Objective To investigate the alteration of phosphorylated GluR1Ser831 and behavioural effects in a rat model of levodopa-induced motor complications after Ca2 +/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) inhibitor KN-93 treatment. Methods The hemi-parkinsonian rat model was produced by injecting stereotaxically 6-OHDA to right medial forebrain bundle. Then, rats were intraperitoneally treated with levodopa ( 50 mg/kg with benserazide 12.5 mg/kg,twice daily) for 22 days. On day 23 ,rats received KN-93 before levodopa administration. Rotational duration was estimated. After sacrificed, subcellualr distribution of GluR1 and phosphorylated GluR1Ser831 were observed by western blot. Results The study showed that CaMKⅡ inhibitor KN-93 prolonged rotational duration. Moreover, KN-93 could regulate subcellular distribution of GluR1 and reduce hyperphosphorylation of GluR1 Ser831, which was closely associated with levodopa-induced motor complications. The expression of membrane GluR1 and phosphorylated GluR1Ser831 was (83.4 ±4.2)% and (47.2 ±5.2)% ,respectively. Conclusions These results indicated that activation of CaMKⅡ contributed to development of motor complications, through a mechanism that involved an increase in phosphorylated GluR1 Ser831. Pharmaceuticals which act to inhibit CaMKⅡ may be useful in the treatment of the motor complications in parkinsonian patients.

Objective To observe the effect of penetrating electro-acupuncture at scalp-acupoints on the motor function and oxidative stress action of mice with Parkinson's disease (PD).Methods Mouse model of PD was established by 5-day intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP,30 mg/kg),and then PD mice were given electro-acupuncture set at different parameters.The effect of the electroacupuncture on the behavior and expression of tyrosine hydroxylase (TH) of mice were observed to screen out the appropriate treatment parameters.Healthy C57BL/6 mice were randomly divided into blank group,model group,positive group (madopar,6.25 mg/kg) and electro-acupuncture group.The mice except for blank group were given intraperitoneal injection of MPTP to induce PD,and then the PD mice of positive group and electroacupuncture group were treated with madopar(6.25 mg/kg) and electro-acupuncture respectively from the 6th day for 7 continuous days.Behavioral test was carried out on the 5~ modeling day and on the Th electro-acupuncture treatment day to evaluate the motor function of the mice.After the mice were killed and their brains were isolated,mitochondrial complex Ⅰ ～Ⅳ activities,reactive oxygen species(ROS) level,malondialdehyde (MDA) content,and total activities of superoxide dismutase (SOD) in the cerebral mitochondria were determined to evaluate the effect of electro-acupuncture at acupoints on anti-oxidative stress of PD mice.Results The motor function of PD mice was improved,the activity of mitochondrial complex Ⅰ was increased,the contents of ROS and MDA in cerebral mitochondria were decreased,and the activity of SOD was increased in the electro-acupuncture group,the differences being significant compared with those of the model group (P ＜ 0.05 or P ＜ 0.01).Conclusion Penetrating electro-acupuncture at scalp-acupoints can increase the anti-oxidative ability of the cerebral mitochondria and improve the motor function of PD mice.

Abstract:Objective - ToinvestigatetheeffectofchrysotileasbestosongeneexpressioninhumanbronchialepithelialBEAS 2B Methods - cells. BEAS 2B cells were randomly divided into two groups. The cells in the chrysotile malignant transformation- groupweretreatedwith 20μg/cm²chrysotiletoestablishthechrysotileinducedmalignanttransformationBEAS 2Bcellmodel, andthecellsinthecontrolgroupweretreatedwiththesamevolumeofphosphatesaltbuffersolution.ThetotalRNAinthecells--wasextractedandthecDNAwassynthesizedbyreversetranscription.Cy5dCTPandCy3dCTPfluoresceinwereusedtolabel the two groups to prepare probes for chip scanning. LuxScan 3.0 image analysis software was used to analyze the fluorescence signal of labeled DNA, and the differentially expressed genes were screened. The Kyoto Encyclopedia of Genes and Genomes Results (KEGG) signaling pathway analysis and Gene Ontology (GO) enrichment analysis were carried out. There were 642 - - differentiallyexpressedgenes(193up regulatedand449down regulated)inchrysotilemalignanttransformationgroupcompared with the control group. The KEGG signaling pathway analysis and GO enrichment analysis showed that the differentially - expressed genes in the malignant transformed BEAS 2B cells induced by chrysotile asbestos were mainly involved in P53 - signaling pathway, histone H3 K9 methylation and methylenetetrahydrofolate reductase deficiency pathway, phosphoinositide binding protein 3 activated protein kinase B signaling pathway, nucleoside phosphate metabolism process and the expression Conclusion inhibitionofhistocompatibilitycomplexⅡantigenpresentation. Chrysotileasbestoscaninducethechangeofgene - - expression profile in BEAS 2B cells. The P53 signaling pathway, histone H3 K9 methylation and other related pathways are

