Research progress in optimizing implantable collamer lens V4c implantation / 国际眼科杂志(Guoji Yanke Zazhi)

With the development of posterior chamber phakic intraocular lenses implantation and the constant improvement of the implantable collamer lens(ICL), ICL V4c implantation has become one of the main methods for correcting moderate and high myopia. Vault is an important indicator to evaluate the security of posterior chamber intraocular lens implantation. In recent years, optimizing surgical procedures to obtain the ideal vault in ICL V4c implantation surgery has become a research hotspot. This paper aims to provide help for improving surgical safety by summarizing and analyzing the optimized programs of ICL V4c implantation surgery. The focus will be on preoperative examination, intraoperative surgical design, and postoperative follow-up.

Clinical characteristics of IgE-mediated cow's milk protein allergy in children / 中华儿科杂志

Objective: To analyze the clinical features of IgE-mediated cow's milk protein allergy (CMPA) in children aged 0-5 years. Methods: This cross-sectional study collected the data on children diagnosed with CMPA in the Department of Allergy at the Children's Hospital of the Capital Institute of Pediatrics from October 2019 to November 2020 and improved peripheral blood routine,total IgE defection, milk specific IgE (sIgE) defection,SPT and milk component defection,diagnosis of severe anaphylaxis based on clinical manifestations. Rank-sum test and chi-square test are used for statistical analysis of clinical characteristics between groups. Results: A total of 106 children (67 boys and 39 girls) were enrolled with the age of 15 (8, 34) months, including 42 cases (≤ 1 year of age), 39 cases (>1-<3 years of age) and 25 cases(≥3 years of age), the onset age of 6 (5, 8) months. Among them, 95 cases (89.6%) were reacted after consuming milk or its products, 42 cases (39.6%) had reaction due to skin contact and 11 cases (10.4%) reacted after exclusive breastfeeding. The onset time of milk product consumption was 45 (1, 120) min, skin contact pathway was 10 (5, 30) min and symptoms in breastfeeding pathway was 121 (61, 180) min. There was statistical difference among the time of symptoms (χ2=77.01, P<0.001).The cutaneous reaction was most common (100 cases, 94.3%), followed by digestive (20 cases, 18.9%) and respiratory (16 cases, 15.1%), and the nervous symptoms (1 case, 0.9%) were uncommon and 24 cases (22.6%) had at least one episode of anaphylaxis. There were 87 cases (82.1%) also diagnosed with other food allergies, 94 cases (88.7%) with previous eczema, 57 cases (53.8%) with history of rhinitis, and 23 cases (21.7%) with history of wheezing. The total IgE level was 191.01 (64.71, 506.80) kU/L, and the cow's milk sIgE level was 3.03 (1.11, 15.24) kU/L. The maximum diameter of the wheal in SPT was 8.2 (4.0, 12.0) mm. Component resolved diagnosis showed that 77 cases (81.9%) were sensitized to at least one out of 4 main components, including casein, α lactalbumin, β lactoglobulin and bovine serum albumin.The possibility of anaphylaxis in children with milk sIgE grade Ⅳ-Ⅵ was higher than that in children with grade 0-Ⅲ (57.7% (15/26) vs. 12.5% (10/80), OR=9.545, 95%CI 3.435-26.523). Children with milk SPT ≥+++ had a higher probability of anaphylaxis than those with milk SPT ≤++ (34.4% (11/32) vs. 11.5% (3/26), OR=4.016, 95%CI 0.983-16.400). Anaphylaxis were more common in α lactalbumin positive children than in negative children (34.3% (13/38) vs. 14.2% (8/56), χ2=1.23，P=0.042). Conclusions: CMPA in children has early onset and diversified clinical manifestations, which are mainly cutaneous symptoms. Most children are sensitized to at least one allergen component. Serum sIgE level, SPT reaction and allergen components play important roles in the diagnosis and evaluation of CMPA, and higher milk sIgE level may predict a higher risk of anaphylaxis.

