Chop and Grp78 genes are key genes in endoplasmic reticulum stress(ERS).To explore the gene alteration of Chop and Grp78 in embryo with spina bifida,we studied Chop and Grp78 gene expression by qRT-PCR in neural tube of rat with spina bifida in E12 and primary cultured neuroepithelial stem cells(NEP).We found higher expression of both Chop and Grp78 in neural tube of rat with spina bifida than normal rats.While Chop and Grp78 genes were up-regulated after NEP differentiated into neuron.The up-regulation of Chop and Grp78 genes in neural rube of rat and NEP might be involved in the abnormal apoptosis in spina bifida related with ERS.And we found the primary culture of NEP provided a good model for embryo early development research.

OBJECTIVETo explore the distribution features of Chinese medical constitutions in different ages population, thus providing scientific evidence of constitution process theory.

METHODSRecruited were 21 948 cases from a survey of Chinese medical constitutions and health conditions in 9 provinces or municipalities across China (including Jiangsu, Anhui, Gansu, Qinghai, Fujian, Beijing, Jilin, Jiangxi, and Henan) from Dec 2005 to Jan 2007. The body constitution type of individual was diagnosed using discriminant analysis on the basis of Chinese medical constitution questionnaire. By using correspondence analysis, the correlation between the general population, genders, ages, and Chinese medical constitution types was studied.

RESULTSConstitutions of yin-deficiency type, wetness-heat type, qi-depression type, and special diathesis type often occurred in the population ranging 15 -24 years old. Gentleness type mostly occurred in the population ranging 25 -44 years old. During this time period, phlegm-wetness type and wetness-heat type were liable to occur in males, while blood-stasis type was liable to occur in females. Qi-deficiency type and yang-deficiency type were most often seen in those older than 45 years. Phlegm-wetness type and blood-stasis type body constitution were also liable to occur in those older than 45 years.

CONCLUSIONSThe distribution features were different in different Chinese medical constitutions. Different constitution types exist in different genders. Different constitution types exist different ages population.

Asian Continental Ancestry Group ; Body Constitution ; China ; Discriminant Analysis ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Qi ; Surveys and Questionnaires ; Yang Deficiency ; Yin Deficiency

A chiral high-performance liquid chromatography method was developed for the simultaneous determination of ibuprofen enantiomers in dog plasma. It was used to study the pharmacokinetics in the Beagle dog after intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen. Ketoprofen was chosen as the internal standard. After a simple precipitation using methanol as the precipitating solvent, both analytes and IS were separated on a Kromasil 100-5CHI-TBB chiral column (250 mm x4.6 mm, 5 μm) with isocratic elution using acetonitrile - 20 mmol x L(-1) phosphate buffer (pH 3.0, containing 5% methanol) (6 : 4) as the mobile phase. The detection wavelength was 220 nm. Liner calibration curves for both of the ibuprofen enantiomers were over the concentration range from 0.5 to 50 μg x mL(-1) with a lower limit of quantification of 0.5 μg x mL(-1), the accuracies were all in standard ranges. The intra- and inter- assay precisions were all below 7%. The recovery rate was 93.1% to 100.4%. The experiments proved that the method was simple, rapid and sensitive. It can be used in the quantitative determination of ibuprofen enantiomers in dog plasma. The method was used to determine the concentration of ibuprofen enantiomers in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen (9 mg x kg(-1)) and the pharmacokinetics parameters were calculated based on the concentration-time curves. The C(max) of S-ibuprofen in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen were 30.8 ± 4.7, 46.1 ± 5.9 and 20.0 ± 2.6 μg x mL(-1), respectively. In terms of the exposure of active ingredient, it revealed a significant difference between the administration of S-ibuprofen and the other two groups. The systematical R- to S- chiral inversion was discussed. Comparing the pharmacokinetic parameters at different doses, chiral inversion were 70.1% ± 36.6% and 76.4% ± 36.2%, respectively, after intravenous administration of racemic- and R-ibuprofen. This study provides a theoretical basis for the safety of ibuprofen formula of injection drug.

Objective: To evaluate the value of clinical application of Heart of the City type TJH-03A remote electrocardiogram recorder (remote ECG). Methods: A total of 1 014 community residents from Wuhan received ECG examination by Heart of the City type TJH-03A remote ECG recorder. Clinical and ECG data of all subjects were collected and analyzed. Results: There were 359 (35.40%) cases with normal ECG and 655 (64.60%) cases with abnormal ECG, after remote ECG examination . There were 581 cases had a variety of arrhythmia in 655 cases with abnormal ECG, so there were 828 cases times with abnormal ECG, in which there were （1）320 cases times (38.65%) with repolarization abnormality,（2）98 cases times(11.84%) with sinus bradycardia, （3）98 cases times (11.84%)with myocardial ischemia,（4）78 cases times (9.42%)with conduction block,（5）56 cases times(6.76%) with ventricular hypertrophy and high voltage,（6）43 cases times(5.19%) with atrial premature beats（7）37 cases times (4.47%)with atrial fibrillation,（8）35 cases times (4.23%)with sinus tachycardia,（9）24 cases times (2.90%)with ventricular premature beats, （10）19 cases times (2.29%)with suspected myocardial infarction according to ECG abnormality rate order. In addition, there were 5 cases times with QT interval prolongation, and abnormal ECG with abnormality rate ≤3 cases times: atrial tachycardia, atrial flutter, supraventricular tachycardia, ventricular tachycardia, Brugada wave, dextrocardia. Conclusion: Heart of the City type TJH-03A remote electrocardiogram recorder is convenient to use, it can perform remote electrocardiogram record, and find a variety of arrhythmias. It’s important for ECG diagnosis, especially for diagnosis of arrhythmias.

