Objective To compare the efficacy and toxicity of late-course concurrent radiochemotherapy and sequential chemoradiotherapy for advanced esophageal carcinoma. Methods Eighty-two patients with advanced esophageal carcinoma were randomized into two groups: 41 cases in late-course concurrent radiochemotherapy (LCRC) group were received two cycles chemotherapy and then underwent concurrent radiochemotherapy;41 cases in sequential chemoradiotherapy (SCR) group were received four cycles chemotherapy and then underwent radiotherapy. The regimen of chemotherapy in all cases:cisplatin 25mg/m2, 1-3 d;calcium folinate (CF) 150 mg/m2, 1-5 d;fluorouracil 375 mg/m2, 1-5 d, 21 d was one cycle. All patients were received the three-dimensional conformal radiation therapy, the total dose of radiation was same as 64 Gy. Results The short-term response rate was 85.4%(35/41) in LCRC group and 65.9%(27/41) in SCR group, they had significant difference ( P<0.05). The rates of acute radiation esophagitis that need treatment was 90.2%(37/41) in LCRC group and 87.8%(36/41) in SCR group, there had no significant difference (P>0.05). The l year, 2 years, 3 years survival rate were 68.3%(28/41) and 65.9%(27/41), 56.1%(23/41) and 51.2%(21/41), 46.3%(19/41) and 36.6%(15/41) respectively,the median survival time were 30.0 months and 26.0 months, there had no significant difference ( P>0.05). Conclusion The short-term efficacy of advanced esophageal carcinoma could be improved by the late-course concurrent radiochemotherapy.

Objective To explore the feasibility of evaluation of mice hind limb ischemia-mediated angiogenesis with ultrasound molecular imaging using molecular probes targeted to angiogenesis endothelial marker VEGFR-2.Methods A mice model of unilateral hind-limb ischemia was induced by femoral artery excision in 12 experimental mice.Ultrasound molecular imaging of the ischemia and contralateral non-ischemia hind-limbs was performed in all mice on day 7 after surgery at 8 minutes after intravenous injection of either VEGFR-2 targeting microbubbles or isotype control microbubbles in random with 30 min interval,and the video intensity (VI) was measured.Following ultrasound imaging,the hind-limb was harvested for immunohistochemical analysis.Results As expected,VI in the ischemia hind-limb was significantly higher (P ＜0.05) for MBvEGFR-2 [(25.6 ± 4.3)U] as compared with MBIso[(6.7 ± 1.6)U].However,the ultrasound signal in the non-ischemia hind-limb was low for both MBvEGFR-2 [4.4 ± 1.5)U] and MBIso [(4.6 ± 1.6)U].A marked endothelial VEGFR-2 expression in ischemia hind-limb was confirmed by immunohistochemistry.Conclusions Ultrasound molecular imaging using molecular probes targeted to angiogenesis endothelial VEGFR-2 can effectively evaluate ischemia-mediated angiogenesis.

Purpose To discuss the clinical,histopathological characteristics,diagnosis,differential diagnosis and prognosis of malignant intraductal papillary lesions of the breast.Methods 28 cases of malignant intraductal papillary lesions of the breast were analyzed by histology and immunobistochemistry.Clinical and follow-up information was obtained.The published relevant literatures were reviewed.Results All the patients were females with a mean age of 55.7 years.The clinical features were a palpable mass or nipple discharge.28 cases were diagnosed including 22 cases of intraductal papaillary carcinoma,2 cases of encapsulated papillary carcinoma and 4 cases of solid papillary carcinoma.Microscopically,the tumor showed solid and papillary area inside the capsule wall with fine delicate fibrovascular septa.The tumor cells usually displayed low-grade nuclear features.Immunohistochemistry,the tumor cells revealed diffusely strong positive ER and PR in almost all cases and HER-2,CK5/6 were negative positive.All cases were negatiive for CK5/6,p63 and SMA in the celluar nodules.CD56,Syn and CgA were found positively in some solid papillary carcinoma cases.The average positive rate of Ki-67 in tumor cells was 5.3 ％.27 patients were available for follow-up examination from 10 to 79 months and all the patients were alive.Conclusion Malignant intraductal papillary lesions of the breast most occurs in postmenopausal women.The diagnosis should be based on the clinical information,histopathological features and immunohistoehemistry stain due to its diverse histology.The main differential diagnosis is intraductal papilloma.This kind of lesion is a low grade malignant tumor with favorable prognosis.