Influencing factors of the early vault after phakic posterior chamber implantable collamer lens implantation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the early variation trend of the vault after phakic posterior chamber implantable collamer lens/toric implantable collamer lens(ICL/TICL V4c)implantation and analyze the related influencing factors.METHODS:In this retrospective study, a total of 49 patients(98 eyes)who underwent ICL/TICL V4c implantation in the Lanzhou Huaxia Eye Hospital from October 2020 to March 2021 were enrolled. Preoperative ocular biometric parameters were collected, including spherical equivalent(SE), intraocular pressure, axial length, anterior chamber depth(ACD), lens thickness(LT), central corneal thickness, anterior chamber angle(ACA), anterior chamber volume(ACV), white to white corneal diameter(WTW), mean keratometry K1 and K2, and intraoperative implantation size of ICL. The vault was measured by anterior segment optical coherence tomography(AS-OCT)at 1, 3d, 1wk and 1mo after surgery. The patients were divided into insufficient vault group(&#x003C;250μm, 12 eyes), normal vault group(250-750μm, 62 eyes)and excessive vault group(&#x003E;750μm, 24 eyes)according to the vault at 1mo after surgery. The factors affecting the postoperative vault were analyzed.RESULTS:The mean vault values at 1 and 3d, 1wk and 1mo after surgery were 591.05±293.44, 599.62±309.78, 592.22±301.49 and 586.69±285.63μm, respectively. There were significant differences in WTW, ACA, ACV, ACD, ICL size and LT at 1mo after surgery(all P&#x003C;0.05). The regression equation of vault at 1mo after surgery was as follows: vault(μm)=-3142.19+388.25×WTW+10.40×ACA-301.63×LT(R=0.674, R2=0.454, adjusted R2=0.436). WTW had the greatest influence on vault at 1mo after surgery(β=0.47, P&#x003C;0.001), followed by LT(β=-0.34, P&#x003C;0.001)and ACA(β=0.17, P=0.047).CONCLUSION:WTW, ACA and LT were the main factors that affected and predicted the vault at 1mo after ICL/TICL V4c implantation.

Analysis on Urine Metabolomics of Dioscoreae Nipponicae Rhizoma Extract Against Acute Gouty Arthritis / 中国实验方剂学杂志

Objective::To explore the effect of Dioscoreae Nipponicae Rhizoma extract (DNRe) on rats with acute gouty arthritis (AGA) based on urine metabolomics and to search for the related potential biomarkers and metabolic pathways. Method::Rat model of AGA induced by monosodium urate (MSU) was selected, 40 rats were randomly divided into the blank group (k), the DNRe group (g), the model group (m), and the DNRe treatment group (gm), with 10 rats in each group. The drug-administered group was administered with DNRe at a dose of 0.48 g·kg-1 once a day for 5 days. The urine was gathered after the last administration, and analyzed with UPLC-Q-TOF/MS coupled with pattern recognition techniques, electrospray ionization (ESI) under positive and negative ion scanning mode was adopted, data collection range was m/z 100-1 500 with full scanning mode. Result::A total of 12 common potential biomarkers were identified as sarcosine, dimethylglycine, deoxycytidine, uric acid, 5-hydroxytryptamine (5-HT), L-cystathionine, 4-pyridoxic acid, deoxyuridine, melatonin, 5-methoxytryptamine, fumaric acid and cytidine. Compared with the blank group, the 12 potential biomarkers in the DNRe group were significantly down-regulated. Compare with the model group, 10 metabolites were up-regulated and 2 metabolites were down-regulated in the 12 potential biomarkers of the DNRe treatment group, the abnormal expression of 10 markers including sarcosine, uric acid, L-cystathionine, 4-pyridoxic acid, deoxyuridine, 5-methoxytryptamine, cytidine, dimethylglycine, melatonin, fumaric acid could be modulated by DNRe. The strongest metabolic pathways associated with AGA were cysteine and methionine metabolism, and tryptophan metabolism. Conclusion::The effect of DNRe on AGA may be related to the promotion of conversion level from cystathionine to cysteine in the cysteine and methionine metabolism, and the up-regulating melatonin level in tryptophan metabolism.

