Objective To investigate the mechanism of the protective effects of olanzapine against apoptosis of PC12 cells induced by ?-amyloid peptide 25-35 (A?_ 25-35 ). Methods Based on the model of apoptosis of PC12 cells induced by A?_ 25-35 , cell viability was determined by MTT assay. The expressions of Bax, Caspase-3 of PC12 cells induced by A?_ 25-35 and olanzapine were assessed by Western blot. Results 10 -14 -10 -5 mol/L A?_ 25-35 lowered the cell viability of PC12 cells, 50?mol/L and 100?mol/L olanzapine pretreatment enhanced the cell viability of PC12 cells, and there was significant difference compared with olanzapine non-pretreated groups (P

Objective Brain -derived neurophic factor ( BDNF) has played an important role in the repair of cauda equina Injury.The aim of this article was to observe the influences of Miao medicine Sheng Xian Decoction on structural change and BDNF protein expression in the sacral spinal cord of rats with cauda equina injury . Methods The rat model of cauda equina injury was es-tablished by using nerve clamping .Rats were randomly divided into the following groups:normal group , control group , Miao medicine group and mecobalamin group , 15 rats in each group .According to the death time after modeling , the rats in each group were subdivi-ded into 1d group, 7d group and 14d group, 5 in each subgroup.The nerve function recovery of rats in every group was observed through Basso , Beattie & Bresnahan locomotor rating score ( BBB score ) .The structural change of sacral spinal cord was observed(11.40 ±1.14) and the mecobalamin group (11.40 ±0.89) (P>0.05).On the 7th, 14th day after modeling, the scores of the Miao medicine group (17.0 ±1.00, 19.60 ±0.55) and the mecobalamin group (16.2 ±0.84, 18.80 ±0.84) were much higher than the control group (14.00 ±0.70, 16.40 ±0.55) (P<0.05).There was no significant difference between the Miao medicine group and the mecobalamin group (P>0.05).The scores of the control group , the Miao medicine group and the mecobalamin group showed an increasing tendency with time, and the difference of scores among the groups are of statistical significance (P<0.05).HE staining:Compared with the normal group , the spinal cord structure of the control group was damaged and glial cell proliferation increased signif -icantly.Compared with the control group , rats in the Miao medicine group and the mecobalamin group were lightly damaged in spinal cord and got improvement in the glial cell proliferation as well as an increase in the number of normal neurons .Immunohistochemistry staining:On the 1st day after modeling, the MOD values of the control group (0.152 ±0.007) , the Miao medicine group (0.156 ± 0.008) and the mecobalamin group (0.162 ±0.008) were much higher than that of the normal group (0.130 ±0.006), and the difference was of significant difference (P<0.05).Moreover,the MOD value of the mecobalamin group was much higher than those of the control group and the Miao medicine group , which was of significant difference (P<0.05); there was no statistical significance between the control group and the Miao medicine group (P>0.05).On the 7th and 14th day after modeling, the MOD values of the Miao medicine group (0.205 ±0.009, 0.183 ±0.008) and the mecobalamin group (0.217 ±0.033, 0.187 ±0.007) were much higher than that of the control group (0.181 ±0.007, 0.161 ±0.014), which was of significant difference (P<0.05).There was no statistical significance between the values of Miao medicine group and the mecobalamin group (P>0.05).The MOD values of the control group , the Miao medicine group and the mecobalamin group showed a tendency of increase followed by decrease with time .The MOD values of 3 subgroups in the Miao medicine group and the mecobalamin group had no statistical significance (P>0.05).The MOD value of 14d subgroup was much lower than 7d subgroup in the control group (P<0.05), however, compared with 1d subgroup in the control group, there was no significant difference (P>0.05).There was no significant difference among the MOD value of 3 subgroups in the normal group (0.130 ±0.006, 0.130 ±0.006, 0.130 ±0.008) (P>0.05). Conclusion Miao medicine Sheng Xian Decoction can promote neuron survival and improve nerve functions through increasing the BDNF expression in the sacral spinal cord of rats with cauda equina injury .

Humidificait on by artificial means must be provided when the upper airway is bypassed during mechanical ventilation.Enough humidification is very important during mechanical ventilation.Heated humidification( HH) and heta and moisture exchanger( HME) are the most commonly used types of artificial humidification in this situation.In this article, their advantages and disadvantages are itn roduced.HH na d HME are compared in humidification performance,effect no ventilator mechanics and association with venti-lation associated pneumonia.Depending on the clinical scenario, humidifier is reasonably selected, and the selection may changeo ver time according the treatment effect.