Objective To explore the effect and mechanism of renal denervation combined with Losartan on cardiac hypertrophy in spontaneous hypertensive rats. Methods Spontaneous hypertensive rats with cardiac hypertrophy underwent renal denervation combined with following 4 weeks drug treatments. Transthoracic two-dimensional guided M-mode echocardiography was performed. The expression of hypertrophy-related gene was detected. Left ventricularmass index was calculated and histological sectionsstained with hematoxylin and eosin (HE). Results The characteristics of cardiac hypertrophy was observed in left ventricular tissues with HE staining in12 weeks old spontaneous hypertensive rats.The thickness was increased in those ventricular (IVSs, IVSd, LVPWs and LVPWd). After4 weeks after treatment, histological improvements were observed in both RDN and R+L groups compared with sham group. The improvement was more obvious in R+L group. Similar results were observed in histological sections, ventricular thicknesses (IVSs, IVSd, LVPWs and LVPWd), related-hypertrophy genes (ANP and β-MHC) expression, left ventricular mass idex (LVMI) and the protein expression of inflammatory cytokines (TNF-α and IL-6). Conculsion Renal denervation therapy can improve hypertensive-induced cardiac hypertrophy in spontaneous hypertensive rats. The effect was more significant when combined with Losartan. The mechanism might be involved in inhibiting inflammatory cytokines.

Objective To explore the effects of miRNA-204 targeted LC3B expression on Ang Ⅱ induced cardiomyocytes hypertrophy.Methods The primary neonatal rat cardiomyocytes served as the research objects and divided into the control group,AngⅡ group,combination-treated group 1 (cardiomyocytes were given Ang Ⅱ stimulation,meanwhile infected by negative control lentivirus vector),combination-treated group 2 (cardiomyocytes were given Ang Ⅱ stimulation,meanwhile infected by lentivirus carrying miRNA-204 overexpression vector) according to different treatments.About 48 h to 72 h after intervention treatment,the cardiomyocyte hypertrophy change was detected by confocal microscopy,the expression of miRNA-204 was analyzed by real time PCR,the protein expression of LC3B was measured by Western blot and targeted gene of miRNA-204 was demonstrated by dual-luciferase reporter assay system.Results Compared with the control group,the cardiomyocyte relative surface area in the Ang Ⅱ group was significantly enlarged,the protein expression of LC3B was significantly increased,the expression of miRNA-204 was upregulated,the differences were statistically significant (P＜0.05).Whereas comparing the combination-treated group 1 with combination-treated group 2,the protein expression of LC3B in the latter was down-regulated and the cell area was reduced (P＜0.05).The further luciferase activity report gene experiment results suggested that miRNA-204 was able to bind to LC3B 3'-UTR and decreased the luciferase activities (P＜0.05),but not to bind its mutated fragment for inactivating luciferase activity(P＞0.05).Conclusion miRNA-204 is able to inhibit Ang Ⅱ induced cardiomyocytes hypertrophy,its action is realized by targeting the expression of LC3B.

BACKGROUND: Acidic peptide is the tripeptide composed of 3 glutamic acids, which cannot bring excitatory nerve signal transmission into playlike single glutamic acid through presynaptic release and integration withpostsynaptic NMDA receptor directly as excitable neurotransmitter. It is quite possible that acidic peptide plays its actions by integrating with multiple metabolic glutamic acidic receptors so as to promote neuron proliferation or release nerve growth factor (NGF). OBJECTIVE: To probe into whether acidic peptide induces changes in learning and memory of model rats with Alzheimer disease (AD).DESIGN: Randomized controlled single experiment was designed.SETTING: Teaching-Research Room of Biochemistry and Molecular Biology of Basic Medical College of Zhengzhou University.MATERIALS: The experiment was performed in 2nd Research Room and Experimental Animal Room of Teaching-Research Room of Biochemistry and Molecular Biology of Basic Medical College of Zhengzhou University.Totally 100 SD male rats were selected and some of them were excluded due to retarded response in step down test. Totally 84 rats were included in the experiment and randomized into 7 groups, named normal control,model group, physiological saline group (PS group), piracetam group, acidic peptide groups of 60, 30 and 15 mg/kg, 12 rats in each group. Acidic peptide is a new small molecular peptide separated from bovine brain in this research team and is tripeptide composed of three glutamic acids.METHODS: Except normal control, in the rest groups, after 1 week routine breeding, cerebral stereotactic microinjection was used to inject 5 μg ibotenic acid in hippocampus of rats to destroy bilateral Meynert's basal ganglia to establish AD model. In normal control and model group, no medication was applied. In PS group, physiological saline was used for gastric perfusion. In piracetam group, piracetam of 0.3 g/kg was used for gastric perfusion and in acidic peptide groups of 15, 30 and 60 mg/kg,acidic peptide of 60, 30 and 15 mg/kg was applied for gastric perfusion successively, continuously for 20 days, once per day, 2 mL/time. On the expiration of gastric perfusion, learning and memory of rats were examined with step down test in every group. The animal was placed on the safe table on step down platform to adapt to the environment for 3 minutes, afterwards, 36 V electric current was given. Error response was recorded if the animal jumped to the copper railings after electric shock and correct response was recorded if the animal jumped back the safe area. Step-up latent phase and frequency of correct response were recorded in 3 minutes.MAIN OUTCOME MEASURES: Comparison of learning and memory of rats in every group. RESULTS: Totally 84 rats were all included in the result analysis. ①Comparison of learning in every group: Compared with model group, stepup latent phase was shortened remarkably in every acidic peptide group[(102.03±5.33), (71.77±4.38), (68.28±9.53), (69.13±8.79) s, P ＜ 0.01] and the frequency of correct response was improved remarkably [(12.92±2.91),(16.17±2.79), (15.83±3.27), (16.33±2.53) times, P ＜ 0.01]. ② Comparison of memory in every group: Compared with model group, step-up latent phase was shortened remarkably in every acidic peptide group [(43.17±4.66),(29.78±4.48), (26.20±3.28), (22.09±4.43) s, P ＜ 0.01] and the frequency of correct response was improved remarkably [(15.67±2.15), (20.92±2.68),(20.83±2.29), (20.25±2.05) times, P ＜ 0.01].CONCLUSION: Acidic peptide can shorten remarkably the step-up latent phase of AD rats in step down test and improve the frequency of correct response. It is indicated that acidic peptide provides good intervention on learning and memory of rat model of Alzheimer disease.