BACKGROUND: Because of complicated physiological environment and difficulty to control experimental conditions, it is difficult to get satisfactory results from in vivo studies of cell mechanics.OBJECTIVE: To study the action and mechanism of p38MAPK signaling pathways on myoblast apoptosis based on successful construction of in vitro mechanical stimulation models.METHODS: The C2C12 cells cultured in vitro were divided into control group and SB203580 treatment group. Cyclic tensile stress was applied on the C2C12 myoblast cells for 0, 6, 12 and 24 hours in each group. The Flexcell Strain Unit-5000T was used to expose C2C12 myoblast cell to an equiaxial cyclic of 15% magnitude and a frequency of 10 cycles/min, each cycle including the 3 s stretch and 3 s relaxation. Hoechst 33258 fluorescent staining and optical microscope were used to detect cell apoptosis. RT-PCR, flow cytometric analysis were used to observe the apoptosis of C2C12 myoblast cells and Western blotting were used to detect the activity of p38MAPK and p-p38MAPK. RESULTS AND CONCLUSION: The optical microscope tested the change in the morphology. Hoechst 33258 staining showed that after treatment with cyclic stress, the cell took the typical appearance of apoptosis with chromatin condensation and apoptotic bodies. RT-PCR and flow cytometry showed that with the extension of time the rate of the apoptosis of C2C12 myoblast cell increased. And cells imposed SB203580 before imposing cyclical tensile stress, the results showed that the apoptosis was markedly affected, and the p-p38MAPK expression declined apparently. These findings demonstrate that p38MAPK signaling pathways in stress mediated into C2C12 myoblast cell apoptosis plays an important role.

Objective: To evaluate the feeding effect of not monitoring gastric residual volume in ICU patients receiving continuous enteral feeding,including complications and calorie intake. Methods: We searched for relevant studies in China national knowledge internet(CNKI), Wanfang Data, PubMed, Embase, Cochrane library. We included all Randomized controlled trials (RCTs) and pre-post studies related to the feeding effect of not monitoring gastric residual volume in ICU patients receiving continuous enteral feeding. Two researchers independently screened, appraised and extracted data, and meta-analysis was conducted via RevMan 5.3 software. Results: 3 RCTs and 2 pre-post studies with 1 000 patients were included. Not monitoring gastric residual volume increase the rate of vomiting [OR=1.35, 95%CI(1.02, 1.80), Z=2.08, P=0.04], decrease the proportion of intolerance to enteral nutrition [OR=0.35, 95%CI(0.26, 0.46), Z=7.29, P<0.01], there were no significant differences in diarrhea [OR=1.14, 95%CI(0.78, 1.67), Z=0.67, P=0.51] and distention[OR=1.24, 95%CI(0.76, 2.03), Z=0.87, P=0.38]. The cumulative calorie deficit between targeted volume and provided volume in not monitoring gastric residual volume group was significantly lower than the control group[MD=-0.29, 95%CI(-0.47, -0.11), Z=3.23, P=0.001], daily provided calorie amount was also significantly higher than the control group [MD=0.35, 95%CI(0.10, 0.59), Z=2.75, P=0.006]. Conclusions Not monitoring gastric residual volume in ICU patients increase calorie intake and have better enteral nutrition provision, decrease the proportion of intolerance to enteral nutrition. Monitoring gastric residual volume should not be taken as a routine task in critical care nursing.

OBJECTIVETo evaluate the expression of FBXW7 in esophageal squamous cell carcinoma (ESCC) and to explore the correlation of FBXW7 expression with clinicopathologic features and prognosis of ESCC.

