Objective: To observe the induced effect of low dose of tunicamycin on endoplasmic reticulum stress (ERS) of A549 human lung adenocarcinoma cells in vitro and the change of Bcl-2 associated athanogene 1 (BAG-1) protein expression, as well as the changes of cisplatin (DDP) sensitivity and the BAG-1 protein expression. Methods: The expressions of GRP78 (a marker protein in ERS) and BAG-1 proteins in A549 cells treated with low dose of tunicamycin were detected by Western blotting. The change of half inhibitory concentration (IC50) of DDP for A549 cells after pretreatment with tunicamycin was measured by MTT method, and the DDP sensitivity was determined by flow cytometry (FCM). The Western blotting was carried out to detect the expressions of BAG-1 and procaspase-12 proteins in A549 cells induced by DDP after pretreatment with tunicamycin. Results: The ERS in A549 cells could be induced by pretreatment with 1.25 μg/mL tunicamycin for 8 h, which displayed that the expression levels of GRP78 and BAG-1 proteins were both up-regulated (P <0.05). The ERS could increase the DDP sensitivity in the A549 cells (P <0.05). Before ERS occurred, all of three doses of DDP (1.25, 2.5 and 5 μg/mL) could up-regulate the expression level of BAG-1 protein (P <0.05), and this effect was more obvious in 1.25 μg/mL DDP-treated A549 cells. When ERS occurred, the expression levels of BAG-1 protein in all of three doses of DDP (1.25, 2.5 and 5 μg/mL)-treated A549 cells were down-regulated in a dosedependent manner as compared with that in the A549 cells without DDP treatment (P <0.05). The DDP dose of 2.5 and 5 μg/mL could induce apoptosis by ERS pathway, and the expression levels of BAG-1 and procaspase-12 proteins were both down-regulated during this process (P <0.05). Conclusion: BAG-1 may be one of the important regulatory factors in both pathways of ERS- and cisplatin-induced apoptosis of lung cancer cells, and ERS-related apoptotic pathway may be one of the important pathways of cisplatininduced apoptosis of lung cancer cells. Copyright © 2012 by TUMOR.

AIM: To observe the effects of Dispel Stasis Decoction(Radix et Rhizowa Salviae multiorrhizae,Rhizoma Sparganii,Rhizoma Curcumae,etc) on TNF-? and E_2 in rats with endometriosis(EMS),and to observe its anti-inflammatory and analgesic effect. METHODS: Endometriosis rat models were made by autograft of endometrium in abdomen.Four weeks after operation,EMS model rats were randomly divided into 5 groups: a model group,3 Dispel Stasis Decoction groups and a danazol group.All the rats were treated for three weeks respectively,and then anaesthetised and killed.The ectopic endometrium's focuses were observed by microscope,the levels of TNF-? and E_2 in the serum of all groups were measured by radioimmunoassay.The method of body twist and ear edema of mouse were used to the analysis the anti-inflammatory and analgesic effect of Dispel Stasis Decoction. RESULTS: The survived graft shrinked and the number of the glanduls decreased in rats of Dispel Stasis Decoction group.The levels of TNF-? and E_2 in the serum were significantly lower than that of the model group.Also,Dispel Stasis Decoction could inhibite the ear edema of the mouse induced by dimethylbenzene and the body twist of the mouse caused by acetic acid notablely. CONCLUSION: Dispel Stasis Decoction inhibited growth of the graft and showed a significant therapeutic effects on EMS model rat.It also has notable functions of anti-inflammatory and analgesic.This may be related to its inhibition of TNF-? and E_2 levels.

Objective To observe the effect of Sijunzi Decoction(SD) and Huangqi Sijunzi Decoction(HSD) on mitochondrial succinate dehydrogenase,cytochrome oxidase activity of liver in rats with spleen asthenia,thus to reveal the pathogenesis mechanism of spleen asthenia from energy metabolism,and to clarify the therapeutic mechanism of spleen-invigorating and Qi-tonifying herbs.Methods Forty SD rats were randomly divided into 4 groups:normal control group,spleen-asthenia model group,SD(10.5 g/kg) group and HSD(18 g/kg) group,10 rats in each group.Except that the normal control group,the rats in the other groups were fed with half-full diet once every other day and with gastic gavage of Xiaochengqi Decoction 60 g/kg every day to establish animal model of spleen asthenia.After 15 days,the model rats were administered the corresponding drugs according to the experimental design for 4 continuous weeks.The changes of mitochondrial succinate dehydrogenase,cytochrome oxidase activity of liver were measured,and the general status of the rats were observed.Results Compared with the normal control group,the level of mitochondrial succinate dehydrogenase and cytochrome oxidase activity in liver of spleen asthenia group were decreased obviously(P