Discussion on Therapeutic Mechanism of Canhuang Tablets for Jaundice with Molecular Docking / 中国实验方剂学杂志

Objective:To explore the mechanism of treatment of jaundice with Canhuang tablets by molecular docking. Method:The compounds of Canhuang tablets were screened in traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),and targets for treatment of jaundice were collected from the comparative toxicogenomics database(CTD) and DrugBank database.Molecular docking was carry out on the LibDock module of Discovery Studio 2016 software to evaluate the compound-target interaction,and network characteristics were analyzed. Result:A total of 37 compounds in Canhuang tablets had strong interaction on 14 targets,such as pregnane receptor(PXR),constitutive androstane receptor(CAR),farnesoid X receptor(FXR),et al.These targets played an important role in the treatment of jaundice by regulating bilirubin metabolism,regulating bile acid synthesis and transport,inhibiting immune and inflammatory response,and affecting the formation of collagen in the liver.The compound-target network analysis found that moupinamide,canadine,quercetin,demethoxycurcumin,obacunone,curcumin,corchoroside A,berlambine,alnustone,naringenin were the possible main active compounds of Canhuang tablets,which could interact with more than 7 targets. Conclusion:Molecular docking reveals the possible active compounds and the mechanism of treatment of jaundice with Canhuang tablets,and which is conducive to improvement of quality control standard of this preparation and study of its mechanism for jaundice.

Effects of Naoluo Xintong Decoction on vascular dementia rats' memory and learning, and hippocampal neuronal intracellular calcium concentration / 中成药

AIM To study the effects of Naoluo Xintong Decoction (NLXTD) on vascular dementia (VD)rats' memory and learning,and hippocampal neuronal intracellular calcium concentration.METHODS Rats were divided randomly into model group,NLXTD group (8.54 g/kg),Huperzia-A group (0.06 mg/kg) and sham group.They were made into vascular dementia rats by the improved bilateral carotid artery ligation method (2-VO)thereafter if necessary.After one-month corresponding intragastric administration,the rats were ethologically evaluated by the Morris water maze experiment;their fluorescence intensity of hippocampal neuronal intracellular calcium concentration was determined by flow cytometry,and the expression levels of calcitonin gene related peptide (CGRP) and its hippocampus receptor were detected by enzyme-linked immunosorbent assay (ELISA).RESULTS Compared with the model group,rats in NLXTD group displayed overall superiority to those of the model group in terms of significantly shortened time of escape latency (P ＜0.01),significantly increased number through the platform and the times in the fourth quadrant (P ＜ 0.01),a lower fluorescence intensity indicating a lower hippocampal neuronal intracellular calcium concentration (P ＜ 0.05).CONCLUSION The significant improvement of memory and learning observed among VD rats' due to NLXTD intervention may be attributable to its efficacy in reducing the hippocampal neuronal intracellular calcium concentration by enhancing the expression levels of CGRP and its receptor.

Study on prescription screening and preparation process of compound danshen pulse capsule / 中国中药杂志

To develop gastric floating erodible plug pulse capsules with compound Danshen as the model drug, in order to realize the pulse release of traditional Chinese medicines. Through the study on impermeable capsules, optimized prescriptions, drug-containing rapid-release tablets and prescription screening, and erodible plug prescription and process, we successfully prepared compounded Danshen pulse capsule, so as to provide a new dosage form for controlling and treating heart disease to better cater to clinical demands.

Effects of ginseng and ligusticum drug containing serum on the ERK pathway, proliferation, and vitality of neural stem cells undergoing oxygen-glucose deprivation/reoxygenation culture / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effects of ginseng and Ligustrazine drug containing serum on the proliferation, vitality, and extracellular-signal-responsive kinase (ERK) pathway in neural stem cells undergoing in vitro oxygen-glucose deprivation/reoxygenation culture.</p><p><b>METHODS</b>The cultured neural stem cells were randomly divided into 5 groups, i.e., the normal control group (Group A), the oxygen-glucose deprivation/reoxygenation group (Group B), the oxygen-glucose deprivation/reoxygenation +ginseng serum group (Group C), the oxygen-glucose deprivation/reoxygenation + Ligustrazine serum group (Group D), and oxygen-glucose deprivation/reoxygenation +ginseng and Ligustrazine drug serum group (Group E).The protein expression levels of ERK and phosphorylated ERK (p-ERK) were observed using immunoblotting. The proliferation of neural stem cells was observed using 5-bromodeoxyuridine (BrdU) incorporation assay. The vitality of neural stem cells was detected using methyl thiazolyl tetrazolium (MTT) colorimetry.</p><p><b>RESULTS</b>The p-ERK level increased transiently at 10 min and 30 min after reoxygenation, but it decreased to the normal level at 4 h, 6 h, and 1 day, respectively. Compared with Group B, the p-ERK level at 6 h after reoxygenation could be elevated in Group C, D, and E. The proliferation and the vitality of neural stem cells at 1 day after reoxygenation could be enhanced. Furthermore, the effects of combination of ginseng and Ligusticum were better than those of using ginseng or Ligusticum alone.</p><p><b>CONCLUSIONS</b>Combination of ginseng and Ligusticum could promote the proliferation and vitality of rats' neural stem cells undergoing oxygen-glucose deprivation/reoxygenation culture through ERK signal pathway. Its effects was better than that of using ginseng or Ligusticum alone.</p>

