of SD rats.The apoptosis index and expression of p38MAPK of hyperoxia group were higher than those of normal control group and MG-132 hyperoxia group(P

Activation of Ubiquitin-Proteasome Pathway in Lung Injury Rat Induced by Hyperoxia in Early Stage / 实用儿科临床杂志

Objective To explore the extent of lung injury induced by hyperoxia,and the activity of ubiquitin-proteasome pathway(UPP) in pathophysiological progress of lung tissue in early stages.Methods Adopted completely random design,20 SD rats were divided into hyperoxia group and air control group.For the air control group,the oxygen concentration exiting the cages was analyzed with oxygen monitor and oxygen concentration remained at 210 mL/L for 72 hours;while in the hyperoxia group,the condition changed into high-density oxygen(950 mL/L) for 72 hours to estimate the hyperoxia lung injury in rats model.The contents linked morphology as pathological classification in gross finding,pathological score of lung injury and the index of pneumonedema-the ratio of moist to dry weight of lungs were mea-sured.The expressions of ubiquitin protein and the activity of proteasome 20 S and the active statement of ubiquitin-proteasome pathway were detected by immunohistochemistry and Western blot methods.Results 1.The hyperoxia lung injury rat model was successfully duplicated.2.In hyperoxia group,pulmonary edema with increased ratio of moist to dry weight of lungs could be found(P=0).3.Macroscopic observation: bright red and full-stacked lung tissue,foliated or local hemorrhage on the surface,but little pleural effusion was observed in hyperoxia group.There was statistical significance of pathological classification in gross finding between hyperoxia group and air control group(P=0.005).Light microscope observation:swelled alveolar epithelium,widened alveoli wall,capillary engorgement and telangiectasis,obvious edema in interstitial tissue of pulmonary aveolus and alveolar space,increased inflammatory cells were observed in hyperoxia group.The findings of pathological score of lung injury indicated more serious injure than control group(P=0).4.The increased expression of ubiquitin protein in lung tissue was discoved by using immunohistochemistry and Western blot findings after hyperoxia exposure 72 hours.(P=0).5.The acti-vity of proteasomes 20 S in hyperoxia group was higher than that in control group(P=0).Conclusions The mainly pathological changes of lung are generated through hyperoxic exposure for 72 hours,including alveolar epithelial cell and vascular endothelial cell injury diffusely,inflammatory cell infiltration and pulmonary edema.Active the ubiquitin-proteasome pathway is connected with the pathophysiological process of lung injury in the initial stages of hyperoxia-exposure.