BACKGROUND: As the damage caused by protein glycation is one of the mechanisms of diabetes, it is helpful to treat diabetes related diseases with the understanding of the inhibition of berberine on protein glycation and the protection to the brain damage caused by protein glycation.OBJECTIVE: To observe the effects of berberine on glycated brain damages induced by D-galactose in model rats.DESIGN: Randomly grouping paralleled control study.SETTING: Department of Ophthalmology, Xiamen Traditional Chinese Medicine Hospital.MATERIALS: The experiment was conducted in the Department of Pharmacology, Pharmacy College of Jinan University from June to October 2005. Ninety SD rats (6 weeks old) were selected and divided into 6 groups: control group, model group, hydrochloride aminoguanidine group and high (300 mg/kg), middle (150 mg/kg) and low (75 mg/kg) doses berberine groups with 15 rats in each group. The glycated models were established by intraperitoneal injection of D-galactose. The main drugs:berberine was from Guangzhou Wanji Drugs Limited Company; D-galactose was from Shanghai Yuanju Bioscience Technology Limited Company.METHODS: The rats in the control group were intraperitoneally injected the normal saline for 8 weeks; rats in other groups were injected 5%D-galactose (150 mg/kg) for 8 weeks. From the 3rd week, the hydrochloride aminoguanidine group was infused hydrochloride aminoganidine (150 mg/kg); the three doses berberine groups were given corresponding doses berberine; the control group and model group were given distilled water for 6 weeks with the volume of 10 mL/kg. At the end of the 8th week, the erythrocyte aldose reductase activity was determined by coomassie brilliant blue method; the level of plasma glycohemoglobin was measured by thio-barbituric acid colorimetry and the fructosamine in serum was measured by nitroblue tetrazolium colorimetry. The quantity of advanced glycation end products (AGEs) in serum, and AGEs, malondialdehyde (MDA), and activity of superoxide edismutase (SOD) in brain tissue and calcium ion in neurons were also dertermined. Moreover, the changes of mitochondria in brain hippocampus cells were observed under electronic microscope.MAIN OUTCOME MEASURES: ① The AGEs, plasma glycohemoglobin, serum fructosamine and aldose reductase activity. ②AGEs in brain tissues. ③Calcium level in brain. ④MDA content and SOD activity in brain tissues. ⑤Changes of mitochondria in hippocampus neurons.RESULTS: All 90 animals were involved in the result analysis. ①Aldose reductase activity and glycated product content in serum: After the rats were treated with D-galactose for 8 weeks, the aldose reductase activity in red blood cells and the content of fructosamine in serum, glycohemoglobin,AGEs in the model group were significantly higher than those in the normal control group (P ＜ 0.01); After treated by high and middle doses berberine for 6 weeks, the activity of aldose reductase and content of fructosamine in serum (absorbancevalue of hemoglobin every 10 g), glycohemoglobin, and AGEs were obviously lower than those in the control group [(1.07±0.39), (1.22±0.47), (1.76±0.30) nkat/g, t=5.052, 5.484, P ＜ 0.01;(0.740±0.142), (0.862±0.131), (0.958±0.083) mmol/L, t=7.829, P ＜ 0.01,t=2.404, P ＜ 0.05; 58.434±12.135, 64.614±13.418, 83.747±7.990,t=4.922, 6.748, P ＜ 0.01; (3.104±0.814), (2.937±0.514), (4.156±0.860) U/mg,t=4.104, 3.440, P ＜ 0.05]; the aldose reductase activity of the low dose berberine group was lower than the model group (P ＜ 0.05), which had no obvious effect on glycated products. ②AGEs in brain tissues: The contents in the hydrochloride aminoganidine group, high and middle doses berberine groups were lower than the model group [(10.52±1.22), (10.95±1.75),(11.95±2.27), (14.26±3.51) U/mg, t=-3.892, -3.263, P ＜ 0.01, t=-2.139,P ＜ 0.05], and the low dose berberine had little effect (P ＞ 0.05). ③Calcium level in neurons: The levels in the hydrochloride aminoganidine group,and high dose berberine groups were lower than the model group.[(271.52±32.71), (293.84±31.58), (337.15±58.49) nmol/L, t=-3.421, P＜ 0.01, t=-2.275, P ＜ 0.05], the low dose berberine group had no obvious effect (P ＞ 0.05). ④MDA content and SOD activity in brain tissues: MDA contents in the hydrochloride aminoganidine group, high and middle doses berberine groups were lower than the model group, and the SOD activity was markedly higher than the model group [(2.09±0.16), (2.12±0.22),(2.41±0.12), (2.54±0.21) μmol/g, t=6.601, 5.348, P ＜ 0.01, t=2.082, P＜ 0.05; (8.79±1.09), (8.80±1.52), (7.90±1.48), (6.48±1.34) mkat/g, t=4.571,4.254, P ＜ 0.01, t=2.226, P ＜ 0.05]. ⑤Mitochondria structure in brain hippocampus cells: Under the electronic microscope, mitochondria in brain hippocampus cells of the model group appeared obvious swelling with broken crests and disorganized structure, even obvious big vacuoles were observed. In the hydrochloride aminoganidine, and high and middle doses berberine groups, no obvious swelling was observed with vacuoles only in a few mitochondria. Nevertheless, obvious swelling appeared in mitochondria of low dose berberine group with broken crest and disorganized structure,and vacuoles were observed.CONCLUSION: D-galactose-induced damage in mitochondria may be related to AGEs formation in brain tissue, maladjustment of calcium ions in neurons and oxidative stress in rat models. Berberine can inhibit glycation induced by D-galactose and protect rat brain tissues from glycated damage.

