Objective To investigate the neuroprotective effects and mechanisms of 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/ IMP cyclohydrolase(AICAR) supplement (AMPK activator) in different stages of neonatal rats sufferring from hypoxia-ischemia encephalopathy ( HIE). Methods Neonatal rat hypoxia-ischemia brain injury model was employed in this study. A total of 160 neonatal rats were distributed into five groups: sham, model control,AICAR30 min, AICAR24 h and AICAR72 h. The neuroprotective effects of AICAR supplement (30 min, 24 h, 72 h post operation) were compared by cresyl violet staining; Expressions of P-AMPK,AMPK in the brain tissue were measured by Western blotting.Foot-faults method was used to evaluate the long-term prognosis of the rats. Results Compared with the sham group, the survival of rats brain in model control group was significantly decreased [(100.0± 0.1)% and (45.3± 6.3)%, P< 0.05]. AICAR had neuroprotective effects when treated at 30 min and 24 h post operation,while the protective effects disappeared when treated later (72 h post operation) (P>0.05). Compared with the sham group, the expression of P-AMPK significantly increased about three times, while ATP level decreased close to the same. Conclusion Early AICAR treatment can protect hypoxia-ischemia brain injury by increasing AMPK-ATP level.

Objective To investigate the efficacy and safety of aminophylline,caffeine citrate and aminophylline combined with naloxone in prevention of apnea of prematurity(AOP).Methods Ninety-four infants with a birth weight ＜ 1 500 g and gestational age ＜ 34 weeks admitted to Department of Pediatrics,Tongji Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology between Jan.2010 and Jan.2012 were randomly divided into 3 groups.(1) Aminophylline group (n =30):30 infants received a loading dose of 4-5 mg/kg of aminophylline and then maintained by a dose of 2 mg/kg,with intravenous drip q12 h.(2) Caffeine citrate group(n =32):a loading dose of 20 mg/kg of caffeine citrate was followed by a daily maintained dose of 5 mg/kg,with intravenous drip per day.(3) Aminophylline combined naloxone group (observation group,n =32):32 infants were treated with Aminophylline combined with naloxone.After 6 hours of the first dose of aminophylline,a dose of 0.1 mg/kg naloxone was injected,q12 h.Then the two drugs were used alternately.The mortality and incidence of AOP,bronchopulmonary dysplasia(BPD),retinopathy of prematurity (ROP) and brain injury were evaluated,and drug-related side effects were recorded.Results 1.There was no significant difference in gender,gestational age,birth weight,maternal antenatal glucocorticoid application,pregnancy (including multiple pregnancy) and delivery,5 min Apgar score,oxygen therapy,and the application of positive airway pressure as well as pulmonary surfactant among the 3 groups(all P ＞0.05).2.Compared with aminophylline group,the incidence of apnea of caffeine group and observation group were significantly lower (F =6.704,P ＜ 0.05),but there was no significant difference between caffeine group and observation group (P ＞0.05).3.There was no statistically significant difference in mortality,duration of oxygen therapy,the incidence of ROP,brain injury and hearing loss,postmenstrual age,body weight at discharge,the duration and cost of hospitalization among the 3 groups(all P ＞0.05).4.The BPD incidence in caffeine group[9.4％ (3/32 cases)] and observation group [12.5％ (4/32 cases)] were lower than that in Aminophylline group [20.0％ (6/30 cases)],but there was no statistical significance among the 3 groups(P ＞ 0.05).5.No drug-related side effects were recorded in the 3 groups.Conclusions It is safe and effective to use aminophylline combined with naloxone in prevention of AOP,and its efficiency is similar to caffeine citrate.

Objective To investigate the diagnosis,treatment and prognosis of neonates with severe acute respiratory distress syndrome (ARDS) according to Berlin definition.Methods A retrospective study was carried to analyze the clinical features about diagnosis,treatment,chest X-ray findings,mortality,complications and ventilator parameters in 86 neonates with severe ARDS admitted in the NICU from January 2005 to December 2013.Results (1)Among the 86 cases,55 were cured,and 31 died with 36.0％ mortality.(2) Chest X-ray showed there was decreased lucency of bilateral lungs with ground-glass appearance,lung texture with thick chaos or dot flakes or patchy shadows in 36 neonates; diffuse infiltrates and extensive confluent consolidation shadows in bilateral lungs along with peripheral air brornchograms in 26 cases; heart shadow and diaphragmatic surface disappeared like a white lung change in 24 cases.(3) Persistent pulmonary hypertension of newborn as a complication occurred in 68 cases with 79.1％ incidence.(4) Eighty-six cases were categorized into survival group and death group.The results showed compared with the survival group,the neonates in death group required higher FiO2,and PaO2,and lower PaO2/FiO2 before mechanical ventilation (P ＜ 0.01),but needed higher initial PIP of mechanical ventilation (P ＜ 0.01).Conclusions Neonatal ARDS is still a kind of critical condition with high mortality and lack of evidence-based diagnostic criteria so far.The therapeutic strategy for neonatal ARDS should be a comprehensive measures in addition to appropriate respiratory support.