Objective To observe the effect of heat shock protein 70 (HSP70) expression induced by Herba Hedyotis Diffusae (HHD) on the apoptosis of H22 hepatoma cells.Methlds Mice were immunized with H22 hepatoma cells from in-vivo ascites of the mice pretreated by HHD and Radix Codonopsis (RC).Mice were divided into five groups after being blocked with HSP70 monoclonal antibody:non-HHD blocking group,HHD blocking group,non-RC blocking group,RC blocking group and the blank control group,10 mice in each groups.Then the mice were attacked with cultured H22 hepatoma cells to induce transplanted tumor.The apoptosis in the transplanted tumor was detected by a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) method.Results Large amount of brown particles can be observed in the cell nucleus of transplanted tumor mice from HHD groups.Compared with RC groups,number of apoptotic cells and the staining intensity were increased in HHD groups.The apoptosis in HHD groups and RC groups differed from that in the blank control group,and was obvious in HHD groups.The apoptosis exerted a increasing tend in non-HHD blocking group,but the difference was insignificant between non-HHD blocking group and HHD blocking group,and between non-RC blocking group and RC blocking group.Conclusion HHD can promote the apoptosis of H22 hepatoma cells in transplated tumor through inducing the expression of HSP70 to some extent,and the related mechanism of inducing apoptosis needs further research.

Objective To assess the early prognosis of 117 patients after carduopulmonary resuscitation (CPR) in ICU by using the markers of inflammation,Glasgow Coma Scale (GCS) and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) scores.Methods A total of 117 CPR patients admitted between 2010 January to 2012 December were enrolled for study.Within 24 h after admission,inflammatory markers,blood routine items,hepatorenal function,electrolytes of blood were measured.The GCS and APACHE Ⅱ scores were recorded.Arterial blood gas analyses were performed at 0,12,and 24 h after hospitalization,and the 12-h and 24-h lactate clearance rates were calculated.Seven days after treatment,according to the outcomes,the patients were divided into survival group and death group,and the clinical data of two groups were analyzed.Results (1) Of them,73 patients died and 44 survived.Factor analysis showed that age,time elapsed from resuscitation to ICU admission,D-dimer,arterial oxygenation index (FiO2),arterial blood pH,arterial blood lactate concentration upon ICU admission,GCS score and APACHE Ⅱ score were significantly different between the two groups (P ＜ 0.05or P ＜ 0.01); (2) Two classification logistic regression analysis showed that D-Dimer,GCS score and APACHE Ⅱ score significantly correlated with the mortality risk of the patients in the wake of CPR with relative odds ratios of 1.000,2.091,and 0.531,respectively (P ＜ 0.05 or P ＜ 0.01) ; (3) Receiver operating characteristic curve analysis indicated that the area under the curve of GCS (0.821) and APACHE Ⅱ (0.869) had higher predictive value than D-dimer (0.655).The highest accuracy (84.6％) in predicting patient survival was achieved when the GCS score was 6.5.Meanwhile,the highest accuracy (82.1％) in predicting patient death was achieved when the APACHE Ⅱ score was 17.5.Conclusions Both GCS score and APACHE Ⅱ score has obvious correlation with the prognosis of the critically ill patients after CPR and could be used to predict prognosis at early stage.