BACKGROUND: β-amyloid has been proved to be capable of inducing cell apoptosis and play a vital role in Alzheimer disease (AD).OBJECTIVE: To probe into olanzapine's protective effect and mechanism of PC12 cell apoptosis induced by β-amyloid 25-35.SETTING: Department of Neurology, Southern Building of the General Hospital of Chinese PLA.DESIGN: Randomized design.MATERIALS: This experiment was carried out in the Neuropsychopathic Research Institute, Medical College of the University of Saskatchewan(Canada), between May 2002 and March 2003.METHODS: P12 cells were cultured with RPMI1640 culture medium.100 μL cell suspension was inoculated in each well of 96-well culture plate, and 5 mL suspension was inoculated in 25 cm2 culture bottle covered with collagen and cultured for 24 hours, then with additional 50 μmol/L and 100 μmol/L olanzapine, respectively, for 24 hours, and β-amyloid 25-35 of different concentrations (0.01 μmol/L, 2 μmol/L and 20 μmol/L) for 24 hours. PC12 cell apoptosis was induced by β-amyloid 25-35 in 96-well culture plate and cells were harvested to assay their survival rate with MTF colorimetric assay. PC12 cells in 25-cm2 culture bottles were also harvested to detect the effect of olanzapine on Bax and caspase-3 expression in PC12 cells using Western blot assay.MAIN OUTCOME MEASURES: ① Cell survival rate; ② the expression of Bax and caspase-3 in PC12 cells.RESULTS: ① Cell survival rate: cell activity was found declined from 75% to 35% in PC12 cells induced by β-amyloid 25-35, but obviously increased in PC12 cells due to pretreatment with olanzapine of 50 μmol/L and 100 μmol/L. ② Olanzapine's effects on Bax expression in PC12 cell apoptosis induced by β-amyloid 25-35: Bax expression increased in PC12cells due to exposure to β-amyloid 25-35 of 0.01 μmol/L, 2 μmol/L and 20 μmol/L, but it could be suppressed if pretreated with olanzapine of 50 μmol/L. ③ Effect of olanzapine on caspase-3 expression in PC12apoptotic cells induced by β-amyloid 25-35: There was no change in PC12cells induced by 0.001 μmol/L or 0.01 μmol/L of β-amyloid, as well as in PC12 cells pretreated with 50 μmol/L olanzapine. However, caspase-3 expression obviously increased in PC12 cells exposed to 2 μmol/L and 20 μmol/L of β-amyloid 25-35, and it could be suppressed by pretreatment with 50 μmol/L of olanzapine.CONCLUSION: ① β-amyloid 25-35 can induce the high expression of cell apoptosis related Bax and caspase-3 in vitro cultured PC12 cells. ②Olanzapine can reduce the expression, thus enhancing the survival rate of PC 12 cells.

The neurofilament proteins (NFPs) from different neuronal tissues including Alzheimer and Huntington disease gray matter, rat brain gray, white matter and spinal cord were separated biochemically into two major fractions. A systematic investigation on the distribution, expression and phosphorylation of NFPs in those fractions was undertaken in the present study. It was found that only non-phosphorylated NF-H and NF-M, but not NF-L subunit were detected in Alzheimer brain gray matter high speed supernatant, whereas all neurofilament subunits including non-phosphorylated and phosphorylated were measured in high speed pellet fraction of the same tissue. The hyperphosphorylation of NF-H and NF-M in Alzheimer brain was shown by phosphorylation dependent monoclonal antibodies SMI31 and SMI34. This hyperphosphorylation was confirmed by non-phosphorylation dependent antibody SMI32 with dephosphosphorylation of the samples. Furthermore, an increased amount of NF-H, NH-M and NF-L, detected by SMI33 and NR4 respectively, was also observed in Alzheimer samples, in which the elevation in NF-L was significant. A significantly different immunoblot patterns in distribution, expression and phosphorylation were determined in various position of the neural system and alternative fractions. To our best knowledge, this is the first data shown definite abnormality of NFPs in Alzheimer disease. The information obtained in the present study will be extremely valuable in further study of the proteins both in physiological and pathological conditions.