Effects of montelukast and BCG-PSN on the expression of STAT5b mRNA and IL-4 mRNA in blood mononuclearcells of rats with asthma / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the expression of signal transducer and activator of transcription 5b (STAT5b) mRNA and interleukin-4 (IL-4) mRNA in blood mononuclearcells in a rat model of asthma and the effect of montelukast (MK) and BCG-polysaccharide and nucleic acid injection (BCG-PSN) on STAT5b mRNA and IL-4 mRNA expression.</p><p><b>METHODS</b>Fifty-two male Sprague-Dawley rats (weight:140-200 g) were randomly divided into four groups: asthma, MK treated and BCG-PSN-treated and control groups. Rat model of asthma was prepared by ovalbumin (OVA) sensitization. The rats were sacrificed 24 hrs after the last sensitization. Blood eosinophils (EOS) were counted. Plasma contens of IL-4 and interferon-gamma (IFN-gamma) were measured using ELISA. Expression of STAT5b mRNA and IL-4 mRNA in blood mononuclearcells was detected with SYBR GREEN I fluorescent quantitation PCR method.</p><p><b>RESULTS</b>Blood contents of STAT5b mRNA and IL-4 mRNA in the untreated asthma group were significantly higher than those in the other three groups (<0.01). Blood EOS count and plasma IL-4 contents in the untreated asthma group significantly increased, while plasma IFN-gamma contents significantly decreased compared with the other three groups (<0.01). There were no significant differences in the parameters measured among the MK-treated, the BCG-PSNjtreated and the control groups. STAT5b mRNA expression was positively correlated to IL-4 mRNA expression, IL-4 content and EOS count (r=0.730,0.650, 0.664, respectively; <0.01), but negatively correlated to IFN-gamma content (r=-0.798; <0.01).</p><p><b>CONCLUSIONS</b>STAT5b mRNA and IL-4 mRNA were strongly expressed in blood mononuclearcells in rats with asthma, and there was a positive correlation between them. MK and BCG-PSN had inhibitory effects on the expression of STAT5b mRNA and IL-4 mRNA, which might be contributed to suppression of airway inflammation in asthma.</p>

hTERT gene expression in children with beta-thalassemia major / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Human telomerase reverse transcriptase (hTERT) is a rate-limiting enzyme which dictates the activity of human telomerase and thus decides the life span of cells. The aim of this study was to explore the expression of hTERT in bone marrow from children with beta-thalassemia major and the relationship between the expression of hTERT and hemoglobin levels.</p><p><b>METHODS</b>Multiple allele specific polymerase chain reaction (MASPCR) was used for targeted DNA amplification and gene mutation analysis of beta-thalassemia. hTERT mRNA expression in bone marrow was examined using real-time reverse transcription polymerase chain reaction (RT-PCR) analysis in 29 children with beta-thalassemia major, in 10 children with agranulocytosis and in K562 cell line. The hemoglobin levels in peripheral blood were measured. The relationship between hTERT expression and hemoglobin levels was evaluated by the Spearman test in the beta-thalassemia major group.</p><p><b>RESULTS</b>hTERT mRNA expression significantly increased in bone marrow from children with beta-thalassemia major compared with that from children with agranulocytosis (0.2928+/- 0.0838 vs 0.0993+/- 0.0336; P<0.01), but was significantly lower than that in K562 cell line (0.8291+/- 0.0908) (P<0.01). A significantly inverse correlation was found between hTERT mRNA expression and hemoglobin levels (r=-0.841, P<0.01).</p><p><b>CONCLUSIONS</b>A low hemoglobin concentration might contribute to the up-regulation of marrow hTERT expression in children with beta-thalassemia major.</p>