The immune system is a complex system involving multiple organs,and it is vulnerable to age,gender,environment and other factors.For a variation normal physiological range,it is a great challenge to evaluate drug-induced immunotoxicity in preclinical safety study.Histomorphologic assessment of the immune system is a recognized cornerstone in the identification of immunotoxicity at present.In this paper,the principles of pathological evaluation for immune system,and pathological evaluation for important immune organs including thymus,spleen,lymph nodes are discussed briefly,so that it is intended to assist toxicity pathologists in the accurate and consistent characterization of intended and unintended drug-induced alterations of the immune system.

Objective To investigate the effect of Tetramethylpyrazine (extracted from Chinese herbal medicine Ligusticum wallichii) employed in the early stage of severe brain injury on the restoration of brain function in coma patients monitored with digitized cerebral state monitor and clinical signs.Methods A total of 364 patients were referred to us from Emergency Department and Neurosurgery Department,Shenzhen People's Hospital from January 2006 through May 2012.The scores of patients'GlasgowPittsburgh coma scales were between 7-20 as brain injury happened within 24 h and survived more than two weeks.All patients were randomly (random number) divided into two groups:Tetramethylpyrazine group (n =186) and control group (n =178).The patients of control group received routine treatment,and the patients of Tetramethylpyrazine group were treated with Tetramethylpyrazine in addition to routine treatment in early stage.The patients of two groups were assessed with cerebral state indexes (CSI) and GlasgowPittsburgh coma scales before treatment and 3,7,14 days after treatment.Statistical comparisons between groups were analyzed by using repeated measure design analysis of variance.Results A repeated measures design analysis of variance indicated that the CSI and clinical signs (Glasgow-Pittsburgh coma scale) were improved significantly in Tetramethylpyrazine group than those in the control group at 3,7,14 days after treatment (P =0.024).Conclusions Tetramethylpyrazine can protect brain function and improve clinical signs in patients with severe brain injury in the early stage.

Objective To evaluate the accuracy of the transcutaneous bilirubin (TcB) at different sites including the chest (covered and uncovered),forehead and scapula,compared with total serum bilirubin (TSB) before and after phototherapy.Method Neonates who underwent blood test of TSB together with the average TcB at chest over 6 mg/dl from September 2015 to July 2016 in our Hospital were enrolled in our study.TcB measurements were done by the transcutaneous bilirubinometer (JH20-1 C) at the sites of the chest,forehead and scapula within 30 minutes after venous or arterious blood sampling for testing TSB after admission.An area of 2 cm diameter over the left chest was covered during phototherpy.TSB was tested immediately and within 12 ～ 24 hours after phototherapy,while TcB was measured within 0.5 hour after blood sampling at the covered sites over the left chest,right chest,forehead and scapula.IBM SPSS 20.0 software was used for data analysis.Data were compared via Pearson correlation analysis,ANOVA of repeated measurement data,student's t test and Bland-Altman analysis.Result A total of 437 data were collected from 364 neonates were enrolled in our study.Before phototherapy,the values of TcB at different sites were highly correlated and consistent with TSB (P ＜ 0.05),especially taken from the chest (the difference value of TcB and TSB-1.2 ± 2.3 mg/dl).Immediately and within 12 ～ 24 hours after the phototherapy,the values of TSB and TcB taken from the covered left chest showed the highest consistency (-1.2±2.3 mg/dl and-0.5 ± 1.6 mg/dl).When TSB exceeded 15 mg/dl before phototherapy,the difference between TSB and TcB taken from chest was 1.5 ± 1.6 mg/dl,while if TSB was below 15 mg/dl,the difference was-1.9 ± 1.9 mg/dl.They were significantly different (P ＜ 0.001).And difference between TSB and TcB taken from chest was not affected by gender gestational age,birth weight,days of birth and different measurements.When TcB taken from the covered or uncovered chest was less than the TSB threshold value of 3.3 mg/dl for phototherapyl,or the TcB of the left covered sternum lower than the threshold value of 2.6 mg/ml for cessation of phototherapy,97.5％ of the TSB would not exceed the corresponding value.Conclusion The TcB values of both uncovered chest before phototherapy and covered chest after phototherapy were highly consistent with TSB,and could be applied in the replacement of TSB in the assessment and management of neonatal jaundice.