Objective To explore the clinical effects of high frequency oscillatory ventilation (HFOV) combined with pulmonary surfactant (PS) on neonatal meconium aspiration syndrome (MAS).Methods Data of 53 newborns with MAS admitted into the Neonatal Intensive Care Unit of Ning Bo Women and Children's Hospital from June 2008 to June 2011 were retrospectively analyzed.According to different therapeutic measures,they were divided into three groups:conventional mechanical ventilation (CMV) group (n=23),HFOV group (n=18) and HFOV+PS group (n=12).The oxygen index,arterial oxygen/alveolar oxygen ratio (a/ApO2) and inspired oxygen fraction (FiO2) were monitored at 2,12,24 and 48 h after mechanical ventilation.The mechanical ventilation time,duration of hospital stay,change of symptom,complications and clinical outcomes of the three groups were compared by analysis of variance and Chi-square test.Results The parameters of the three groups at 2 and 48 h after mechanical ventilation were as followed:CMV group [oxygen index:(23.79±7.27) and (15.04±4.76) mm Hg; a/ApO2:0.11±0.04 and 0.31 ±0.07; FiO2:0.74±0.16 and 0.47± 0.21],HFOV group [oxygen index:(21.13±6.29) and (11.73±4.54) mm Hg; a/ApO2:0.14±0.06 and 0.35±0.06; FiO2:0.68±0.14 and 0.41±0.11] and HFOV+ PS group [oxygen index:( 18.35 ± 5.68 ) and ( 7.85 ± 5.06 )mm Hg; a/ApO2:0.17±0.03 and 0.40±0.02; FiO2:0.59±0.13 and 0.29±0.16].Compared with CMV group,the parameters of HFOV group and HFOV+ PS group were different at different time points,and the parameters (duration and extent) of HFOV+ PS group were better than those of HFOV group (all P＜0.05).The mechanical ventilation time was (7.2±0.6) days in CMV group,(4.2± 1.4) days in HFOV group and (2.9±0.5) days in HFOV+PS group; the hospital stay was (22.2±4.5) days in CMV group,(15.6±3.4) days in HFOV group and (11.8±4.3) days in HFOV+PS group; and the oxygen treatment time was (15.4± 2.4) days in CMV group,(11.8±5.3) days in HFOV group and (7.4±2.2) days in HFOV+PS group.The mechanical ventilation time,oxygen treatment time and hospital stay time were the longest in CMV group,the shortest in HFOV+ PS group (P＜ 0.05,respectively).Conclusions Early HFOV combined with PS might be a better therapeutic method for infants with MAS than HFOV or CMV alone.

BACKGROUND: Some researches demonstrate that tea polyphenols (TP) has protective effects on neurotoxicity of hippocampal nerve cells induced byβ-amyloid peptide (Aβ), 6-hydroxydopamine (6-OHDA) and oxidative substances. In addition, clinical preliminary examination indicates that TP plays a certain preventive and therapeutic effects on the reduction of recognition function in high-risk population with Alzheimer disease (AD); however, its target and mechanism are still hot topics.OBJECTIVE: To observe the interfering effects of TP on cerebral nerve cell apoptosis induced by D-galactose and Aβ25～35 in mice.DESIGN: Randomized controlled animal study.SETTING: Department of Pharmacology, Pharmacological College of Jinan University.MATERIALS: The experiment was carried out in the Experimental Center of Jinan University from September 2004 to January 2005. A total of 90 healthy Kumning mice, aged 2 months, each gender in half, weighing 26-28 g, were provided by Guangdong Provincial Medical Laboratory Animal Center. Tea polyphenols was provided by Zhejiang Oriental Tea Science and Technology Corporation (batch number: 20040203); D-galactose by Shanghai Number 2 Reagent Plant (batch number: 20030708); Aβ25～35 by Sigma (batch number: 13/01/2004); vitamin E (Vit-E) by Shanghai Xinyi Pharmaceutical Factory (batch number: 20030708).METHODS: Experimental interference: Mice based on body mass were randomly divided into 6 groups: sham operation group (n =17), model group (n =16), vitamin E group (n =16), low-dose (n =13), moderate-dose (n =14) and high-dose (n =14) tea polyphenols groups. In above-mentioned animals, except those in the sham operation group, all were given 120 mg/(kg·d) D-galactose for 12 consecutive weeks, and Aβ25～35 (4 nmol) was slowly injected into the lateral cerebral ventricle. In sham operation group, the same volume of artificial cerebral spinal fluid (CSF) was internally injected into lateral ventricle. Drug treatment began at the first week. Mice in the sham operation group and model group were given distilled water, and the animals in other groups were given the above-mentioned drugs (100 mg/kg Vit-E, 100, 250 and 625 mg/kg TP), respectively. The volume of perfusion was 10 ml/kg, and the treatment lasted for 12 consecutive weeks. Experimental evaluation: After administration, LW-Ⅱ water maze was used to measure learning and memory condition; brain, liver tissues and serum were obtained to measure activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA); Fura-2/AM loading method was used to measure Ca2+ concentration in erythrocytes and neurons; flow cytometer was used to detect cerebral nerve cell apoptosis.MAIN OUTCOME MEASURES: Cl) Learning and memory ability; (2) SOD activity and MDA content in serum, liver and brain tissues; (3) Ca2+ concentration in erythrocytes and neurons;flow cytometer was used to cerebral nerve cell apoptosis.MAIN OUTCOME MEASURES：①Learning and memory ability;②SOD activity and MDA content in serum,liver and brain tissues；③Ca2+ concentration in erythrocytes and neurons；④cerebral nerve cell apoptosis．