BackgroundAn increasing number of extremely preterm (EP) infants have survived worldwide. However, few data have been reported from China. This study was designed to investigate the short-term outcomes of EP infants at discharge in Guangdong province.MethodsA total of 2051 EP infants discharged from 26 neonatal intensive care units during 2008–2017 were enrolled. The data from 2008 to 2012 were collected retrospectively, and from 2013 to 2017 were collected prospectively. Their hospitalization records were reviewed.ResultsDuring 2008–2017, the mean gestational age (GA) was 26.68 ± 1.00 weeks and the mean birth weight (BW) was 935 ± 179 g. The overall survival rate at discharge was 52.5%. There were 321 infants (15.7%) died despite active treatment, and 654 infants (31.9%) died after medical care withdrawal. The survival rates increased with advancing GA and BW (p < 0.001). The annual survival rate improved from 36.2% in 2008 to 59.3% in 2017 (p < 0.001). EP infants discharged from hospitals in Guangzhou and Shenzhen cities had a higher survival rate than in others (p < 0.001). The survival rate of EP infants discharged from general hospitals was lower than in specialist hospitals (p < 0.001). The major complications were neonatal respiratory distress syndrome, 88.0% (1804 of 2051), bronchopulmonary dysplasia, 32.3% (374 of 1158), retinopathy of prematurity (any grade), 45.1% (504 of 1117), necrotizing enterocolitis (any stage), 10.1% (160 of 1588), intraventricular hemorrhages (any grade), 37.4% (535 of 1431), and blood culture-positive nosocomial sepsis, 15.7% (250 of 1588). The multivariate logistic regression analysis indicated that improved survival of EP infants was associated with discharged from specialist hospitals, hospitals located in high-level economic development region, increasing gestational age, increasing birth weight, antenatal steroids use and a history of premature rupture of membranes. However, twins or multiple births, Apgar ≤7 at 5 min, cervical incompetence, and decision to withdraw care were associated with decreased survival.ConclusionsOur study revealed the short-term outcomes of EP infants at discharge in China. The overall survival rate was lower than the developed countries, and medical care withdrawal was a serious problem. Nonetheless, improvements in care and outcomes have been made annually.
for the Nasal Oscillation Post-Extubation (NASONE) Study Group IMPORTANCE Several respiratory support techniques are available to minimize the use of invasive mechanical ventilation (IMV) in preterm neonates. It is unknown whether noninvasive high-frequency oscillatory ventilation (NHFOV) is more efficacious than nasal continuous positive airway pressure (NCPAP) or nasal intermittent positive pressure ventilation (NIPPV) in preterm neonates after their first extubation.OBJECTIVE To test the hypothesis that NHFOV is more efficacious than NCPAP or NIPPV in reducing IMV after extubation and until neonatal intensive care unit discharge among preterm neonates. DESIGN, SETTING, AND PARTICIPANTSThis multicenter, pathophysiology-based, assessor-blinded, 3-group, randomized clinical trial was conducted in 69 tertiary referral neonatal intensive care units in China, recruiting participants from December 1, 2017, to May 31, 2021. Preterm neonates who were between the gestational age of 25 weeks plus 0 days and 32 weeks plus 6 days and were ready to be extubated were randomized to receive NCPAP, NIPPV or NHFOV. Data were analyzed on an intention-to-treat basis. INTERVENTIONSThe NCPAP, NIPPV, or NHFOV treatment was initiated after the first extubation and lasted until discharge.MAIN OUTCOMES AND MEASURES Primary outcomes were total duration of IMV, need for reintubation, and ventilator-free days. These outcomes were chosen to describe the effect of noninvasive ventilation strategy on the general need for IMV.RESULTS A total of 1440 neonates (mean [SD] age at birth, 29.4 [1.8] weeks; 860 boys [59.7%]) were included in the trial. Duration of IMV was longer in NIPPV (mean difference, 1.2; 95% CI, 0.01-2.3 days; P = .04) and NCPAP (mean difference, 1.5 days; 95% CI, 0.3-2.7 days; P = .01) compared with NHFOV. Neonates who were treated with NCPAP needed reintubations more often than those who were treated with NIPPV (risk difference: 8.1%; 95% CI, 2.9%-13.3%; P = .003) and NHFOV (risk difference, 12.5%; 95% CI, 7.5%-17.4%; P < .001). There were fewer ventilator-free days in neonates treated with NCPAP than in those treated with NIPPV (median [25th-75th percentile] difference, −3 [−6 to −1] days; P = .01). There were no differences between secondary efficacy or safety outcomes, except for the use of postnatal corticosteroids (lower in NHFOV than in NCPAP group; risk difference, 7.3%; 95% CI, 2.6%-12%; P = .002), weekly weight gain (higher in NHFOV than in NCPAP group; mean difference, −0.9 g/d; 95% CI, −1.8 to 0 g/d; P = .04), and duration of study intervention (shorter in NHFOV than in NIPPV group; median [25th-75th percentile] difference, −1 [−3 to 0] days; P = .01).CONCLUSIONS AND RELEVANCE Results of this trial indicated that NHFOV, if used after extubation and until discharge, slightly reduced the duration of IMV in preterm neonates, and both NHFOV and NIPPV resulted in a lower risk of reintubation than NCPAP. All 3 respiratory support techniques were equally safe for this patient population.
