The activation of oncogenes occured in most tumors,and is believed to play an important role in tumorigenesis. However,the activation of oncogenes could induce cellular senescence in wild type cells,known as oncogene-induced senescence (OIS). Thus,the activation of oncogenes has the dual role in inducing cellular senescence or tumorigenesis. DNA damage checkpoint response (DDR) is the molecular signal transduction pathway that delay or arrest cell cycle progression in response to DNA damage and is an important molecular mechanism that induce cellular senescence. Activation of oncogenes could produce DNA damage signals and initiate DDR,which subsequently induce cellular senescence. However,when DDR pathway is deficient,activation of oncogenes could induce unlimited DNA hyper-replication and cellular hyper-proliferation,which results in accumulation of genome instability,and tumorigenesis ultimately. Therefore,the dual role of activated oncogenes is regulated by the integrity of DDR pathway. The key role of DDR in regulating activated oncogenes indicates that maintain or restore the integrity of DDR pathway might provide a new strategy in cancer prevention and therapy.

BACKGROUND: Ephedra, a Chinese medicine, is often used to treat obesity with relatively satisfying results recently. However, the effects of Ephedra on the perimenopausal and postmenopausal obese women remain unclear.OBJECTIVE: To observe the effects of oral Ephedra decoction on body mass and the levels of blood lipids, blood glucose and hormone in ovarietomized obese rats.DESIGN: A completely randomized and controlled experiment.SETTING: Institute of Physiology and Psychology, School of Basic Medical Sciences, Lanzhou University.MATERIALS: The experiment was performed in the Key Laboratory of Pre-clinical Study for New Drugs of Gansu Province and the Laboratory of Institute of Physiology and Psychology, School of Basic Medical Sciences,Lanzhou University from February 2006 to June 2006. Forty-four healthy female SD rats were randomly divided into four groups with 11 rats in each group, namely sham-operated group, ovariectomized group, estrogen replacement therapy group and Ephedra group.METHODS: ① After having been narcotized by cloraminone (110 mg/kg),rats were underwent a bilateral ovariectomy except those in the sham-operated group, which were also operated, but their ovaries were not cut off. ②Rats in the sham-operated group and ovariectomized group were subcutaneously injected with sesame oil (0.2 mL/each rat) every day postoperatively till the end of the experiment. ③ The rats in the estrogen replacement therapy group were given estradiol (1 mg/kg) by subcutaneous injection every day postoperatively till the end of the experiment. ④ The rats in the Ephedra group freely drank 1% water extracts from Ephedra postoperatively, later the concentration of Ephedra gradually increased to 8% on the sixth day, which lasted until the end of the experiment. ⑤ The food intake was monitored daily, and body mass was measured every ten days. ⑥ At the end of the experiment, all the rats were fasted for 12 hours and collected blood samples for the measurement of serum indexes. The body mass and body length were measured to calculate the Lee's index [(g)×103/body length (cm)] at the same time.MAIN OUTCOME MEASURES: ① Body mass and Lee's index at different time points in each group. ② Food intake at different time points in each