BACKGROUND: Perinatal hypoxic-ischemic encephalopathy(HIE) is the primary cause of neonatal brain injury, which retards the mental development in affected infants.OBJECTIVE: To investigate the influence of early intervention on mental and psychological development in infants with HIE, study the time-effect relation of the early intervention, and to find an optimal time for intervention.DESIGN: A time series of following-up and a non-randomized concurrent controlled investigation.SETTING: Xiangya Hospital and Xiangya School of Medicine Affiliated to Central South University.PARTICIPANTS: From February 1999 to May 2001, in the Pediatric Department of Xiangya Hospital Affiliated to the Central South University, the inpatient and outpatient infants with HIE were selected. There were 32 inpatients in the intervention group, 10 with moderate HIE and 22 with severe HIE. There were 36 outpatients in the control group, 10 with moderate HIE and 26 with severe HIE. Comparison was performed between these two groups.METHODS: BRS and the Infant and Child Mental Development Scales,made by The Institute of Psychology of The Chinese Academy of Science and The China National Children' s Center(CNCC), were adopted in the assessment between the two groups.MAIN OUTCOME MEASURES: Mental Development Index(MDI) and Psychomotor Development Index(PDI) scores of the two groups were compared.were significantly higher in the intervention group(90.50 ± 11.12/90. 34±12.49,94.06±14.96/92.03±13.07,90.78±7.46/91.38 ± 13.87)than those in the control group(62.28±7.44/62.67±6.06, 59.11following-up results showed that one patient in the intervention group had a MDI score at the critical threshold value, and two patients had PDI scores at the critical threshold value. For all the other patients in this group, the MDI/PDI scores of them were above the moderate range. In contrast, all the 36 infants in control group had developed mental deficiencies at that time.CONCLUSION: A quantifiable effect of the intervention can be observed in patients at 3 months of life. This indicates that an early intervention is essential for improving the mental development in infants with HIE.

Objective To investigate the expression of Notch4 protein and to analyze its correlation with the clinical parameters and the microvessel dentisty in renal cell carcinoma. Methods The expression of Notch4 was examined in 60 cases of renal cell carcinoma and the para-carcinoma tissue by SP immunohistochemical stain-ing ,and CD34 detection was used for counting microvessel density. Statistical analysis was performed to reveal the correlation with clinicopathological parameters ,microvessel density and prognosis. Results The positive rate of Notch4 protein expression was 75%(45/60)in para-carcinoma tissue,and was 43.3%(26/60)in renal cell car-cinoma,with significant difference on tumor grade and Lymph node metastasis(P<0.05). The microvessel densi-ty in Notch4 positive tissues was significant lower than that in the negative samples(P<0.05). The survival time of patients with Notch4 positive expression was significantly longer than that of patients with Notch4 negative expres-sion(P<0.05). Conclusion Notch4 protein plays an important role in the development of renal cell carcinoma. Notch4 expression might both attenuate the malignant biological characteristics and suppress the angiogenesis dur-ing tumor development.

Objective To study absorption characteristic of dioscin from Dioscorea nipponica Makino extract in rat intestine.Methods Single-pass intestinal perfusion (SPIP) model was used for rat in situ and HPLC was used to determine the concentrations of dioscin.The effects of different intestinal segments,drug concentration and P-glycoprotein (P-gp) inhibitor on intestinal absorption were investigated.Results Dioscin could be absorbed in the whole intestine,the absorption rate constant (Ka) and the apparent coefficient (Papp) of dioscin decreased following the sequence of ileum > duodenum =jejunum > colon.Absorption parameters of dioscin had no significant difference at different concentrations (40,80,120 mg·L-1).There were significant differences in Ka and Papp values between P-gp inhibitor group and no P-gp inhibitor group(P<0.05).Conclusion The saturate phenomena was not observed under the test range of drug concentration,and the absorption mechanism may be passive diffusion transport.Dioscin in Dioscorea nipponica Makino extract may be the substrate of P-gp.