Abstract.Chemoresistance of leukemia constitutes a great challenge for successful treatment of leukemia. Autophagy has recently attracted increasing attention for its role in conferring resistance to various conventional anti-neoplastic regiments. In the present study, the authors showed that WAVE1, a member of WASP family verprolin-homologous proteins, is a critical regulator of chemoresistance during autophagy. It is positively correlated with clinical status in pediatric acute myeloblastic leukemia (AML) and leukemia cell lines. The knockdown of WAVE1 expression decreased autophagy was accompanied by an upregulation of autophagic marker microtubule-associated protein light chain 3 (LC3)-Ⅱ, a degradation of SQSTM1/sequestosome 1 (p62) and the formation of autophagosomes. Moreover, a suppression of WAVE1 expression increased the sensitivity of leukemia cells to chemotherapy and apoptosis, and depletion of WAVE1 expression promoted the translocation of Bcl-2 from mitochondria into the cytoplasm. In addition, a knockdown of PI3K-Ⅲ expression significantly inhibited WAVE1-mediated autophagy. Furthermore, suppression of WAVE1 expression blocked the interactions between Beclin1 and PI3K-Ⅲ and the disassociation of Beclin1-Bcl-2 during enhanced autophagy. The above results suggested that WAVE1 is a critical pro-autophagic protein capable of enhancing cell survival and regulating chemoresistance in leukemia cells potentially through the Beclin1/Bcl-2 and Beclin1/PI3K-Ⅲ complex-dependent pathways.
Background Group B Streptococcus (GBS) is a leading cause of early-onset disease (EOD) and late-onset disease (LOD) in infants. We sought to investigate the antibiotic susceptibility profiles, resistance genes, virulence-related genes, serotype distribution and genotypic characteristics of GBS recovered from infected or colonized neonates and pregnant women in a tertiary teaching hospital in Shenzhen, China, from 2008 to 2015. Results High resistance rates of erythromycin (66.7–100%) were detected among early-onset GBS (EOGBS), late-onset GBS (LOGBS), neonatal colonizing GBS (NCGBS) and maternal colonizing GBS (MCGBS). 89.5–100% of four groups of GBS isolates showed resistance to tetracycline. More than 90 % of erythromycin resistant isolates of EOGBS (8/8, 100%), LOGBS (16/17, 94.1%) and NCGBS (10/11, 90.9%) harbored ermB , while only 9.1–17.6% harbored mefA/E . By contrast, 55.8% (24/43) and 62.8% (27/43) of erythromycin resistant MCGBS isolates carried ermB and mefA/E genes, respectively. The tetO gene was more common in tetracycline resistant EOGBS (10/11, 90.9%), LOGBS (17/17, 100%) and NCGBS (10/11, 90.9%), compared to tetracycline resistant MCGBS (12/51, 23.5%). Additionally, the tetM gene accounted for 90.9% (10/11), 76.5% (13/17), 45.5% (5/11) and 80.4% (41/51) of four groups of isolates, respectively. Serotype III was the most predominant in EOGBS (8/12, 66.7%) and LOGBS (15/17, 88.2%), while serotype Ib accounted for 50.0% (6/12) of NCGBS, and serotype Ia and III accounted for 45.6% (26/57) and 33.3% (19/57) of MCGBS, respectively. Sequence type 17 (ST17) was the most common in EOGBS (6/12, 50%) and LOGBS (12/17, 70.6%), while ST12 was predominant in NCGBS (5/12, 41.7%), and five STs (ST19, ST23, ST12, ST103 and ST485) accounted for 66.7% (38/57) of the MCGBS. All serotype III-ST17 isolates recovered from neonates were associated with invasive infections. Conclusions This study shows the meaningful differences in molecular mechanisms of resistance to erythromycin and tetracycline, and the prevalence of serotypes and STs among GBS recovered from neonates and pregnant women. ST17 is predominant in neonatal invasive GBS, but rare in NCGBS and MCGBS. Electronic supplementary material The online version of this article (10.1186/s12866-019-1551-2) contains supplementary material, which is available to authorized users.
Uremia can affect hepatic metabolism of drugs by regulating the clearance of drugs, but it has not been clarified whether gene silencing could modulate the epithelial–mesenchymal transition (EMT) process in uremia. Hence, we investigated the effect of WISP1 gene silencing on the renal tubular EMT in uremia through the wnt/β‐catenin signaling pathway. Initially, microarray‐based gene expression profiling of uremia was used to identify differentially expressed genes. Following the establishment of uremia rat model, serum creatinine, and urea nitrogen of rats were detected. Renal tubular epithelial cells (TECs) were transfected with shRNA‐WISP1 lentivirus interference vectors and LiCI (the wnt/β‐catenin signaling pathway activator) to explore the regulatory mechanism of WISP1 in uremia in relation to the wnt/β‐catenin signaling pathway. Then, expression of WISP1, wnt2b, E‐cadherin, α‐SMA, c‐myc, Cyclin D1, MMP‐2, and MMP‐9 was determined. Furthermore, TEC migration and invasion were evaluated. Results suggested that WISP1 and the wnt/β‐catenin signaling pathway were associated with uremia. Uremic rats exhibited increased serum creatinine and urea nitrogen levels, upregulated WISPl, and activated wnt/β‐catenin signaling pathway. Subsequently, WISP1 silencing decreased wnt2b, c‐myc, Cyclin D1, α‐SMA, MMP‐2, and MMP‐9 expression but increased E‐cadherin expression, whereas LiCI treatment exhibited the opposite trends. In addition, WISP1 silencing suppressed TEC migration and invasion, whereas LiCI treatment promoted TEC migration and invasion. The findings indicate that WISP1 gene silencing suppresses the activation of the wnt/β‐catenin signaling pathway, thus reducing EMT of renal TECs in uremic rats.
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