group. ③ Levels of blood lipids and blood glucose in each group. ④Levels of estrogen, progesterone and insulin in each group.RESULTS: Forty-four rats all entered the analysis of results. ① Result of body mass and Lee's index at different time points: The body masses on the 20th, 30th, 40th and 50th days in the ovariectomized group were (256.4±14.3),(271.3±16.1), (276.4±12.7), (285.7±24.2) g, which were significantly higher than those in the sham-operated group [(226.5±11.5), (241.8±12.6),(243.1±13.5), (251.1±22.4) g, P ＜ 0.05-0.01], and the Lee's index in the ovariectomized group was greater than that in the sham-operated group(317.2±13.5, 280.4±11.2, P ＜ 0.01). The body masses on the 40th and 50th days in the estrogen replacement therapy group were (243.7±14.8) and(246.2±11.9) g, which were significantly lower than those in the ovariectomized group (P ＜ 0.05-0.01), and the Lee's index (289.9±13.5) was lower than that in the ovariectomized group (P ＜ 0.01). The body masses on the 40th and 50th days in the Ephedra group were (245.4 ±14.1) and(252.4±14.9) g, and the Lee's index was 294.4±11.0, which were all lower than those in the ovariectomized group (P ＜ 0.05). ② Result of Food in take at different time points: The food intakes on the 30th, 40th and 50th days in the Ephedra group were (17.8±2.4), (22.3±3.9), (26.1±3.5) g per day,which were decreased as compared with those in the ovariectomized group[(25.9±4.7), (28.5±5.3), (32.8±5.5) g per day, P ＜ 0.05]. ③ Levels of blood lipids and blood glucose: The levels of triglyceride, cholesterol and low density lipoprotein cholesterol (LDL-C) in the ovariectomized group were (1.73±0.32), (1.45±0.50), (0.78±0.19) mmol/L, which were higher than those in the sham-operated group [(0.94±0.29), (1.05±0.30), (0.08±0.11) mmol/L, P ＜ 0.01]. After the estrogen replacement therapy, the levels of triglyceride, cholesterol, LDL-C and blood glucose were (1.10±0.34),(1.14±0.30), (0.17±0.05), (5.88±1.21) mmol/L, which were lower than those in the ovariectomized group (P ＜ 0.05-0.01), but the level of high density lipoprotein cholesterol (HDL-C) was higher than that in the ovariectomized group [(1.11±0.31), (0.88±0.21) mmol/L, P ＜ 0.05]. The levels of triglyceride, cholesterol, LDL-C and HDL-C in the Ephedra group were (0.97±0.16), (1.11±0.20), (0.59±0.07) and (0.45±0.061) mmol/L, which were lower than those in the ovariectomized group (P ＜ 0.05-0.01). ④ The serum levels of estrogen, progesterone and insulin in each group: The serum levels of estrogen and progesterone in the ovariectomized group were lower than those in the sham-operated group [(17.09±9.00), (28.51 ±7.99) μg/L;(58.69±12.11), (62.73±10.93) μg/L, P ＜ 0.01], the serum level of insulin was higher than that in the sham-operated group [(31.74±6.69),(23.75±6.66) mU/L, P ＜ 0.01]. The serum levels of estrogen in the estro gen replacement therapy and Ephedra group were (36.03±8.83) and (30.18±8.61) ng/L, which were higher than those in the ovariectomized group(P ＜ 0.05-0.01), the level of insulin were (21.34±4.57), (24.86±6.20) mU/L,which were lower than those in the ovariectomized group (P ＜ 0.05-0.01).The serum level of progesterone in the Ephedra group [(17.68±6.19) μg/L]was lower than that in the ovariectomized group (P ＜ 0.01).CONCLUSION: Ephedra can promote loss of body mass, reduce levels of the blood lipids and insulin, and increase the serum levels of hormones in ovariectomized obese rats.