To study the effect of antioxidants R-(+)-lipoic acid (R-LA) on cells growth,proliferation and related mechanisms in human HepG2 cells lines.MTT was used to measure cells growth and proliferation.Reactive oxygen species (ROS) kit was used to analyze ROS level.Cell apoptosis and cell morphological changes were observed by flow cytometry and Hoechst 33258 test.Protein expression levels of apoptosis,autophagy and related pathway were analyzed through Western blot,including Bax,Bcl-2,caspase 3,PARP,ATG5,ATG7,LC3,Beclin1,mTOR,P70S6K,P38,P53,ERK and Akt etc.Results showed that cell growth and proliferation were inhibited in a dose-and time-dependent manner after being treated by lipoic acid.R-LA could increase ROS production,pro-apoptosis proteins Bax levels,activated caspase family and PARP.Meanwhile,R-LA could up-regulate the levels of autophagy-related proteins including ATG5,ATG7,Beclin1 and LC3,and down-regulate phosphomTOR and P70S6K levels.Signal pathway results showed that R-LA could up-regulate phospho-P38 and phospho-JNK levels,and decrease phospho-Akt and phospho-ERK.When adding 3-methyladenine,autophagy was inhibited.Thus,R-LA might activate autophagy and induce apoptosis by P38/AMPK-JNK,PI3K/AKT and Ras/ Raf/MEK/ERK pathways.

Objective To investigate the effects of dexmedetomidine on postoperative cognitive dysfunction (POCD) in patients with obstructive sleep apnea. Methods A total of 50 patients with obstructive sleep apnea were divided into 2 groups: a dexmedetomidine group and a control group. Dexmedetomidine and 0.9% saline solution were given before and during the operation in the dexmedetomidine group and the control group respectively. MMSE scores were estimated at different time, and the concentration of serum S100β and NSE were detected before anesthesia at 3 h, 6 h, 24 h and 48 h after operation. Results One day after surgery, MMES score decreased significantly in both groups,of which MMES was notably higher in the DEX group than that in the control group (P<0.05). In both groups, S100βand NSE levels were significantly higher at T2, T3 and T4 than those at T1, and were the highest at T3 (P<0.05). S100β and NSE levels were significantly lower in the DEX group than those in the control group (P<0.05). Conclusion Dexmedetomidine can reduce the incidence of POCD in patients with obstructive sleep apnea. Its mechanism may relate to neuroprotection.

Objective: To educate the high-quality nurses with ability and to improve their capability in holistic nursing.Methods: Interlocution of nursing case is applied to theory teaching.Clinic probation and simulative act are applied to practical teaching.Results:Situational teaching method is welcome among the experimental students whose grade is higher than that of the students of contrast class.Conclusion: It is propitious to education in synthesis ability of students to use situational teaching method based on the holistic nursing.

OBJECTIVE:To synthesize the aryl-pyridazinone acid and curcumin ester. METHODS:With the raw material of 5-methyl-2-(3-chloro-4-fluorophenyl)-2-oxo-pyridazine acid (compound 1) and curcumin,there was ester-forming in the two sides of a phenolic hydroxyl and pyridazin-6-one carboxyl in curcumin by the catalysis of N,N-dicyclohexyl carbodiimide(DCC)/4- dimethylaminopyridine (DMAP). The targeted product,MS and NMR characterization of the structure were obtained through column chromatographic separation. Single factor was adopted to detect the effect of mixture ratio of curcumin and compound 1,re-action temperature and time and catalyst on the reactions. RESULTS:The productivity of targeted product (aryl-pyridazinone acid and curcumin ester)was 56.3%(in curcumin),the content by HPLC was 98.1%. The optimum conditions were as follows as the mixture ratio of curcumin and compound 1 was 1∶3,reaction temperature was 50 ℃,reaction time was 10 h and the catalyst was DCC/DMAP. CONCLUSIONS:The aryl-pyridazinone acid and curcumin ester is successfully synthesized with stable process.