METHODSNinety cases of ESCC and twenty cases of tumor-adjacent normal tissues and forty intraepithelial neoplasia tissues were detected by immunohistochemistry methods. The expression of FBXW7 in 40 surgical ESCC tissues and tumor-adjacent normal tissues was detected by Western blotting and RT-PCR. The relationship between the expression of FBXW7, clinicopathological characteristics and prognosis was analyzed.

RESULTSThe positive rate of FBXW7 protein was significantly lower in the ESCC and high-grade intraepithelial neoplasia tissues than in the tumor-adjacent normal tissues and low grade intraepithelial neoplasia tissues (40.0% and 33.3% vs. 85.0% and 77.3%, χ² = 21.923, P < 0.001). The FBXW7 protein was down-regulated in ESCC tissues (P < 0.05), whereas the FBXW7 mRNA was down-regulated in ESCC tissues compared with that in the paracancerous tissues. The expression of FBXW7 was significantly correlated with TNM stage, degree of differentiation, invasion depth and lymph node metastasis (χ² =9.643, 14.908, 16.294, 10.222, respectively, P = 0.002, 0.001, 0.000, 0.001). In the ninety patients, the 5-year survival rates of cases with positive and negative expression of FBXW7 protein was 67.6% and 39.3%, respectively (χ² =6.699, P = 0.01).

CONCLUSIONSThe results of this study demonstrate that FBXW7 expression is significantly declined in ESCC and high grade intraepithelial neoplasia tissues, and is closely correlated with poor prognosis of this disease. FBXW7 as a tumor suppressor gene may play an important role in the carcinogenesis, development and metastasis of ESCC. These results suggest that FBXW7 may become a valuable marker for the severity and prognosis in ESCC.

Biomarkers, Tumor ; metabolism ; Blotting, Western ; Carcinoma, Squamous Cell ; diagnosis ; metabolism ; Cell Cycle Proteins ; genetics ; Down-Regulation ; Esophageal Neoplasms ; diagnosis ; metabolism ; F-Box Proteins ; genetics ; F-Box-WD Repeat-Containing Protein 7 ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Staging ; Prognosis ; RNA, Messenger ; Survival Rate ; Ubiquitin-Protein Ligases ; genetics

Objective To investigate the expression and clinical significance of endoplasmic reticulum protein 29(ERp29) in colorectal cancer. Methods Paraffin-embedded sections from 62 cases of colorectal cancer tissues were obtained and used for immunohistochemical staining of ERp29. The clinical and pathological data of various levels of ERp29 in patients with colorectal cancer were analyzed to determine if there was a significant difference. Results The expression of ERp29 in 62 cases of colorectal cancer tissues, 24(38. 7％ ) cases were positive and 38(61. 3％ )cases were negative. The expression of ERp29 in 62 cases of adjacent tissues, 58 (93. 5％ ) cases were positive and 4(6. 5％ ) cases were negative. There was a significant difference in TNM classification and lymph node metastasis between ERp29 positive group and ERp29 negative group (P ＜ 0. 05 ). Conclusion Colorectal cancer tissues have significantly lower levels of ERp29 than adjacent tissues. ERp29 may be helpful to evaluate the metastatic proclivity and prognosis of colorectal cancer.

Objective To evaluate the expression of FBXW7 in esophageal squamous cell carcinoma ( ESCC) and to explore the correlation of FBXW7 expression with clinicopathologic features and prognosis of ESCC.Methods Ninety cases of ESCC and twenty cases of tumor-adjacent normal tissues and forty intraepithelial neoplasia tissues were detected by immunohistochemistry methods.The expression of FBXW7 in 40 surgical ESCC tissues and tumor-adjacent normal tissues was detected by Western blotting and RT-PCR.The relationship between the expression of FBXW7, clinicopathological characteristics and prognosis was analyzed.Results The positive rate of FBXW7 protein was significantly lower in the ESCC and high-grade intraepithelial neoplasia tissues than in the tumor-adjacent normal tissues and low grade intraepithelial neoplasia tissues (40.0%and 33.3%vs.85.0%and 77.3%, χ2=21.923, P<0.001) .The FBXW7 protein was down-regulated in ESCC tissues ( P<0.05) , whereas the FBXW7 mRNA was down-regulated in ESCC tissues compared with that in the paracancerous tissues.The expression of FBXW7 was significantly correlated with TNM stage, degree of differentiation, invasion depth and lymph node metastasis (χ2=9.643, 14.908, 16.294, 10.222, respectively, P=0.002, 0.001, 0.000, 0.001).In the ninety patients, the 5-year survival rates of cases with positive and negative expression of FBXW7 protein was 67.6%and 39.3%, respectively (χ2=6.699, P=0.01) .Conclusions The results of this study demonstrate that FBXW7 expression is significantly declined in ESCC and high grade intraepithelial neoplasia tissues, and is closely correlated with poor prognosis of this disease.FBXW7 as a tumor suppressor gene may play an important role in the carcinogenesis,development and metastasis of ESCC .These results suggest that FBXW7 may become a valuable marker for the severity and prognosis in ESCC.