Objective To investigate the protective effect of prenatal astaxanthin treatment against cognitive impairment in adult offspring induced by exposure to maternal seizures in utero.Methods Female adult Sprague-Dawley rats were randomly divided into four groups:control group,astaxanthin group,kindling group and kindling+astaxanthin group.Each rat was implanted with electrodes.Those in the kindling and kindling+astaxanthin groups were kindled once a day by electrical stimulation of the amygdala.All rats were allowed to mate after one week's amygdala kindling.Rats in the kindling and kindling+astaxanthin groups continued to be treated with electrical stimulation every 48 hours from gestational day 1 to 20,and those in the astaxanthin and kindling+astaxanthin groups were injected intraperitoneally with 30 mg/(kg · d) of astaxanthin simultaneously.Naturally delivered offspring were raised till 12 weeks of age.Morris water maze test was performed to assess the cognitive function of adult offspring.Changes in the morphology of hippocampus were observed with Nissal's staining and transmission electron microscope.Expression of cyclic adenosine monophosphate response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in adult offsprings' hippocampus tissues at protein and mRNA levels were determined using Western-blotting and reverse transcription-polymerase chain reaction.Analysis of variance and LSD test were used as statistical methods.Results Morris water maze test showed that from the 3rd day to the 5th day,the kindling group had significantly longer escape latency [(36.33 ±7.85),(28.80± 8.41),(29.50± 11.72) s] than the control [(28.90±7.46),(17.59±9.12),(10.40±3.69) s] and kindling+astaxanthin groups [(28.30±5.75),(18.37±3.39),(15.23±6.63) s] (F=3.601,9.811 and 14.226,all P＜0.05).In probe trials,the kindling group had significantly fewer platform crossings as compared with the control and kindling+astaxanthin groups [(4.40± 1.71) vs (7.20± 1.62) and (6.50±1.84) times,F=6.586,P=0.001].The kindling group spent dramatically less time in the target quadrant than the control and kindling+astaxanthin groups [(27.35±7.63) vs (58.29± 10.48) and (40.41 ± 7.06) s,F=25.825,P＜0.001].Nissl staining showed that hippocampal neurons of offspring in the control group were normal,but there was hippocampal damage in the kindling group and the damage was more severe than that in the kindling+astaxanthin group.Electron microscope observation showed that neurons and synapses in the hippocampal CA1 area of offspring in the control group were normal.However,obvious damage to neurons and synapses was induced in the kindling group and that was worse than the damage induced in the kindling+astaxanthin group.Expression of CREB and BDNF protein in the kindling group (0.19±0.06and 0.32 ±0.04,respectively) were significantly lower than those in the control (0.81 ±0.11 and 0.93 ± 0.04,respectively) and kindling+astaxanthin groups (0.60± 0.07 and 0.80±0.06,respectively) (F were 34.015and 71.074,both P＜0.001).Moreover,the kindling group showed decreased expression of CREB and BDNF mRNA (0.48 ± 0.11 and 0.43± 0.08,respectively) as compared with the control (1.02± 0.65 and 0.99± 0.09,respectively) and kindling+astaxanthin groups (0.89±0.15 and 0.96±0.13,respectively) (F were 13.447 and 21.912,both P＜0.01).Conclusion Treatment with astaxanthin could ameliorate the cognitive impairment and pathological damage in hippocampus of adult offspring induced by exposure to maternal seizures in utero through regulating the CREB-BDNF signal pathway.

Objective To evaluate the effect of oxycodone on function of GABAA receptors in dor-sal root ganglion ( DRG ) neurons of rats with neuropathic pain ( NP ) . Methods Thirty-six adult male Sprague-Dawley rats, weighing 180-220 g, aged 10 weeks, were allocated into 3 groups ( n=12 each) u-sing a random number table method: sham operation group ( group S ) , group NP and oxycodone group ( group O) . The sciatic nerve was only isolated but not ligated in group S. NP was induced by chronic con-striction injury. The sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 chromic catgut. Oxycodone 15μg∕kg was intraperitoneally injected once a day for 14 con-secutive days from ligating the sciatic nerve to satisfaction in group O. The thermal paw withdrawal latency( TWL) was measured at 1 day before establishing the model ( T0 ) and 3, 5, 7, 10 and 14 days after es-tablishing the model ( T1-5 ) . The rats were sacrificed after measurement of pain threshold at T5 , and DRG neurons were acutely isolated for recording the amplitude of GABAA receptors-activated currents using whole-cell patch-clamp technique. Results Compared with group S, the TWL was significantly shortened at T1-5, and the amplitude of GABAA receptors-activated currents in DRG neurons was decreased in NP and O groups (P<0. 05). Compared with group NP, the TWL was significantly prolonged at T1-5, and the ampli-tude of GABAA receptors-activated currents in DRG neurons was increased in group O ( P<0. 05) . Conclu-sion Oxycodone can enhance the function of GABAA receptors-activated currents in DRG neurons and thus enhance GABAA receptors-mediated presynaptic inhibition, which may be related to the mechanism of oxyc-odone-induced reduction of NP in rats.