Objective To study the effect of three different modes of non-invasive positive pressure ventilation on cardiac indices of premature infants with respiratory distress syndrome (RDS).Method From January 2014 to October 2015,preterm infants who had RDS received intubation-pulmonary surfactantextubation in the neonatal intensive care unit of the Hospital were randomly assigned (by random number table) to three groups based on the primary mode of ventilation:nasal continuous positive airway pressure (NCPAP),bi-level positive airway pressure (BiPAP),and synchronized bi-level positive airway pressure (SBiPAP).The mean airway pressure (MAP) were about 6 cmH2O in the three groups.The level of plasma B-type natriuretic peptide (BNP),cardiac troponin Ⅰ (cTnI),and correct QT intervals dispersion (QTcd) were monitored before and 42-54 h after non-invasive ventilation.Result There were 173 cases in our study,59 of which in NCPAP group,56 in BiPAP group,and 58 in SBiPAP group.The plasma BNP level at 42-54 h after non-invasive ventilation in the three groups were all higher than that before non-invasive ventilation [NCPAP group:(247.9 ± 137.9) ng/L vs.(182.5 ± 1 10.7) ng/L,P =0.007;BiPAP group:(258.5 ± 131.2) ng/L vs.(182.6 ± 105.0) ng/L,P ＜ 0.001;and SBiPAP group:(260.9 ± 159.7) ng/L vs.(177.5 ± 101.5) ng/L,P =0.002].After 42-54 h non-invasive ventilation,there were no significant changes of plasma cTnI level and QTcd in all the three groups (all P ＞ 0.05).The level of plasma BNP,cTnI,and QTcd among the three groups before and after 42-54 h non-invasive ventilation all showed no significant differences statistically (all P ＞ 0.05).Conclusion Longer duration (42-54 h) of non-invasive positive pressure ventilation (MAP:6 cmH2O) in preterm infants with RDS may lead to increased plasma BNP level,and may affect their cardiac function.However,it may not lead to serious myocardial damage and abnormality of ventricular repolarization.There were no significant differences in cardiac indices of premature infant with RDS among NCPAP,BiPAP,and SBiPAP group with the same MAP.

A chiral high-performance liquid chromatography method was developed for the simultaneous determination of ibuprofen enantiomers in dog plasma. It was used to study the pharmacokinetics in the Beagle dog after intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen. Ketoprofen was chosen as the internal standard. After a simple precipitation using methanol as the precipitating solvent, both analytes and IS were separated on a Kromasil 100-5CHI-TBB chiral column (250 mm x4.6 mm, 5 μm) with isocratic elution using acetonitrile - 20 mmol x L(-1) phosphate buffer (pH 3.0, containing 5% methanol) (6 : 4) as the mobile phase. The detection wavelength was 220 nm. Liner calibration curves for both of the ibuprofen enantiomers were over the concentration range from 0.5 to 50 μg x mL(-1) with a lower limit of quantification of 0.5 μg x mL(-1), the accuracies were all in standard ranges. The intra- and inter- assay precisions were all below 7%. The recovery rate was 93.1% to 100.4%. The experiments proved that the method was simple, rapid and sensitive. It can be used in the quantitative determination of ibuprofen enantiomers in dog plasma. The method was used to determine the concentration of ibuprofen enantiomers in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen (9 mg x kg(-1)) and the pharmacokinetics parameters were calculated based on the concentration-time curves. The C(max) of S-ibuprofen in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen were 30.8 ± 4.7, 46.1 ± 5.9 and 20.0 ± 2.6 μg x mL(-1), respectively. In terms of the exposure of active ingredient, it revealed a significant difference between the administration of S-ibuprofen and the other two groups. The systematical R- to S- chiral inversion was discussed. Comparing the pharmacokinetic parameters at different doses, chiral inversion were 70.1% ± 36.6% and 76.4% ± 36.2%, respectively, after intravenous administration of racemic- and R-ibuprofen. This study provides a theoretical basis for the safety of ibuprofen formula of injection drug.
Animals ; Chromatography, High Pressure Liquid ; Dogs ; Ibuprofen ; blood ; pharmacokinetics ; Stereoisomerism

AIM: To investigate the expression of microRNA-375 (miR-375) in hepatocellular carcinoma (HCC) and to analyze the target genes and signaling pathways regulated by miR-375.METHODS: The expression of miR-375 was examined at tissue microarray of HCC by in situ hybridization.The whole human genome chip and bioinforma-tics analysis were applied to screen out the differential expression genes and signaling pathways in 4 HCC cell lines trans-fected with miR-375 mimic.RESULTS:In situ hybridization showed the expression of miR-375 in HCC tissues were obvi-ously higher than that in tumor-adjacent tissues (P<0.05).There were 20 co-upregulated genes and 17 co-downregulated genes in all 4 cell lines.Bioinformatic analysis showed that there were 54 signaling pathways related to up-regulated genes and 48 signaling pathways related to down-regulated genes in all 4 cell lines.CONCLUSION: miR-375 may play a key role in the pathological process of HCC.The bioinformatic analysis is able to screen the target genes and signaling pathways regulated by miR-375 and to provide an explicit direction for further mechanism research on HCC.