Foundation Item: Supported by national science foundation of China(30470598)Neuroprotective Effects of Edaravone on Neonatal Mice with Hypoxia-Ischemia Brain Damage / 实用儿科临床杂志

ObjectiveTo evaluate the neuroprotective effect and possible mechanisms of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) in neonatal Harlequin (Hq) mutant mice brain after hypoxia-ischemia brain injury(HIBD) insult.MethodsThe nine-day-old male Hq mutant mouse pups were assigned randomly either edaravone (n=16) and vehicle (n=17) treatment group. The Hq mice were subjected to left common carotid artery occlusion combined with inhalation 100 mL/L oxygen for 45 minutes. The mice were injected intraperitoneally either with edaravone (10 mg/kg) or equivalent volume of saline immediately after artery occlusion and after hypoxia. Nitrotyrosine and lipid peroxidation formation were evaluated at 3 h and 24 h after hypoxia-ischemia(HI) by using immunohistochemistry staining. Nitrotyrosine formation and caspases activation were evaluated either by immunoblotting or fluorogenic activity measurement at 24 h after HI. Brain injury was evaluated at 72 h by neuropathological score and calculating the infarct volume.ResultsBrain injury encompassed cortex, hippocampus, striatum and thalamus. Edaravone treatment reduced brain injury significantly in all the brain regions. The total infarct volume was reduced 52.8% in edaravone treatment group compared with vehicle group (P<0.001). The edaravone treatment reduced nitrotyrosine formation as well as lipid peroxidation formation significantly, but without obviously effect on caspases activation.ConclusionEdaravone affords neuroprotection after neonatal HI insult, which correlated with the reduction of free radical formation.

Changes of cell proliferation and differentiation in the developing brain of mouse / 神经科学通报·英文版

<p><b>OBJECTIVE</b>To investigate the cell proliferation and differentiation in the developing brain of mouse.</p><p><b>METHODS</b>C57/BL6 mice were divided into 3 groups at random. Bromodeoxyuridine (BrdU) was injected into the brains in different development periods once a day for 7 d. The brains were retrieved 4 weeks after the last BrdU injection. Immunohistochemical and immunofluorescent studies were carried out for detecting cell proliferation (BrdU) and cell differentiation (NeuN, APC, Iba1, and S100beta), respectively.</p><p><b>RESULTS</b>The number of BrdU labeled cells decreased significantly with the development of the brain. Cell proliferation was prominent in the cortex and striatum. A small portion of BrdU and NeuN double labeled cells could be detected in the cortex at the early stage of development, and in the striatum and CA of the hippocampus in all groups. The majority of BrdU labeled cells were neuroglia, and the number of neuroglia cells decreased dramatically with brain maturation. Neurogenesis is the major cytogenesis in the dentate gyrus.</p><p><b>CONCLUSION</b>These results demonstrated that cell proliferation, differentiation and survival were age and brain region related.</p>

Effect of ligustrazine on expression of Fas/FasL in pulmonary injury induced by ischemia/reperfusion in rabbits / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effect of ligustrazine (LGT) on expression of Fas/FasL mRNA during pulmonary ischemia/reperfusion injury (PI/RI) in the rabbits.</p><p><b>METHODS</b>Single lung ischemia/reperfusion animal model was used in this study. The rabbits were randomly divided into three groups (n = 30, in each): sham operated group (Sham), I/R group (I/R) and I/R + LGT group (I/R + LGT). Changes of several parameters which included apoptotic index (AI), wet to dry ratio of lung tissue weight (W/D) and index of quantitative assessment of histologic lung injury (IQA) were measured at 1h, 3h, 5h after reperfusion in lung tissue. Meanwhile the location and expression of Fas/FasL mRNA were observed. Lung tissue was prepared for light microscopic and electron microscopic ob servation at 1 h, 3 h, 5 h after reperfusion.</p><p><b>RESULTS</b>As compared with group I/R, Fas/FasL mRNA slightly expressed in intima and extima of small pulmonary artery, alveoli, and bronchiole epithelia in group LGT. The values of AI, W/D and IQA showed significantly lower in group I/R + LGT than that in group I/R at 1 h, 3 h, 5 h after reperfusion in lung tissue (P < 0.01 and P < 0.05). Meanwhile, abnormal changes of the lung tissue in morphologically were lessen markedly in group I/R + LGT.</p><p><b>CONCLUSION</b>Ligustrazine has notable protective effects on PI/RI in rabbits by inhibiting Fas/FasL mRNA express in lung tissue and decreasing apoptosis.</p>