Objective To summarize the cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation spectrum in Chinese children with cystic fibrosis(CF).Methods The data of Chinese children with CF reported in China national knowledge infrastructure,wanfang database,VIP journal database,PubMed were collected.The CFTR gene mutations of the patients retrieved and summarized,1 case diagnosed in the First Affiliated Hospital,Guangzhou Medical University were summarized.Inclusion criteria included:data from published literature,the cases reported were Chinese children with CF and with CFTR gene mutations.Exclusive criteria included:repetitive reports,undiagnosed patients,or patients without CFTR gene mutations.Results There were 58 Chinese children with CF,and 61 CFTR gene mutations were found.The CFTR gene mutations were ranked in order from more to less as the following:c.2909G→A (p.G970D) (9 times);1898 ±5G→T,which was not found in Caucasians,and c.263T→G(6 times respectively);c.3196 C--→T,c.1766 ± 5 G→T,c.3068 T→ G (5 times respectively);2215 insG,c.1666A→ G (4 times respectively);G2816A,c.293A→G,c.595C→T,c.326A→G (3 times respectively);c.3635delT,c.2907A→C,c.648 G→A (W216X),c.960_961insA (1092insA),c.1075C→T,c.1699G→T,c.2491-126T→C,c.3307delA and c.110 C→G were novel observation.△F508 was not found.Conclusions The most common CFTR gene mutation is c.2909G→A (p.G970D) in Chinese children with CF.△ F508 which is the most common mutation in Caucasian not found in Chinese children with CF.The gene mutation spectrum of CFTR in Chinese children with CF is significantly different from those in European and American countries.

The recent investigations have demonstrated that epigenetic such as DNA methylation and histone modification was closely associated with cell growth and malignant tumors, and epigenetic modification was responsible for an important cause of oncogenesis. However, for the recent years some observations have been also shown that the development of tumorigenesis was attributed to transformation expression in microRNA. The latest investigations have revealed that epigenetic was involved in modulation of microRNA expression, on the contrary some kinds of microRNAs could also control epigenetic, moreover, the reciprocal modulation between microRNA and epigenetic could regulate gene expression and induce tumorigenesis. At the same time the data likewise displayed that epigenetic adjusted microRNA expression principally in a way of DNA methylation or histone modification, nevertheless microRNA regulated epigenetic by way of methyltransferases expression, DNA methylation maintenance and histone modification. With regard to the reciprocal modulation between microRNA and epigenetic, a comprehensive and systemic review of reciprocal relationship in modulation of cell growth and oncogenesis was gived.

Objective To determine the dynamic changes in adenosine monophosphate-activated protein kinase (AMPK) in neurons of neonatal rats suffering from hypoxic ischemic brain injury.Methods Twenty-four-hour old and seven-day old neonatal rats were used in this study.A classic primary cortical neuron oxygen glucose deprivation (OGD) model and neonatal rat hypoxic ischemic encephalopathy (HIE) model were employed.Lactic dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) were used to evaluate neuron viability and damage.The expression of phosphorylated adenosine monophosphate-activated protein kinase (P-AMPK),phosphorylated activated protein kinase (P-Akt) and Cleaved Caspase-3 in neurons and brain tissue was measured by Western blot at different time points after OGD or HIE.The Student-t test was used for statistical analysis.Results (1) Compared with the control group,LDH levels at 2,4,8 and 24 h after OGD were higher (all P＜0.05) and optical absorption levels of MTT were lower (all P＜0.05).(2) Levels of P-AMPK in the OGD group were higher than those in the control group,and showed a time-dependent increase at 30 min and 2,4,8 and 24 h (all P＜0.05).The expression levels of P-AMPK in the HIE group were higher than those in the control group (0.345 ± 0.038,0.387 ± 0.112 and 0.618 ± 0.075 at 1,3 and 7 days after HIE,and 0.132±0.032 in the control group,all P＜0.05).(3) The levels of P-Akt increased above the control levels at 30 min (0.991 ±0.134 vs 0.304±0.050),reached a maximum level at 2 h (1.183± 0.107),and then gradually declined,whereas the levels of Cleaved Caspase-3 started to increase at 30 min,and remained elevated at 24 h (all P＜0.05).Conclusion Following hypoxic ischemic brain damage,the expression of P-AMPK is significantly increased in both in vivo and in vitro studies in a time-dependent manner.

OBJECTIVEThe aim of the present study was to prepare uniform-sized silybin loaded poly (lactic-co-glycolic acid) (PLGA) microspheres in study of silybin with stainless steel membrane.