Objective To initially establish an occupational well-being questionnaire for Chinese clinical nursing staffs.Methods The draft questionnaire,including open-ended questions and semi-structured interview,was established according to literature review and revised after expert′s consultation and pilot survey. Then,the questionnaire was tested by 460 nurses who randomly selected from a Class Ⅲ Grade Ⅰ hospital in Wuhan province from September 201 4 to June 201 5.The reliability and validity of the questionnaire were examined by exploratory factor principal component analysis,confirmatory factor analysis of maximum likelihood estimation method,and the Cronbach′s αanalysis.Results The questionnaire contained 1 9 items belonging to 5 dimensions that included welfare,value,interpersonal relationship,leaders and characteristics.The Cronbach′sαcoefficient for the questionnaire and each dimensions were 0.91 4 and 0.753-0.862.The correlation coefficients between each items and the total score as well as its related dimension were 0.487-0.729 and 0.709-0.883.The accumulative contribution rate of the five factors was 71 .1 05%.Conclusions The nurses′occupational well-being questionnaire is a reliable and valid instrument to assess the occupational well-being for clinical nursing staffs.

Objective To construct training course for specialized wound nurses based on Delphi method. Methods Firstly, the consultation list on context of training course for specialized wound nurses was designed by self between January 2015 to May 2015. The expert consultation involving eleven clinical nurse specialists, ten nursing managers, four nursing teachers from fifteen cities of provinces was performed via three rounds to determine the content of training course for specialized wound nurses. Results The content determined of training course for specialized wound nurses included three indicators in level one ( course components) involving professional attitude, knowledge and skills, 14 indicators in level two ( course name) involving medical ethics value of wound nursing, history of wound nursing, importance of specialized wound nurses and so on, 58 indicators in level three ( course context) involving personal and family burden caused by chronic wounds, development situation of wound nursing in China, working pattern of specialized wound nurses, professional development requirements and so on. Conclusions The context of training course for specialized wound nurses is determined from three dimensions including professional attitude, knowledge and skills. Besides, this study provides suggestions and theoretical support for the training of specialized wound nurses.

Objective To analyze the magnetic resonance imaging (MRI) of the spinal cord and clinical characteristics in patients with autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.Methods A total of 1 040 samples of cerebrospinal fluid (CSF) and sera collected in the Second Affiliated Hospital of Guangzhou Medical University from March 2013 to June 2018 were tested with tissue-and cell-based assays,and 42 patients were found positive for GFAP-IgG.The clinical data and MRI characteristics of the spinal cord of 19 patients who were positive for GFAP-IgG in CSF with autoimmune GFAP astrocytopathy and lesions in the spinal cord were retrospectively reviewed.Results There were 12 females and seven males among the 19 patients,with onset age of (44±17) years.The main manifestations of these patients included limb weakness (14/19),abnormal vision (5/19),headache (4/19),seizure (4/19),dementia (3/19),etc.On MRI of the spinal cord,five patients showed involvement in the cervical cord alone,eight showed involvement in the thoracic cord alone and six had both cervical and thoracic segment involvement.Fifteen patients had longitudinally extensive myelitic abnormalities (≥3 vertebral segments long).Seven enhancement patterns were encountered.Lesions were displayed in the spinal cord and brain in eight patients.Central gray matter involvement in the spinal cord was found in all the 19 patients.Conclusions Autoimmune GFAP astrocytopathy more frequently presents in females than in males.MRI of the spinal cord has complex presentations and longitudinally extensive myelitic abnormalities usually.Patients often show central gray matter involvement in the spinal cord.Myelitic abnormalities present more often in thoracic segment than in cervical segment.Abnormalities in lumbar segment are less encountered.