Therapy Effect of N-Acetylcysteine on Lipopolysaccharide-Sensitized Neonatal Rat with Hypoxic-Ischemic Brain Damage / 实用儿科临床杂志

Objective To evaluate the effect of N- acetylcysteine(NAC) on lipopolysaccharide (LPS) - sensitized neonatal rats with hypoxic- ischemic brain damage(HIBD) and possible mechanism except the antioxidant. Methods With the total number of 98 Wistar pups at postnatal day 8 of either sex was used in this study. There were 86 pups which were divided into three groups to evaluate the brain injury:vehicle group ( n = 29) ,low dose (25 mg/kg) ( n = 31 ) and high dose NAC (200 mg/kg) ( n - 26) treatment group. The pups were injected with LPS(0.1 mg/kg)intraperitoneally 3 days before hypoxic- ischemic(HI) insult. Multiple dose of NAC (25 mg/kg or 200 mg/kg) or vehicle was injected intraperitoneally before and after HI. Brain injury was evaluated 7 days after HI. For the Caspase - 3 activity and immunoblotting analysis, the samples were collected at 24 h after HI treated either with vehicle or high dose NAC ( n = 6 per group). Results The brain injury volume was significantly reduced by high dose NAC (200 mg/kg) treatment compared with that of vehicle (77% reduction, P ＜ 0.001 ). The tissue loss was reduced 67 % ( P ＜ 0.001 ) in high dose NAC treated group compared with that of vehicle. However,there was no significant reduction of brain injury in the low dose NAC treatment group compared with vehicle group. Caspase - 3 like activity measurement showed that the activity decreased 53 % after high dose NAC treatment ( P ＜ 0. 001 ) compared with that of vehicle treatment. The immunoblots showed that the active form of Caspase - 3, 17 kDa band, was abolished by the high dose NAC treatment. Conclusions NAC treatment attenuate LPS - sensitized neonatal HI brain injury is dose dependent. The neuroprotective effect involves Caspase - 3 inhibition.

Developmental changes of glutamate acid decarboxylase-67 in mouse brain after hypoxia ischemia / 神经科学通报·英文版

Objective To study the developmental changes of glutamic acid decarboxylase-67 (GAD-67, a GABA synthetic enzyme) in normal and hypoxic ischemic (HI) brain. Methods C57/BL6 mice on postnatal day (P) 5, 9, 21and 60, corresponding developmentally to premature, term, juvenile and adult human brain were investigated by using both Western blot and immunohistochemistry methods either in normal condition or after hypoxic ischemic insult. Results The immunoreactivity of GAD-67 was up regulated with brain development and significant difference was seen between mature (P21, P60) and immature (P5, P9) brain. GAD-67 immunoreactivity decreased in the ipsilateral hemisphere in all the ages after hypoxia ischemia (HI) insult, but, significant decrease was only seen in the immature brain. Double labeling of GAD-67 and cell death marker, TUNEL, in the cortex at 8h post-HI in the P9 mice showed that (15.6 +/- 7.0)%TUNEL positive cells were GAD-67 positive which was higher than that of P60 mice. Conclusion These data suggest that GABAergic neurons in immature brain were more vulnerable to HI insult than that of mature brain.

