Anti-cancer Mechanism of Polygonati Rhizoma-Lilii Bulbus Based on Network Pharmacology / 中国实验方剂学杂志

Objective::To screen out active ingredients of Polygonati Rhizoma-Lilii Bulbus, and predict the targets and signaling pathways, in order to explore the potential mechanism in treatment of cancer by using network pharmacology. Method::All of active ingredients and targets of Polygonati Rhizoma-Lilii Bulbus were screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Disease targets for cancer were collected through databases of gene-disease associations (DisGeNET) and Online Mendelian Inheritance in Man (OMIM). Then the Omicshare platform was used to match the active ingredients and the targets for treating cancer. And the " drug-active ingredients-disease targets" network was established using Cytoscape 3.7.0 software. The functional protein association networks (String) database was used to construct the protein interaction network of drug pair targets for treating cancer. Finally, the Functional Annotation Bioinformatics Microarray Analysis (DAVID) database was used to analyze the biological functions and metabolic pathways of key targets. Result::A total of 19 active ingredients were screened out, 234 targets were predicted, 6 active ingredients were identified to be related to cancer. The anti-cancer effect was mainly correlated with the regulation of target proteins in treating cancer, such as Akt serine/threonine kinase 1 (Akt1), Jun proto-oncogene, AP-1 transcription factor subunit (JUN), vascular endothelial growth factor A (VEGFA), matrix metallopeptidase-9 (MMP-9), Caspase-3, Fos proto-oncogene, AP-1 transcription factor subunit (FOS), proteoglycans in cancer, estrogen signaling pathway, human immunodeficiency virus 1 infection, hypoxia inducible factor-1 (HIF-1) signaling pathway, tumor necrosis factor(TNF) signaling pathway, microRNAs in cancer and other pathways. Conclusion::The anti-cancer effect of Polygonati Rhizoma-Lilii Bulbus reflects multi-component, multi-target, multi-pathway characteristics of TCM, and provides a scientific basis for explaining the mechanism and material basis of anti-cancer treatment.

Effect of Histone Deacetylase Inhibition on the Expression of Multidrug Resistance-associated Protein 2 in a Human Placental Trophoblast Cell Line / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Placental multidrug resistance-associated protein 2 (MRP2), encoded by ABCC2 gene in human, plays a significant role in regulating drugs' transplacental transfer rates. Studies on placental MRP2 regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. Currently, the roles of epigenetic mechanisms in regulating placental drug transporters are still unclear. This study aimed to investigate the effect of histone deacetylases (HDACs) inhibition on MRP2 expression in the placental trophoblast cell line and to explore whether HDAC1/2/3 are preliminarily involved in this process.</p><p><b>METHODS</b>The human choriocarcinoma-derived trophoblast cell line (Bewo cells) was treated with the HDAC inhibitors-trichostatin A (TSA) at different concentration gradients of 0.5, 1.0, 3.0, and 5.0 μmol/L. Cells were harvested after 24 and 48 h treatment. Small interfering RNA (siRNA) specific for HDAC1/HDAC2/HDAC3 or control siRNA was transfected into cells. Total HDAC activity was detected by colorimetric assay kits. HDAC1/2/3/ABCC2 messenger RNA (mRNA) and protein expressions were determined by real-time quantitative polymerase chain reaction and Western-blot analysis, respectively. Immunofluorescence for MRP2 protein expression was visualized and assessed using an immunofluorescence microscopy and ImageJ software, respectively.</p><p><b>RESULTS</b>TSA could inhibit total HDAC activity and HDAC1/2/3 expression in company with increase of MRP2 expression in Bewo cells. Reduction of HDAC1 protein level was noted after 24 h of TSA incubation at 1.0, 3.0, and 5.0 μmol/L (vs. vehicle group, all P < 0.001), accompanied with dose-dependent induction of MRP2 expression (P = 0.045 for 1.0 μmol/L, P = 0.001 for 3.0 μmol/L, and P < 0.001 for 5.0 μmol/L), whereas no significant differences in MRP2 expression were noted after HDAC2/3 silencing. Fluorescent micrograph images of MRP2 protein were expressed on the cell membrane. The fluorescent intensities of MRP2 in the control, HDAC2, and HDAC3 siRNA-transfected cells were week, and no significant differences were noticed among these three groups (all P > 0.05). However, MRP2 expression was remarkably elevated in HDAC1 siRNA-transfected cells, which displayed an almost 3.19-fold changes in comparison with the control siRNA-transfected cells (P < 0.001).</p><p><b>CONCLUSIONS</b>HDACs inhibition could up-regulate placental MRP2 expression in vitro, and HDAC1 was probably to be involved in this process.</p>