RESULTS：All 90 mice were involved in the final analysis．①At 12 weeks after administration,time to swim out of the water maze in the moderete-dose and high-dose TP groups and Vit-E group was shorter than that in the model group,and numbers of errors in passing the blind alleys in the water maze was reduced as compared with those in the model group,and there was significant difference(P＜0．05-0．01)．②SOD activities in the moderate-dose and high-dose TP groups were increased as compared with that in the model group,but MDA content in the high-dose TP group was decreased as compared with that in the model group．There was significant difference(P＜0．05-0．01)．③Ca2+ concentration in erythrocytes and neurons in the modemte-dose and high-dose TP groups and Vit-E group was lower than that in the model group,and there was significant difference(P＜0．05-0．01)．④The rates of brain neurons apoptosis in treatment groups with different doses of TP were 12．6％，18．6％,and 24．1％ respectively, exhibiting significant difference as compared with the mice in sham operation group(P＜0．05-0．01) CONCLUSION：TP can inhibit cerebral nerve cell apoptosis induced by D-galactose and Aβ25～35 and improve learning and memory ability in model mice．The effects may be related to its action of raising general anti-oxidative ability and improvement of intrecellular Ca overload induced by oxidative stress injury．

Background and purpose:Radiomics is an emerging field that generates large amounts of valuable clinical information through extracting quantitative imaging features. The purpose of this study was to use the radiomics approach to assess the value of features captured from PET and CT in predicting the therapeutic effect in stageⅠ non-small cell lung cancer (NSCLC) after stereotactic ablative radiotherapy (SABR).Methods:Patients with stageⅠ NSCLC conifrmed by pathology and treated with SABR were included retrospectively. The gross tumor volume (GTV) was deifned by two radiologists. PET and CT scan images were collected, and radiomic features were further extracted and analyzed. Non-negative matrix factorization was used to distinguish patients with or without local control.Results:Sixteen patients were eligible for analysis. This study identiifed two PET features (LL_GLCM_Maximal_Correlation_Coeffcient and HL_GLRMS_LRE) captured from PET/CT as having signiifcance in classifying patients with or without disease development. This study not ifnd similar results in CT scans.Conclusion:It seems feasible to use radiomics information effects from PET/CT to predict therapeutic effects of SABR in stageⅠ NSCLC. Further investigation is needed.

Objective To perform molecular cloning and sequencing, bioinformatics analysis,protein expression and function of extracellular signal regulated kinase (EgERK1) of Echinococcus granulosus in Xinjiang. Methods The specific primers of EgERK1 were designed and total RNA was extracted from Echinococcus granulosus in Xinjiang. EgERK1 gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and prokaryotic expression plasmid pET28a-EgERK1 was constructed and sequenced. The sequences were analyzed by DNA sequencing and bioinformatics technology. The recombinant EgERK1 protein was induced and expressed. The biological function was detected using sodium dodecyl sulfate polyacrylamide gel electropheresis and Western blot. Results The sequence of RT-PCR product was 1125 bp, encoding 374 amino acids with isoelectric point of 6.34.This gene was a new ERK-homologues gene indicated by BLAST, named EgERK1(EU701008).Homology comparisons indicated that the homology of EgERK1 and EmMPK1from Echinococcus multilocularis was 95.45%, and was 43.04%-61.88% to ERK from Caenorhabditis elegans, S. cerevisiae, D. melanogaster and human. Phylogenetic analysis showed that EgERK1 clustered with EmMPK1. Bioinformatics analysis predicted that EgERK1 contained a highly conserved T-X-Y motif and activation loop segment of ERK-like kinase.Western blot results showed the EgERK1 recombinant protein could reacted specifically with anti-human ERK monoclonal antibody. Conclusion A new EgERK1 gene of Echinococcus granulosus is successfully cloned and its recombinant protein could reacted specifically with ERK1/2 antibody, which provides the basis for further study of EgERK1 function in the host-parasite interaction.