Expression of p53 in neonatal mice following hypoxia-ischemia and effects of its inhibitor on neonatal brain injury / 中国当代儿科杂志

<p><b>OBJECTIVE</b>p53-induced apoptosis is crucial in the development of hypoxic-ischemia (HI) brain damage and neurodegenerative disorders. Some experimental research has shown that a synthetic inhibitor of p53 can protect neurons against apoptosis. This study aimed to explore the expression of p53 in neonatal mice following HI brain damage and the effect of p53 inhibitor (pifithrin-alpha, PFT-alpha) on brain damage.</p><p><b>METHODS</b>HI was induced in 9-day-old mice pups by ligation of left carotid artery and 10% oxygen exposure for 55 minutes. The pups were sacrificed and the brains were taken out at 3, 8, 24, and 72 hrs post-HI. The brains were sectioned and stained with antibody against p53 and microtubule-associated protein 2 (MAP-2). PFT-alpha was injected intraperitoneally: in experiment 1, immediately after HI with different dosages (1, 2 and 8 mg/kg); in experiment 2, 2 mg/kg at different HI times (1 hr before HI, and immediately and 1 hr after HI). Control animals without HI received injections of 0.5% dimethyl sulfoxide. Brain damage was evaluated by gross morphology scoring at 72 hrs after HI.</p><p><b>RESULTS</b>The number of p53 positive cells in the cortex, hippocampus and striatum of the ipsilateral hemisphere increased significantly and peaked at 3-8 hrs post-HI when compared with those of contralateral hemisphere as well as normal controls. The positive cells distributed mainly in the MAP-2 negative area. Both different dosages and different injection time PFT-alpha treatment did not reduce the extent of brain damage.</p><p><b>CONCLUSIONS</b>The immunoactivity of p53 increased significantly as early as 3 hrs post-HI. The distribution area of p53 expression was consistent with that of brain damage. The p53 inhibitor PFT-alpha has no protective effects against HI brain damage in neonatal mice.</p>

Neuroprotective effect of hypothermia on hypoxic-ischemic brain injury in mice / 中国当代儿科杂志

<p><b>OBJECTIVE</b>The study was to investigate the effect of different temperatures during hypoxia on brain injury in mice of different ages.</p><p><b>METHODS</b>Newborn C57/BL6 mice at 7 days or 21 days of life were subjected to left carotid artery ligation followed by exposure with 10% oxygen. The mice were kept in a incubator with a predetermined, constant temperature, either 34 degrees centigrade (Hypothermia group) or 36 degrees centigrade (Normothermia group). Brain injury was evaluated 7 days after hypoxia-ischemia (HI). Active caspase-3 and apoptosis-inducing factor (AIF) expressions in the brain tissue were detected by immunohistochemistry and Western Blot was used to evaluate the phosphor-Akt (P-Akt) expression in the brain tissue at 24 hrs post-HI.</p><p><b>RESULTS</b>Brain injuries, including the cortex, hippocampus, striatum and thalamus injuries, occurred in the Normothermia group at 7 days post-HI. The brain cortex showed cystic cavitation in the postnatal day (P)7 pups mice and laminar infarct of the brain cortex was observed in P21 mice. In the Hypothermia group, the P7 mice did not present with laminar infarct of the cortex and had lower scores of neuropathological lesions in cortex, hippocampus, striatum and thalamus than P7 mice from the Normothermia group (P < 0.01); the cortex injuries were significantly relieved but the injuries of hippocampus, striatum and thalamus in P21 mice were similar to those from the Normothermia group. Active caspase-3 (7.0 +/- 5.6) and AIF positive cells (3.7 +/- 6.2) in the cortex of P7 mice from the Hypothermia group were significantly lower than those of the Normothermia group (51.5 +/- 23.2 and 31.8 +/- 22.4) at 24 hrs post-HI (P < 0.01). Wetstern Blot showed the P-Akt expression was obviously decreased in the ipsilateral hemisphere to the occlusion compared with that of the contralateral hemisphere after HI in the Normothermia group (P < 0.05), while in the Hypothermia group the P-Akt expression was not significantly different between the two hemispheres.</p><p><b>CONCLUSIONS</b>Hypothermia has protective effects against HI insults. The protection was more pronounced for the immature brain than the mature brain.</p>

Antineoplastic effect of valproic acid and trichostatin on HL-60 and K562 cells / 中国实验血液学杂志