METHODSilybin PLGA microspheres were prepared by stainless steel membrane emulsification. The preparation conditions were optimized by single-factor test and orthogonal experiment, and evaluating the mean diameters, the particle size distribution, drug loading, entrapment efficiency and morphology of microsphere.

RESULTPrepared microspheres were round and surface was smooth. The mean diameter was (4.961 +/- 0.56) microm. The span was (1.75 +/- 0.18). The entrapment efficiency was (54.997 +/- 4.05)% and the average drug loading was (23.6 +/- 1.70)%.

CONCLUSIONThe stainless steel membrane emulsification can be used to prepare the silybin PLGA microspheres. The mean diameters of the silybin PLGA microspheres can be controlled in certain level. Stainless steel membrane emulsification has great potentiality exploitation and utilization.

Drug Compounding ; methods ; Emulsions ; chemistry ; Lactic Acid ; chemistry ; Microspheres ; Particle Size ; Polyglycolic Acid ; chemistry ; Silymarin ; chemistry ; Stainless Steel ; chemistry

Sphingosine kinase 1 (SphK1) plays critical roles in cell biological functions. Here we investigated the effects of SphK1 inhibitor SKI II on hepatoma HepG2 cell cycle progression and invasion. Cell survival was determined by SRB assay, cell cycle progression was assayed by flow cytometry, the ability of cell invasion was measured by Matrigel-Transwell assay and protein expression was detected by Western blotting. The results showed that SKI II markedly inhibited HepG2 cell survival in a dose-dependent manner, induced G1 phase arrest in HepG2 cell and inhibited cell invasion. SKI II markedly decreased the expressions of G1-phase-related proteins CDK2, CDK4 and Cdc2 and the levels of cell invasion-associated proteins MMP2 and MMP9. The results showed that SKI II inhibited cell cycle progression and cell invasion, implying SphK1 as a potential target for hepatoma treatment.
CDC2 Protein Kinase ; Cell Movement ; drug effects ; Cell Survival ; drug effects ; Cyclin-Dependent Kinase 2 ; metabolism ; Cyclin-Dependent Kinase 4 ; metabolism ; Cyclin-Dependent Kinases ; metabolism ; G1 Phase ; drug effects ; Hep G2 Cells ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Phosphotransferases (Alcohol Group Acceptor) ; antagonists & inhibitors ; Thiazoles ; pharmacology

Objective To summarize the CT and MRI features of radiation-induced sarcoma (RIS) after radiotherapy in patients with nasopharyngeal carcinoma (NPC).Methods From January 1997 to October 2012,a total of 73 NPC patients with RIS after radiotherapy were confirmed by pathology.The clinical data and imaging findings (CT and MRI findings) were retrospectively reviewed.Of the 73 patients,43 underwent CT examination,24 underwent MRI,and the remaining 6 underwent both CT and MRI scans.Results Fibrosarcoma [45.3％ (33/73)] was the most frequently histologic type,followed by osteosarcoma[31.5％ (23/73)] and malignant fibrous histiocytoma [9.6％ (7/73)].The top three common sites were maxillary sinus [26.7％ (20/73)],followed by the neck soft tissue [17.8％ (13/73)] and mandible[13.7％ (10/73)].The main characteristics of the RIS on CT and MRI were soft tissue masses[78.1％ (57/73)] with an irregular shape and ill-defined margin,or rounded masses with welldefined margin [21.9％ (16/73)].CT of 49 patients showed masses with isodensity or mixed density on precontrast CT.MRI of 30 patients showed lesions with isointensity signal on T1WI and intermediate signal intensity on T2WI.On post-contrast images,65.8％ (48/73) tumors showed markedly homogeneous or inhomogeneous enhancement,23.2％ (17/73) lesions showed moderate enhancement,and 11.0％ (8/73) masses showed mild enhancement.Among the 23 patients with radiation-induced osteosarcomas,78.3％ (18/23) presented tumor bone formation.Conclusions RIS has a characteristic imaging features.Clinical history,tumor sites and serial imaging follow-up are necessary for early detection of RIS in patients with NPC.

Objective To study the diagnosis and treatment of hepatocellular adenoma(HCA).Methods The preoperative imaging findings,pathologic specimens and surgical treatment of 18 patients with HCA who were admitted in our hospital from January 1990 to April 2007 were retrospectively analyzed.Results Most patients were male(male-to-female:11/7)and only 1 female patient had oral contraceptive history.Six patients presented with pain in the right upper quadrant.Contrast-enhanced CT and contrast-enhanced MRI both displayed that most lesions were characterized by homogeneous enhancement on arterial phase,except the lesions affected by irregular hemorrhage or fatty degeneration,and by washout on portal venous phase and delayed phase.All patients received resection.Hemorrhage in the lession was found in 10 patients and precancerous lesion in 2after operation.All patients were alive and well with no recurrence till December 2007.Conclusion The enhanced CT or MRI scanning for HCA has special features.Complete resection is the first choice for HCA.