Molecular Mechanism of Qinghuangsan Against Acute Myeloid Leukemia Based on Network Pharmacology and In Vitro Experiments / 中国实验方剂学杂志

ObjectiveTo predict the therapeutic target genes and related signaling pathways of Qinghuangsan （QHP） in the treatment of acute myeloid leukemia （AML） by network pharmacology，molecular docking，and further clarify its mechanisms through in vitro cell experiment. MethodThe active components and targets of QHP were retrieved from traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP），traditional Chinese medicine integrated database （TCMID），TargetNet and SwissTargetPrediction databases，and AML-related target genes were obtained by GeneCards and online mendelian inheritance in man （OMIM） databases. After screening the common targets of QHP and AML，the protein-protein interaction （PPI） network of the common targets was constructed with STRING，followed by gene ontology （GO） term and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analysis based on RStudio software and clusterProfiler，Bioconductor packages. At the same time，Cytoscape software is used to construct the network of "disease-component-target" and "compound-target-pathway". Select the active ingredients of QHP for molecular docking with the top 8 targets in the "compound-target-pathway" network. In vitro cell experiment and Western blot were used to further verify the anti-AML effect of QHP. ResultThe prediction results show that there are 11 main active components of QHP，and 22 common targets of QHP and AML are collected. KEGG pathway analysis results show that phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） and mitogen-activated protein kinase （MAPK） signaling pathways may play a key role in the treatment of AML disease by QHP. "Compound-target-pathway" network analysis showed that the top 8 targets include Akt1，phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit alpha （PIK3CA），mitogen-activated protein kinase kinase 1 （MAP2K1），TP53，serine/threonine kinase （RAF1），B cell lymphoma（Bcl）-2，cysteine aspartic acid specific protease（Caspase）-9 and JUN. Molecular docking results showed that 3-indolyl-β-D-glucopyranoside was optimally docked with MAP2K1，isovitexin docked with PIK3CA，and indirubin docked with Bcl-2. Cell experiments show that 3-indolyl-β-D-glucopyranoside，isovitexin and indirubin can effectively inhibit the proliferation of AML cells，regulate the MAPK/PI3K signaling pathway，and inhibit the expression of Bcl-2 protein. ConclusionQHP can treat AML through "multi-component，multi-target，multi-pathway" synergistic treatment，and its mechanism of pharmacology may be related to the regulation of MAPK signaling pathway and PI3K/Akt signaling pathway.

Preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and influencing factors for follow-up compliance: a multicenter investigation / 中国当代儿科杂志

OBJECTIVES@#To investigate the preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and the influencing factors for follow-up compliance.@*METHODS@#A multicenter retrospective case-control study was performed for the cases from the multicenter clinical database of 12 units in the Quality Improvement Clinical Research Cooperative Group of Neonatal Severe Hyperbilirubinemia in Jiangsu Province of China from January 2019 to April 2021. According to whether the follow-up of neonatal jaundice was conducted on time after discharge from the department of obstetrics, the neonates were divided into two groups: good follow-up compliance and poor follow-up compliance. The multivariate logistic regression model was used to identify the influencing factors for follow-up compliance of the neonates before admission.@*RESULTS@#A total of 545 neonates with severe hyperbilirubinemia were included in the study, with 156 neonates (28.6%) in the good follow-up compliance group and 389 (71.4%) in the poor follow-up compliance group. The multivariate logistic regression analysis showed that low gestational age at birth, ≥10% reduction in body weight on admission compared with birth weight, history of phototherapy of siblings, history of exchange transfusion of siblings, Rh(-) blood type of the mother, a higher educational level of the mother, the use of WeChat official account by medical staff to remind of follow-up before discharge from the department of obstetrics, and the method of telephone notification to remind of follow-up after discharge were associated with the increase in follow-up compliance (P<0.05).@*CONCLUSIONS@#Poor follow-up compliance is observed for the neonates with severe hyperbilirubinemia after discharge from the department of obstetrics, which suggests that it is necessary to further strengthen the education of jaundice to parents before discharge and improve the awareness of jaundice follow-up. It is recommended to remind parents to follow up on time by phone or WeChat official account.

Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study / 中国当代儿科杂志

OBJECTIVES@#To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment.@*METHODS@#A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group.@*RESULTS@#Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05).@*CONCLUSIONS@#This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.

A multicenter retrospective study on survival rate and complications of very preterm infants / 中国当代儿科杂志

OBJECTIVES@#To study the survival rate and the incidence of complications of very preterm infants and the factors influencing the survival rate and the incidence of complications.@*METHODS@#The medical data of the very preterm infants with a gestational age of <32 weeks and who were admitted to the Department of Neonatology in 11 hospitals of Jiangsu Province in China from January 2018 to December 2019 were retrospectively reviewed. Their survival rate and the incidence of serious complications were analyzed. A multivariate logistic regression analysis was used to evaluate the risk factors for death and serious complications in very preterm infants.@*RESULTS@#A total of 2 339 very preterm infants were enrolled, among whom 2 010 (85.93%) survived and 1 507 (64.43%) survived without serious complications. The groups with a gestational age of 22-25@*CONCLUSIONS@#The survival rate is closely associated with gestational age in very preterm infants. A low 1-minute Apgar score (≤3) may increase the risk of death in very preterm infants, while high gestational age, high birth weight, and prenatal use of glucocorticoids are associated with the reduced risk of death. A low 5-minute Apgar score (≤3) and maternal chorioamnionitis may increase the risk of serious complications in these infants, while high gestational age and high birth weight may reduce the risk of serious complications.

Clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation: a multicenter retrospective analysis / 中国当代儿科杂志

OBJECTIVE@#To evaluate the clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation.@*METHODS@#A retrospective analysis was performed for the preterm infants with a birth weight less than 1 500 g and a gestational age less than 32 weeks who were treated in the neonatal intensive care unit of 20 hospitals in Jiangsu, China from January 2018 to December 2019. According to the intensity of resuscitation in the delivery room, the infants were divided into three groups:non-tracheal intubation (@*RESULTS@#Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly lower rates of cesarean section and use of antenatal corticosteroid (@*CONCLUSIONS@#For preterm infants with a birth weight less than 1 500 g, the higher intensity of resuscitation in the delivery room is related to lower rate of antenatal corticosteroid therapy, lower gestational age, and lower birth weight. The infants undergoing tracheal intubation or ECRP in the delivery room have an increased incidence rate of adverse clinical outcomes. This suggests that it is important to improve the quality of perinatal management and delivery room resuscitation to improve the prognosis of the infants.

Contributing factors for the withdrawal from treatment in neonates with respiratory failure / 中国当代儿科杂志

OBJECTIVE@#To investigate the factors contributing to the withdrawal from treatment in neonates with respiratory failure.@*METHODS@#The medical data of 2 525 neonates with respiratory failure were retrospectively studied, who were reported in 30 hospitals of Jiangsu Province from January to December, 2019. According to whether a complete treatment was given, they were divided into a complete treatment group with 2 162 neonates and a withdrawal group with 363 neonates. A multivariate logistic regression analysis was used to investigate the factors contributing to the withdrawal from treatment in neonates with respiratory failure.@*RESULTS@#The multivariate logistic regression analysis showed that small-for-gestational-age birth, congenital abnormality, gestational age < 28 weeks, living in the rural area or county-level city, and maternal age < 25 years were risk factors for the withdrawal from treatment in neonates with respiratory failure (@*CONCLUSIONS@#Small-for-gestational-age birth, congenital abnormality, gestational age, living area, maternal age, Apgar score at birth, and method of birth are contributing factors for the withdrawal from treatment in neonates with respiratory failure. A poor prognosis and a low quality of life in future might be major immediate causes of withdrawal from treatment in neonates with respiratory failure, which needs to be confirmed by further studies.

Effects of Shenshuaikang Enema Liquid on the Wnt/β-catenin pathway for inhibiting the hypoxia reoxygenation injury in HK-2 cells / 中成药

AIM To investigate the protective effect of serum containing Shenshuaikang Enema Liquid (Rhei Radix et Rhizoma,Salviae miltiorrhizae Radix et Rhizoma,Carthami Flos,Astragali Radix) on HK-2 cells injured by hypoxia/reoxygenation (H/R) and its effect on Wnt/β-catenin pathway.MEHTODS Six New Zealand white rabbits randomly divided into control group,Shenshuaikang high dose group and PBS group (n =2) were treated accordingly for serum collection after 3 days' enema.The HK-2 cells injured by hypoxia/reoxygenation were then administered with serum of rabbits from the control group,PBS group,Shenshuaikang groups (high dose,middle dose and low dose groups due to the differently diluted concentrations) respectively.The H/R damage was determined by ROS fluorescence probe,the cellular damage/apoptosis were analyzed by CFSE/PI method and flow cytometry combined with Annexin V-FITC/PI,and the investigation on effects of drugs on expression of Wnt4 mRNA and β-catenin mRNA were accomplished by fluorescence quantitative PCR.RESULTS The fluorescence intensity of intracellular ROS expression was significantly increased after modeling.CFSE/PI double staining showed that the variant Shenshuaikang dose groups displayed obvious proportional mortality superiority to either the control group or PBS group,and the high dose group achieved the lowest mortality.Annexin V-FITC/PI and flow cytometry showed that,at 12 h,compared with the control group (45.6 ± 2.2)％ and PBS group (41.6 ±0.7) ％,Shenshuaikang groups [low dose group (14.8 ± 0.3) ％,middle dose group (10.3 ± 0.6) ％,high dose group (12.9 ± 0.9)％] obviously inhibited apoptosis/death.Shenshuaikang Enema Liquid medicated serum demonstrated its significant effect on the increase of the Wnt4 mRNA expression and a dual-directional regulation on the expression of β-caterin mRNA by quantitative PCR (P ＜ 0.05).CONCLUSION Inhibition of the apoptosis/death of HK-2 cells with hypoxia/reoxygenation injury due to the serum containing Shenshuaikang Enema Liquid suggests the agent's influence on the activation of Wnt/β-catenin pathway.

Cytobiological characteristic of transplanted autologous free submandibular gland for long-term surviving / 眼科

0.05).Moreover,the growth curves of the two kinds of cells were similar.Con- clusions The cell growth properties of cultured transplanted rabbit SMG are similar to that of normal SMG,the cytobiological charac- teristic of transplanted autologous free rabbit SMG are not changed evidently.