Background The pollution of agricultural products and the health risks caused by metals have become a hot spot of social concern. As China's main economic agricultural products, peppers are essential for health risk assessment. Objective By exploring the enrichment of common metals in different varieties of peppers in major growing areas of China, a bioavailability-based approach is used to assess dietary health risks of common metals in groups with different characteristics. Methods Through random sampling method, dried pepper samples from major pepper growing areas of China were purchased from the market, and were divided into Hippophae, Capsicum annuum, Magnoliopsida, Capsicum frutescens var, and Capsicum by morphological taxonomy, and a total of 667 batches of peppers were collected. Six common metals arsenic (As), cadmium (Cd), lead (Pb), nickel (Ni), copper (Cu), and zinc (Zn) were evaluated; physiologically based extraction test was designed to estimate the bioavailability of the metals in peppers and their associated dietary health risks were assessed. Results The concentrations of metals Cd and Ni in pepper exceeded the limits of China, and the disqualification rates were 6.1% and 22.7% respectively. The other metals were within the safe range; there were differences in the concentrations of As, Cd, Pb, Cu, and Zn among different pepper varieties (P<0.05). The order of bioavailability of the six metals in pepper from high to low was As (57.9%)>Cd (43.07%)>Zn (42.74%)>Pb (38.04%)>Ni (31.97%)>Cu (31.4%). Based on bioavailability, when the metal concentration in pepper was at the median level, the order of hazard quotient of metals in pepper was Cu>Cd>As>Ni>Zn>Pb, and at the 90th quantile level, the order was Cd>As>Cu>Ni>Zn>Pb; the hazard quotient of single metal element and the total target hazard quotient of combined metal elements were both less than 1, and these indicators of adults were higher than those of children. Conclusion In the collected pepper samples, the non-carcinogenic health risks of single metal elements and multiple metal elements are in the safe range. Based on gastrointestinal bioavailability, the dietary health risk of pepper is further reduced.

Objective: To evaluate the clinical application of Chinese version of Cornell assessment of pediatric delirium (CAPD) scale in children by a pilot study. Methods: A prospective observational study. From June 2017 to December 2017, the original CAPD screen was translated into Chinese and debugged cross-culturally according to the guidelines, which was further applied in the Department of Critical Care Medicine, Children′s Hospital of Chongqing Medical University. The clinical data of 250 patients who were evaluated with the Chinese version of CAPD scale and Richmond agitation-sedation scale were extracted and analyzed with chi-square test or Mann-Whitney U test. Cronbach′s α coefficient,Split-half coefficient and intra-group correlation coefficient were used to evaluate the reliability, while exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to evaluate the structural validity of the scale. The result was compared with the gold standard diagnostic results to evaluate the diagnostic efficacy of the CAPD. Results: Sixty-one (24.4%) patients had delirium during pediatric intensive care unit hospitalization,and significant differences existed between them and 189 patients without delirium in age (χ²=11.220, P=0.011), rates of mechanical ventilation (χ²=6.691, P=0.010) and length of PICU hospitalization (Z=10.656, P=0.001). The Chinese version of the CAPD scale had high discrimination among the 8 items in the main table without skewed distribution and discrete items. The internal and external reliability of the scale were preferable as the Cronbach′s α coefficient was 0.819 and ICC value was 0.835. The KMO value of EFA was 0.834 and Bartlett spherical test showed statistical significance (χ²=661.440, P<0.01). CFA constructed a two-factor structural equation model with favorable fit index:Chi-square/degree of freedom (DF) ratio was 1.786 (χ²=33.930, P=0.019), goodness of fit index (GFI) was 0.967,adjusted GFI was 0.938,root mean square of the approximate error (RMSEA) was 0.056. A good diagnostic efficacy of this scale was demonstrated by receiver operating characteristic curve analysis as when the cut-off was 10, the area under curve was 0.99 (95%CI: 0.97-0.99), sensitivity was 96.7% (95%CI: 88.7-99.6), specificity was 93.1% (95%CI: 88.5-96.3), positive likelihood ratio was 14.0 (95%CI: 13.2-14.9), and the negative likelihood ratio was 0.035 (95%CI: 0.008-0.200). Conclusion The Chinese version of the CAPD Scale has favorable reliability,validity,diagnostic efficacy, as well as feasibility, which should be applied in evaluation of pediatric delirium in clinical observation and research in the future.

OBJECTIVETo observe the effects of electroacupuncture (EA) on the circadian rhythm and suprachiasmatic nucleus (SCN) epigenetic modification in mice with hepatocellular carcinoma (HCC), and to explore the epigenetics mechanism of EA on circadian rhythm in patients with HCC.

