Honokiol induces apoptosis and autophagy in dexamethasone-resistant T-acute lymphoblastic leukemia CEM-C1 cells.

Objective: To study whether and, if so, how honokiol overcome dexamethasone resistance in DEX-resistant CEM-C1 cells. Methods: We investigated the effect of honokiol (0-20 µM) on cell proliferation, cell cycle, cell apoptosis and autophagy in DEX-resistant CEM-C1 cells and DEX-sensitive CEM-C7 cells. We also determined the role of c-Myc protein and mRNA in the occurrence of T-ALL associated dexamethasone resistance western blot and reverse transcription-qPCR (RT-qPCR) analysis. Results: Cell Counting Kit (CCK)-8 assay shows that DEX-resistant CEM-C1 cell lines were highly resistant to dexamethasone with IC50 of 364.1 ± 29.5 µM for 48 h treatment. However, upon treatment with dexamethasone in combination with 1.5 µM of honokiol for 48 h, the IC50 of CEM-C1 cells significantly decreased to 126.2 ± 12.3 µM, and the reversal fold was 2.88. Conversely, the IC50 of CEM-C7 cells was not changed combination of dexamethasone and honokiol as compared to that of CEM-C7 cells treated with dexamethasone alone. It has been shown that honokiol induced T-ALL cell growth inhibition by apoptosis and autophagy via downregulating cell cycle-regulated proteins (Cyclin E, CDK4, and Cyclin D1) and anti-apoptotic proteins BCL-2 and upregulating pro-apoptotic proteins Bax and led to PARP cleavage. Honokiol may overcome dexamethasone resistance in DEX-resistant CEM-C1 cell lines via the suppression of c-Myc mRNA expression. Conclusion: The combination of honokiol and DEX were better than DEX alone in DEX-resistant CEM-C1 cell lines. Honokiol may regulate T-ALL-related dexamethasone resistance by affecting c-Myc.

[Risk factors for neonatal asphyxia and establishment of a nomogram model for predicting neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture: a multicenter study]. / æ¹–åŒ—æ©æ–½åœŸå®¶æ—è‹—æ—è‡ªæ²»å·žæ–°ç”Ÿå„¿çª’æ¯å±é™©å› ç´ åˆ†æžåŠåˆ—çº¿å›¾é¢„æµ‹æ¨¡åž‹çš„æž„å»ºï¼šä¸€é¡¹å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS: The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.

A systematic review and meta-analysis of pulmonary surfactant combined with budesonide in the treatment of neonatal respiratory distress syndrome.

Background: Neonatal respiratory distress syndrome (NRDS), if caused by a lack of pulmonary surfactant (PS), leads to progressive alveolar collapse. Glucocorticoids have anti-inflammatory and anti-allergic effects and can reduce bronchial and pulmonary edema. This research hopes to systematically evaluate the efficacy and safety of animal-derived PS combined with the glucocorticoid drug budesonide in the treatment of NRDS. Methods: Electronic databases (i.e., Wanfang, Weipu, CNKI, PubMed, Embase, Cochrane Library) were searched from inception until May 30th, 2021. Studies relevant to the treatment of pulmonary surfactant combined with budesonide in the treatment of neonatal respiratory distress syndrome were identified. Consequently, all the studies that met the inclusion criteria were considered qualified for screening. For the meta-analysis, all data were analyzed using RevMan 5.3 software. Furthermore, subgroup analysis was performed to evaluate the administration method of budesonide (nebulized inhalation, intratracheal instillation) combined with intratracheal instillation of pulmonary surfactant. Results: A total of 10 articles were included in this study, involving 527 children. This meta-analysis suggests that the treatment of intratracheal infusion of pulmonary surfactant combined with budesonide therapy can effectively (I) reduce the time of mechanical ventilation (OR =-1.72,95% CI: -2.44 to -1.01, P<0.00001); (II) reduce the length of stay (OR =-5.17, 95% CI: -9.35 to -0.99, P=0.02); (III) reduce the incidence of bronchopulmonary dysplasia (BPD) (OR =0.52, 95% CI: 0.39-0.68, P<0.00001); and (IV) reduce the incidence of BPD (RR =0.73, 95% CI: 0.40-1.35, P=0.32). There was no significant difference in the incidence of retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), patent ductus arteriosus (PDA), or sepsis between the experimental group and the control group. Discussion: The treatment of animal-derived pulmonary surfactant combined with budesonide can effectively shorten the hospital stay and reduce the time of invasive mechanical ventilation and the incidence of BPD. Meanwhile, it does not increase the risk of related complications or death. This approach can be applied clinically.

[Effect of low-dose dopamine adjuvant therapy on inflammatory factors and prognosis in preterm infants with necrotizing enterocolitis].

OBJECTIVE: To study the effect of low-dose dopamine adjuvant therapy on inflammatory factors and prognosis in preterm infants with necrotizing enterocolitis (NEC). METHODS: A total of 100 preterm infants with NEC from June 2017 to June 2019 were enrolled and divided into a dopamine treatment group and a conventional treatment group using a random number table, with 50 infants in each group. The infants in the conventional treatment group were given symptomatic treatment, and those in the dopamine treatment group were given low-dose dopamine adjuvant therapy in addition to the conventional treatment. ELISA was used to measure the levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8). The two groups were compared in terms of time to relief of clinical symptoms, fasting time, treatment outcome, prognosis, and adverse reactions. RESULTS: Both groups had significant reductions in the levels of CRP, TNF-α, and IL-8 after treatment, and the dopamine treatment group had significantly lower levels of these markers than the conventional treatment group after treatment (P<0.05). Compared with the conventional treatment group, the dopamine treatment group had significantly shorter time to defecation improvement, time to relief of abdominal distension and diarrhea, and fasting time (P<0.05), a significantly higher response rate (P<0.05), and a significantly lower surgery rate (P<0.05). There were no significant differences in the mortality rate and incidence of adverse events between the two groups (P>0.05). CONCLUSIONS: Low-dose dopamine adjuvant therapy can effectively improve the levels of inflammatory factors and clinical symptoms in preterm infants with NEC and has good safety, and therefore, it holds promise for clinical application.