Objective To evaluate the expression of FBXW7 in esophageal squamous cell carcinoma ( ESCC) and to explore the correlation of FBXW7 expression with clinicopathologic features and prognosis of ESCC.Methods Ninety cases of ESCC and twenty cases of tumor-adjacent normal tissues and forty intraepithelial neoplasia tissues were detected by immunohistochemistry methods.The expression of FBXW7 in 40 surgical ESCC tissues and tumor-adjacent normal tissues was detected by Western blotting and RT-PCR.The relationship between the expression of FBXW7, clinicopathological characteristics and prognosis was analyzed.Results The positive rate of FBXW7 protein was significantly lower in the ESCC and high-grade intraepithelial neoplasia tissues than in the tumor-adjacent normal tissues and low grade intraepithelial neoplasia tissues (40.0%and 33.3%vs.85.0%and 77.3%, χ2=21.923, P<0.001) .The FBXW7 protein was down-regulated in ESCC tissues ( P<0.05) , whereas the FBXW7 mRNA was down-regulated in ESCC tissues compared with that in the paracancerous tissues.The expression of FBXW7 was significantly correlated with TNM stage, degree of differentiation, invasion depth and lymph node metastasis (χ2=9.643, 14.908, 16.294, 10.222, respectively, P=0.002, 0.001, 0.000, 0.001).In the ninety patients, the 5-year survival rates of cases with positive and negative expression of FBXW7 protein was 67.6%and 39.3%, respectively (χ2=6.699, P=0.01) .Conclusions The results of this study demonstrate that FBXW7 expression is significantly declined in ESCC and high grade intraepithelial neoplasia tissues, and is closely correlated with poor prognosis of this disease.FBXW7 as a tumor suppressor gene may play an important role in the carcinogenesis,development and metastasis of ESCC .These results suggest that FBXW7 may become a valuable marker for the severity and prognosis in ESCC.

OBJECTIVE：To explore the new management model of Good Clinical Practice （GCP）trial drug dispensing . METHODS：Base on the relevant experience of Pharmacy Intravenous Admixture Services （PIVAS）in daytime chemotherapy center（“daytime PIVAS ”for short ）of our hospital ，the nodes and other matters needing attention were discussed in the workflow of confirmation and development of drug dispensing tasks for clinical trials. RESULTS ：After the successful approval of the new clinical trial ，the supervisor of the sponsor and the principal investigator should first confirm whether the drugs involved in the project needed to be centrally dispensed in the daytime PIVAS ，and then submitted the relevant data to PIVAS for filing. Daytime PIVAS pharmacists could participate in trial drug dispensing of relevant projects only after starting training and authorization. After the doctor issued the medical order for the subjects in the hospital information system ，the research nurse took the drugs out of the GCP pharmacy and handed them to the daytime PIVAS drug receiving window. After receiving the drugs ，the pharmacist would check the dispensing ，and then the preparation pharmacist trained and authorized by the project team would mix and dispense the drugs. The reviewed pharmacist would check and label the prepared infusion. In addition ，daytime PIVAS would regularly summarize the feedback information on the trial drug dispensing and fund management in all links of dispensing process ，so as to improve the standardization of the process. CONCLUSIONS ：Daytime PIVAS for clinical trial drug can arrange batches more rationally，ensure smooth and orderly infusion ，and meet different drug stability requirements ，which can improve trial drug dispensing management and further promote the development of drug clinical trial projects in China.