Objective:Regulatory quantitative trait loci (regQTL) theory can help to evaluate the regulation function of single nucleotide polymorphisms (SNPs) on crucial biological signals from a three-dimensional perspective. The aim of this study was to investigate the effect of these regQTL-SNPs on the susceptibility of lung cancer.Methods:Based on the regQTL theory, using the database of identified lung cancer regQTL-SNPs, we screened the SNPs that may function as regQTL in the reported susceptible regions of lung cancer by genome-wide association study(GWAS), and a two-stage case-control study was conducted (screening stage: 2 331 lung cancer cases and 3 077 healthy controls; validation stage: 626 lung cancer cases and 667 healthy controls) to definite the association of related regQTL-SNPs with the susceptibility of lung cancer.Results:A total of 8 regQTL-SNPs were screened in the reported susceptible regions of lung cancer by GWAS. Among which, 3 SNPs were significantly associated with the risk of lung cancer ( P<0.05) in the screening stage. Further validation results indicated that the variant T allele of rs6998591 in ADRA1A was significantly associated with increased risk of lung cancer (additive model: OR=1.33, 95% CI:1.01-1.74, P=0.040). In addition, the variant G allele of rs11202916 in ACTA2 was significantly associated with decreased risk of lung cancer (recessive model: OR=0.71, 95% CI:0.52-0.96, P=0.026). Stratified analysis indicated that the variant T allele of rs6998591 significantly increased lung squamous cell carcinoma risk (additive model: OR=1.53, 95% CI: 1.01-2.32, P=0.043), while the variant G allele of rs11202916 significantly decreased lung adenocarcinoma risk (additive model: OR=0.83, 95% CI: 0.69-0.98, P=0.031). Gene-environment interaction analysis indicated that the risk of developing lung cancer increased by 235% in smoking individuals carrying rs6998591 variant T allele compared with those non-smoking individuals carrying no rs6998591 variant T allele( OR=3.35,95% CI:2.10-5.34, P<0.001). Conclusion:There are two regQTL-SNPs that could significantly affect the susceptibility of lung cancer in the GWAS reported susceptible regions of lung cancer.

Objective:To understand the effect of vitamin B1 on lymphocyte function in simulated microgravity.Methods:Splenocytes of mice were isolated,and the rotatary cell culture system was used to simulate microgravity.Lymphocytes were stimulated with mitotic agents Concanavalin A,and cells were treated with different concentrations of vitamin B1,proliferation indexes of lympho-cytes and levels of cytokines in supernatant were detected.Results:Simulated microgravity could inhibit proliferation of splenic lym-phocytes,and decrease levels of cytokines,while vitamin B1 could promote lymphocyte proliferation and cytokines production in cells cultured in simulated microgravity in a dose dependent manner.Conclusion:Vitamin B1 may attenuate the inhibitory effect of simulated microgravity on lymphocytes by regulating cell proliferation and secretion of cytokines.

0.05 ). After once injection both observers considered the number of clearly recognized endocardial border segments increased significantly. The number evaluated by observers A increased from 2.68 ? 0.95 to 5.99 ? 0.10 while from 2.82 ? 1.03 to 5.99 ? 0.11 by observers B( P 0.05 ). The average contrast enhancement rate of LV endocardial border was 99.7 %. Perfluoropropane-albumin microsphere injection had no significant effection on vital signs such as blood prssure, heart rate and respiration. Electrocardiogram didn′t change markedly and the variance of the laboratory findings like blood and urine routine examination, hepatic and renal function was in normal range. Only one case( 0.33 %) had slight side-effects who suffered from mild nausea and diarrhea, which suggested the clinical safety of this contrast agent. Conclusions Perfluoropropane-albumin microsphere injection could enhance the resolution of LV endocardial borders and make the judgement of regional myocardial movement easier. It has little side-effects and will be appropriate for clinical use.