The objective of this study was to investigate antineoplastic effects of valproic acid (VPA) and trichostatin (TSA) on HL-60 and K562 cells in vitro, and the synergic effects of VPA or TSA in combination with ATRA. The inhibitory effects of VPA, TSA and ATRA in various concentrations and different combinations on proliferation of HL-60 and K562 cells were observed by cell growth curves, 50% inhibitory concentration (IC(50)), as well as inhibition of leukemia colony growth at different time points. The characteristics of cell differentiation or apoptosis were analyzed by cytochemical staining, differentiation antigen detection, cell cycle assay and A(NBT)/A(MMT) value determination. The results showed that HL-60 cell had a lower IC(50) of VPA and TSA compared with K562 cells. ATRA could significantly enhance the inhibition of VPA, TSA on clonegenicity of HL-60 cells and inhibition of VPA on clonegenicity of K562 cells. HL-60 cells treated with VPA displayed the phenotype of neutrophilic like cells, and showed the increases of NBT reduction rate and CD11b expression. No evidence for K562 differentiation was found. It is concluded that both VPA and TSA inhibit HL-60 cells growth in vitro. VPA induces differentiation of HL-60 cells to granulocyte. VPA and TSA have a moderate anti-proliferative effect on K562 cells. None of these agents induces K562 cell differentiation.

Cytochrome C release and apoptosis in neonatal rat cerebral hypoxia-ischemia / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the relation of cytochrome C release from mitochondria to cytosol and neuronal apoptosis after cerebral hypoxia-ischemia (HI) in neonatal rats.</p><p><b>METHODS</b>Hypoxia-ischemia was induced in 7-day-old rat pups by ligation of left carotid artery and 7.7% oxygen was inhaled for 55 min. The pups were sacrificed and the brains were taken out at different recovery time. Some of the brains were homogenized and cellular fraction of mitochondria and cytosol was isolated with different speed centrifugation. The cellular fraction was used for Western blotting. Some of the brains were sectioned and stained with antibody against cytochrome C and TUNEL as well as double labeling with different combinations.</p><p><b>RESULTS</b>Western blots showed that cytochrome C in mitochondria was not reduced significantly at 1 h, but reduced markedly at 14 h in ipsilateral hemisphere post-HI. However, the immunoreactivity of cytochrome C in cytosol was increased markedly at 1 h post-HI and reached peak at 14 h post-HI. The number of cytochrome C positive cells in the cortex was increased significantly at 1 h (8.4 +/- 1.8/visual field) compared to normal control (1.5 +/- 0.8/visual field) (P < 0.01) and reached peak at 14 h (29.0 +/- 5.2/visual field) post-HI. The number of TUNEL positive cells increased significantly at 1 h post-HI (14 +/- 3/visual field) compared to normal control (1.5 +/- 0.8/visual field) (P < 0.01) and reached peak at 24 h (286 +/- 86/visual field). The double labeling of cytochrome C and active caspase-3 showed that they colocalized well at 3 h after HI. Furthermore, the positive cells showed nuclei condensation. There were more active caspase-3 positive cells at late recovery (24 h and on) after HI. The double labeling of cytochrome C and TUNEL showed only part of Positive cells colocalized. The cells with cytochrome C strong staining showed TUNEL negative or weakly positive. The cells with TUNEL strong staining showed weakly cytochrome C staining.</p><p><b>CONCLUSION</b>Cytochrome C release is one of the early biochemical changes of neuronal apoptosis after hypoxia-ischemia in neonatal rat brain.</p>

Study of Human Telomerase Reverse Transcriptase Gene Expression in Acute Non - Lymphocytic Leukemia Children / 实用儿科临床杂志

Objective To explore the gene expression of human telomerase reverse transcriptase (hTERT)in childhood acute non- lymphocytic leukemia (ANLL) and its clinical implication. Methods Expression of hTERT mRNA was detected in HL - 60 leukemia cell line, 14 ANLL children and 11 healthy children by reverse transcriptase- polymerase chain reaction (RT- PCR). Results hTERT gene was expressed in HL-60 cell line, ANLL children (11/14) and healthy children (2/11). The expression of hTERT gene was observed in all subtypes of ANLL. Furthermore, there were statistically significant differences in expression levels of hTERT gene between children with ANLL and healthy children (t = 5.034 P = 0). Conclusions The up - regulation of gene expression of hTERT may play a very important role in the progression of children ANLL. The detection of hTERT expression may be a useful additional method for monitoring the state of illness.