Role of c-Jun N-terminal kinase-mediated FOXO3a nuclear translocation in neuronal apoptosis in neonatal rats with hypoxic-ischemic brain damage / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the mechanisms of neuroprotective effects of c-Jun N-terminal kinase (JNK)/FOXO3a transcription factor signaling pathway inhibition on hypoxic-ischemic neuronal apoptosis in neonatal rats with hypoxic-ischemic brain damage (HIBD).</p><p><b>METHODS</b>Sixty-four 7-day-old Sprague-Dawley rats were divided into four groups: hypoxia-ischemia (HI), sham-operated, JNK specific inhibitor AS601245-treated, and DMSO vehicle. Rats' cerebral cortexes were collected at 24 hours after HI. Western blot was used to detect the protein expression of JNK, p-JNK, FOXO3a, nuclear and cytoplasmic FOXO3a, Bim, and CC3. TUNEL staining was used to detect the apoptotic cells.</p><p><b>RESULTS</b>Compared with the sham-operated group, p-JNK protein increased (P<0.01), nuclear protein of FOXO3a increased (P<0.01), cytoplasmic protein decreased (P<0.01), and pro-apoptotic proteins Bim and CC3 increased 24 hours after HI (P<0.01). Compared with the HI and DMSO vehicle groups, p-JNK protein was reduced (P<0.01), nuclear protein of FOXO3a was also reduced (P<0.01), cytoplasmic protein increased (P<0.01), and Bim and CC3 proteins decreased (P<0.01) in the AS601245-treated group 24 hours after HI. TUNEL positive cells were reduced in the AS601245-treated rats compared with the HI and DMSO vehicle groups 24 hours after HI (P<0.01).</p><p><b>CONCLUSIONS</b>JNK activity increases in the neonatal rat brain with HI damage. JNK activity inhibition can inhibit FOXO3a translocation from cytoplasm to nucleus and downregulate the levels of pro-apoptotic proteins Bim and CC3, leading to the reduction of neuronal apoptosis.</p>

Clinical efficacy of preferred use of high-frequency oscillatory ventilation in treatment of neonatal pulmonary hemorrhage / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical efficacy and safety of preferred use of high-frequency oscillatory ventilation (HFOV) in the treatment of neonatal pulmonary hemorrhage.</p><p><b>METHODS</b>The clinical efficacy of preferred use of HFOV (preferred use group) and rescue use of HFOV after conventional mechanical ventilation proved ineffective (rescue use group) in the treatment of 26 cases of neonatal pulmonary hemorrhage was retrospectively analyzed. The oxygenation index (OI), pulmonary hemorrhage time, hospitalization time, ventilation time, oxygen therapy time, complications, and outcome of the two groups were compared.</p><p><b>RESULTS</b>Compared with the rescue use group, the preferred use group had significantly lower IO values at 1, 6, 12, 24, 48, and 72 hours after treatment (P<0.05). Compared with the rescue use group, the preferred use group had a significantly lower incidence of ventilator associated pneumonia (VAP) (P<0.05) and a significantly higher cure rate (P<0.05). There were no statistically significant differences in the incidences of pneumothorax, intracranial hemorrhage, and digestive tract hemorrhage between the two groups (P>0.05). Compared with those in the rescue use group, children who survived in the preferred use group had significantly shorter pulmonary hemorrhage time, hospitalization time, ventilation time, and oxygen therapy time (P<0.05).</p><p><b>CONCLUSIONS</b>Compared with the rescue use of HFOV, preferred use of HFOV can better improve oxygenation function, reduce the incidence of VAP, shorten the course of disease, and increase cure rate while not increasing the incidence of adverse effects.</p>

Investigation of pharmacokinetics and pharmacodynamics of different doses of aminophylline in very low birth weight infants / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the pharmacokinetic and pharmacodynamic features of different doses of aminophylline in very low birth weight (VLBW) infants with different postmenstrual ages, weights, and ages (in days).</p><p><b>METHODS</b>A total of 40 VLBW infants with apnea were enrolled. After an intravenous loading dose of 5 mg/kg aminophylline, they were randomized into two groups with different maintenance doses of aminophylline (1 mg/kg and 2 mg/kg, once every 8 hours). Blood concentrations of aminophylline and liver and renal functions were monitored at 8 hours, 3 days, and 7 days after the loading dose. Attacks of apnea were documented. Pharmacokinetic data of aminophylline were compared between the two groups.</p><p><b>RESULTS</b>The steady-state plasma concentration of aminophylline and plasma clearance in the 2 mg/kg group were significantly higher than those in the 1 mg/kg group (P<0.05). However, the elimination half life was shorter in the 2 mg/kg group (P<0.05). Days of apnea attacks within 7 days after birth in the 2 mg/kg group were significantly fewer than in the 1 mg/kg group (P<0.05). Aminophylline plasma clearance was positively correlated with age (in days) after birth and postmenstrual age in both groups.</p><p><b>CONCLUSIONS</b>In VLBW infants, pharmacokinetics and pharmacodynamics are different when different maintenance doses of aminophylline are given. The maintenance dose of 2 mg/kg is associated with a better effect in the treatment of apnea. Postmenstrual age and age (in days) should be considered during the adjustment of dose, and routine blood concentration monitoring should be performed.</p>