BACKGROUND: Nerve growth factor (NGF) and brain-derived neurotrophic factor(BDNF) are very important to the survival and proliferation of nerve cells. In the patients with Alzheimer disease (AD), the levels of NGF and BDNF are low.OBJECTIVE: To investigate whether acidic peptide can stimulate rat astrocytes to secrete NGF and BDNF.DESIGN: A randomized control animal experiment.MATERLALS: The experiment was finished in the First Laboratory of Institute of Biopeptide, Zhengzhou University; Cellular Culture Center,School of Basic Medical Sciences of Zhe ngzhou University from September 2003 to May 2005. Fifteen neonatal SD rats within 2 days after birth were selected.METHODS: ① The cerebral cortex of the neonatal SD rats was removed under sterile condition, the astrocytes were isolated and cultured, and then identified with the glial fibriliary acidic protein immunohistochemical staining. ② The cultured astrocytes were randomly divided into six group:blank control group, serum control group, positive control group and acidic peptide treated groups. No treatment was given in the blank control group,serum of 0.2 in volume fraction and 1 000 U/mL interferon were added in the serum control group and positive control.group, 37.5, 75 and 150 mg/L acidic peptides were added in the acidic peptide treated groups respectively. ③ The astrocytes of the 2nd generation, which covered the whole bottom of bottle, were digested to single cell suspension, and then inoculated to three 12-well plates equally at 5×105 /mL. The survival rate and the contents of NGF and BDNF in the supernatant of each group were determined at 24, 48 and 72 hours respectively.MAIN OUTCOME MEASURES: ① Cell numbers and survival rates at different culture time-points; ② Effect of acidic peptide on the proliferation of astrocytes in rats; ③ Changes of NGF and BDNF in the supernatant of astrocytes at different culture time-points.RESULTS: ① As compared with the blank control group, the cell numbers and survival rates at 24, 48 and 72 hours were obviously increased in the acidic peptide groups treated with 75 and 150 mg/L (P＜0.05, 0.01,0.001), but not obviously increased in the acidic peptide group treated with 37.5 mg/L. ② As compared with the blank control group, the rates of proliferation in the acidic peptide groups treated with 37.5, 75 and 150 mg/L were all significantly increased (17.5%, 45.5%, 72.5%, P＜0.001). ③ As compared with the blank control group, the absorbance (A) values of NGF in the supernatant at 24, 48 and 72 hours were all markedly increased in the acidic peptide groups treated with 37.5, 75 and 150 mg/L (P＜0.001),and the A values of BDGF in the supernatant at 48 and 72 hours were significantly increased (P＜0.05, 0.01).CONCLUSION: Acidic peptide can increase the secretions of NGF and BDNF of rat astrocytes to different extent.

Objective To explore the effects of miR-34a and the alteration of AMPK/mTOR signal pathway on angiotensin (Ang)Ⅱ-stimulated cardiomyocytes hypertrophy. Methods Neonatal rat cardiomyocytes were cultrued in vitro and were divided into 3 groups:negative control for lentivirus carrying miR-34a group (NC), AngⅡplus lentivirus carrying negative control group (AngⅡ+NC) and AngⅡplus lentivirus carrying miR-34a group (AngⅡ+miR-34a). The relative cell area was detected by confocal microscopy. The expression of miR-34a and hypertrophy-related genes (ANP and β-MHC) were analyzed by real time PCR. The AMPK/mTOR signal pathway was measured by Western blot assay. Results Compared to NC group, the relative cell area was increased in AngⅡ+NC group (P<0.05). But compared with AngⅡ+NC group, the relative cell area was decreased in AngII+miR-34a group (P<0.05). Moreover, compared with NC group, the expression of miR-34a was decreased, and the expression of hyperthophy-related genes(ANP and β-MHC) was up-regulated in AngⅡ+NC group. However, the expression of miR-34a was decreased, and the expression of hyperthophy-related genes (ANP and β-MHC) was down-regulated (P<0.05). Finally, compared to NC group, the ratio of phosphop-AMPK/AMPK was significantly induced in AngII + NC group, but the ratio of phosphop-mTOR/mTOR was significantly decreased (P<0.05). However, compared to AngⅡ+NC group, the ratio of phosphop-AMPK/AMPK was significantly decreased in AngII + miR-34a group, but the ratio of phosphop-mTOR/mTOR was significantly increased (P<0.05). Conclusion miR-34a is able to inhibit myocardial hypertrophy of neonatal rat cardiomyocytes, and its mechanism is partly carried out by the alteration of the signal pathway of AMPK/mTOR.