METHODSAccording to six zeitbeger time (ZT) of ZT0 (7:00), ZT4 (11:00), ZT8 (15:00), ZT12 (19:00), ZT16 (23:00) and ZT20 (3:00), a total of 108 eligible male C57BL/6J mice were divided into a blank group, a model group and an EA group at each ZT, 6 mice each group. Injection of H22 cancer cell suspension was used to establish the HCC model. After 11 days, EA (2 Hz/15 Hz, 0.2 mA) for 10 days was applied at "Ganshu" (BL 18) and "Zhiyang" (GV 9) in the EA group at each ZT, once a day, 15 min a time; the rats in the blank group and model group were treated with immobilization at the same time and under the same conditions. ClockLab (ACT-500) software was used to record the activity rhythm of mice. After 10 days intervention, MATLAB (R2007b) was used to export the circadian rhythm of mice, and the amplitude and peak phase of the mice were analyzed. The high-throughput epigenetics PCRarray array was applied to detect epigenetics-related gene expression in SCN.

RESULTS(1) After modeling, compared with the blank group, the amplitude of activity was decreased and peak phase was delayed in the model group and EA group at each ZT (all <0.05), but the difference of rhythm parameters between the model group and EA group was not significant (all > 0.05). (2) After intervention, compared with the model group, the amplitude of activity in the EA group at ZT 8 was increased and peak phase was advanced (both <0.05); the difference of the activity amplitude and peak phase between the EA group and model group at ZT0, ZT4, ZT12, ZT16 and ZT20 was not significant (all >0.05); compared with the ZT0, ZT4, ZT12, ZT16 and ZT20, the amplitude of activity in the EA group at ZT 8 was increased and peak phase was advanced (all <0.05). (3) The results of epigenetic PCRarray array showed that after intervention at ZT 8, compared with the blank group, the expression of 48 epigenetic-related genes in SCN of HCC mice was up-regulated; compared with the model group, the relative expression of 49 epigenetic-related genes in the SCN was down-regulated in the EA group; there were 23 epigenetic-related genes differentially expressed among the three groups.

CONCLUSIONEA has benign regulation on circadian rhythm of HCC mice, and achieves the best efficacy at ZT 8. EA at ZT 8 could down-regulate the overexpression of epigenetic-related genes.

OBJECTIVE： To systematically evaluate the effects of roflumilast on lung function of Asian patients with chronic obstructive pulmonary disease （COPD）， and to provide evidence-based reference for rational drug use in the clinic. METHODS： Retrieved from Cochrane library， PubMed， Embase， CBM， CNKI， VIP and Wanfang database， RCTs about roflumilast or roflumilast combined with routine treatment or placebo （trial group） versus routine treatment or placebo （control group） in the treatment of Asian COPD patients were collected. After literature screening， data extraction and quality evaluation with Cochrane bias risk evaluation tool， Meta-analysis was conducted by using Rev Man 5.2 software. RESULTS： Totally 6 RCTs were included， involving 1 494 patients. Meta-analysis showed that pre-bronchodilator FEV1 （pre-FEV1） [MD＝75.19， 95％CI（53.21， 97.17）， P＜0.000 01]， post-bronchodilator FEV1 （post-FEV1） [MD＝56.60， 95％CI（27.56， 85.63）， P＝0.000 1]， forced vital capacity （FVC） [MD＝43.67， 95％CI （15.91，71.43）， P＝0.002]， average flow rate of post-bronchodilator 25％-75％ of forced vital capacity （post-FEF25％-75％） [MD＝14.58， 95％CI （8.43， 20.73）， P＜0.001]， the incidence of diarrhea [RR＝5.06， 95％CI （1.26，20.27）， P＝0.02]， respiratory infection [RR＝1.94， 95％CI （1.30，2.90）， P＝0.001]， decreased appetite [RR＝7.43， 95％CI （2.94，18.79）， P＝0.001]， body weight decrease [RR＝5.46， 95％CI （2.12，14.03）， P＝0.001]， headache [RR＝7.73， 95％CI （1.42，42.16）， P＝0.02]， dizziness [RR＝3.44， 95％CI （1.28，9.27）， P＝0.01]， gastritis [RR＝5.09， 95％CI （1.49， 17.45）， P＝0.01] and anorexia [RR＝5.06， 95％CI （1.97， 13.00）， P＝0.001] in trial group were significantly higher than control group； St. George’s Respiratory Questionnaire （SGRQ） total score [MD＝－5.82， 95％CI（－7.77， －3.87）， P＜0.001]， respiratory symptom score [MD＝－1.67， 95％CI （－2.51，  －0.84）， P＜0.001]， activity limited score [MD＝－1.55，   95％CI （－2.14， －0.97）， P＜0.001] and disease impact score [MD＝－2.59， 95％CI （－3.40，－1.79）， P＜0.001] of trial group were significantly lower than those of control group. CONCLUSIONS： Roflumilast can improve lung function and dyspnea in Asian COPD patients， but it can increase the risk of ADR.