A co-word analysis of current research on neonatal jaundice / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the research on neonatal jaundice in recent years by co-word analysis and to summarize the hot spots and trend of research in this field in China.</p><p><b>METHODS</b>The CNKI was searched with "neonate" and "jaundice" as the key words to identify the papers published from January 2009 to July 2013 that were in accordance with strict inclusion and exclusion criteria. To reveal the relationship between different high-frequency key words, Microsoft Office Excel 2013 was used for statistical analysis of key words, and Ucinet 6.0 and Netdraw were used for co-occurrence analysis.</p><p><b>RESULTS</b>A total of 2 054 papers were included, and 44 high-frequency key words were extracted. The current hotspots of research on neonatal jaundice in China were displayed, and the relationship between different high-frequency key words was presented.</p><p><b>CONCLUSIONS</b>There has been in-depth research on clinical manifestations and diagnosis of neonatal jaundice in China, but further research is needed to investigate the etiology, mechanism, and treatment of neonatal jaundice.</p>

Risk factors and complications of severe meconium aspiration syndrome in neonates / 中华实用儿科临床杂志

Objective To provide the clinical evidence for early diagnosis of meconium aspiration syndrome (MAS) and to prevent its complications.Methods One hundred and seven cases of neonates diagnosed with MAS treated in Department of Neonatology,West China Second Hospital,Sichuan University,from Dec.2006 to Dec.2011were analyzed retrospectively.They were assigned into severe MAS group (52 cases) and non-severe MAS group (55 cases) according to whether need mechanical ventilation(including positive end-expiratory pressure and invasive ventilation).Comparisons were carried out with SPSS 15.0,including the general situation of the newborns,obstetric characteristics and complications of both groups.Results There were significant differences in 1 min,5 min and 10 min Apgar score,intrauterine distress,endotracheal intubation meconium suction between the 2 groups.The common complications of MAS were hypoxic-ischemic encephalopathy (HIE) (61.7％),myocardium injury (43.0％),metabolism disorder (41.1％) and intracranial hemorrhage (20.6％).The incidences of HIE,metabolism disorder,disseminated intravascular coagulation,intracranial hemorrhage,pulmonary hemorrhage,myocardium injury and kidney injury in severe MAS group were significantly higher than those in non-severe MAS group.However,no in crease of the prevalence of severe MAS was proved because of clinical conditions,such as maternal pregnancy complications and cesarean section.Conclusions Intrauterine distress and asphyxia are associated with increased the risk of severe MAS.MAS,especially severe one,can lead to multiple organ dysfunction,so it deserves much closer caring and monitoring.

Influence of different antibiotic strategies on outcomes of hospitalized neonates / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To observe the outcomes of hospitalized neonates who were managed with two different antibiotics strategies, namely, the risk factor based antibiotic strategy and the combination antibiotic strategy that is based on risk factors, infection screening and monitoring.</p><p><b>METHODS</b>A cohort study was performed on a control group of 4 406 cases of neonates hospitalized between January 2010 and May 2011 and an observed group of 4 476 neonates hospitalized between July 2011 and October 2012. The control group adopted the risk factor based antibiotic strategy and the observed group received a combination antibiotic strategy based on risk factors, infection screening and monitoring. The rate of antibiotic use, average length of stay, readmission rate and mortality rate were compared between the two groups.</p><p><b>RESULTS</b>With the change from the risk factor based antibiotic strategy to the combination antibiotic strategy, the total rate of antibiotic use decreased from 79.6% to 50.5% (P<0.01). There were no differences in the average length of stay, readmission rate, and mortality rate between the two groups.</p><p><b>CONCLUSIONS</b>The combination antibiotic strategy based on risk factors, infection screening and monitoring can reduce antibiotic use substantially and has no adverse effects on treatment outcomes in hospitalized neonates.</p>

Clinical application of inhaled nitric oxide in hypoxic respiratory failure of preterm infants / 中国当代儿科杂志

Inhaled NO (iNO) has been shown to have beneficial effects on decreasing pulmonary inflammation, increasing function of surfactant and improving lung growth in prematurely born animal models. iNO has been gradually applied in the neonatal intensive care unit since its first use for persistent pulmonary hypertension (PPHN) in the early 1990's. Although many research findings have shown the benefits of iNO for hypoxic respiratory failure (HRF) of preterm infants, there is no certain evidence to support the routine use of iNO in premature infants. According to recent literature, the mechanism of iNO therapy, treatment scheme, iNO effectiveness and safety in premature infants were reviewed in this article, so as to provide bases for the clinical use of this treatment.

Neonatal hypophosphatasia / 中国当代儿科杂志

Hypophosphatasia is a rare inborn disease of metabolism. This paper reviewed its pathogenesis, forms, clinical manifestations, differential diagnosis,treatment and prognosis. Here a case of neonatal hypophosphatasia is reported. This baby was female (30 minutes old). Prenatal ultrasound showed disproportionate biparietal diameter and long bones of limbs in the baby. After birth, she presented with obvious craniomalacia, respiratory distress and cyanosis. Serum alkaline phosphatase level was significantly reduced. Both X-ray and autopsy showed extremely insufficient skeletal mineralization. Four days later she died of respiratory failure.