Poly(ADP-ribose) polymerase(PARP) is a protein-modifying and nucleotide-polymerizing enzyme. As a critical element in DNA repair, PARP can be activated by DNA strand breaks. Excessive activation of PARP, however, can deplete NAD + and ATP, leads to cell death. Cleavage of PARP by activated caspase-3 play an important role in cell apoptosis.

AIM and METHODS: to elucidater the effect of poly(ADP-ribose) polymerase(PARP) on tracheal hyperreactivity of guinea - pig induced by peroxynitrite, the responses of guinea pig tracheas to histamine af- ter incubation with peroxynitrite in the absence and presence of 3 - aminobenzamide(3 - AB), a highly selective inhibitor for PARP, were observed in vitro. RESULTS: The exposure of tracheal strips to peroxynitrite led to epithelial damage and hyperreacitivity to histamine, both of which were reversed by 3 - AB(l mmol/L or 5mmol/L), whereas incubation of tracheal strips with 3 - AB(5 mmol/L) had no effect on the reponses. CONCLUSION:PARP is involved in the epithelial damage and hyperreactivity of guinea - pig tracheas induced by peroxynitrite. The results suggested that inhibition of excessive activation of PARP may represent a novel strategy for the prevention and therapy of airway hyperreactivity in asthma.

AIM: To study the mechanism responsible for ONOO --induced the airway epithelial injury. METHODS: Effects of 3-aminobenzamide(3-AB), a poly-(ADP-ribose) polymerase(PARP) inhibitor, and Ac-DEVD-CHO, a caspase-3 inhibitor, on LDH release and apoptosis of cultured rat tracheal epithelial (RTE) cells induced by ONOO - were examined. The cleavage of PARP was analysed by Western blot. RESULTS: 3-AB inhibited the release of LDH induced by ONOO - partially, and had no effect on the apoptosis of RTE cells. Caspase-3 inhibitor Ac-DEVD-CHO obviously prevented the apoptosis of RTE cells induced by ONOO - in a dose-dependent manner. The cleavage of PARP was observed in the process of apoptosis of RTE cells induced by ONOO -. CONCLUSIONS: PARP activation represents one of the pathways of ONOO --mediated epithelial injury, and the excessive activation of PARP contributes to the necrosis in RTE cells induced by ONOO -. Cleavage of PARP by activated caspase-3 plays a crucial role in the apoptosis of RTE cells induced by ONOO -.

AIM:To study the effect of ONOO- on the airway epithelial injury. METHODS: The mitochondrial respiration, the amount of lactate dedydrogenase (LDH) release into the cell culture medium, the levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), and the cellular apoptosis were examined after exposure of cultured rat tracheal epithelial (RTE) cells to ONOO-. RESULTS: Exposure of RTE cells to 0.25, 0.5 and 1 mmol/L ONOO- caused a dose-dependent suppression of the mitochondrial respiration . ONOO- also caused a dose-dependent increase in the percentage of LDH release. Exposure of RTE cells to ONOO- resulted in an increased generation of 8-OHdG in a dose-dependent manner. ONOO- caused an increase in apoptotic percentage in RTE cells in a time-dependent manner at different concentrations. CONCLUSION: ONOO- could cause necrosis and apoptosis in cultured RTE cells. Low concentration of ONOO- caused apoptosis in a time-dependent manner. Whereas exposure to high concentration of ONOO- resulted in cell necrosis, ONOO- caused a dose-dependent increase in the percentage of LDH release. Suppression of mitochondrial respiration and oxidative DNA damage by ONOO- may be the major cause of cellular injury induced by ONOO-.

Objective To determine the central venous pressure (CVP) noninvasively based on hemodynamics principles using ultrasound location of the collapse point of the internal jugular vein.Methods Forty patients were enrolled in this study.The collapse point of the internal jugular vein was located and marked by a linear transducer,the body mark of right atrium was marked on the right lateral wall of the chest.The noninvasive CVP was calculated according to the vertical distance between those two points.The invasive CVP determination by central venous catheter was also carried out on all the patients.Correlation analysis was used to compare the invasive and noninvasive methods.With invasive determination of CVP as the gold standard,the ROC curve of the noninvasive ultrasound method was sketched to explore the optimal cut-off points.Results The correlation analysis reveal high positive correlation between CVPs determined by ultrasound imaging and central venous catheter (r =0.906,P ＜0.01).By the ROC curve test,fluid column height of 10.75 cm by ultrasound method was determined as the cut-off point,with the sensitivity and specificity of diagnosing elevation of CVP being 88.9％ and 93.5 ％ respectively.The corresponding area under the curve was 0.971.Conclusions Ultrasound imaging could be used to determine CVP noninvasively,which would be helpful in diagnosis of the circulating load of patients.

Objective To propose an accurate method of noninvasive determination of central venous pressure(CVP ) by locating the central point of right atrium (RA ) using echocardiography .Methods Through the 3D reconstruction ,the accurate positions of RA of 30 patients who had been examined by multislice 3‐dimensional computed tomography for chest imaging were recorded .Based on solid geometric principles ,the central point in RA was located by echocardiography and then compared with CT‐location point .The accuracy and feasibility were assessed by absolute distance (Da) ,vertical distance (Dv) and the whole time of location (T) between the two points .Results Mean Da ,Dv and T of the whole subjects were 07.6cm(95% CI:06.2to08.1cm),01.6cm(95% CI:-00.2to03.4cm),and438.0s(95% CI:400.1to 47 4.0 s) ,respectively .Conclusions The echocardiographic method on the basis of solid geometry proposed in this study could be used to locate the central point in RA accurately and simply .Thus it would be helpful to improve the accuracy of noninvasive determination of central venous pressure .

Objective:To study the relationship between the expression of filamin A (FLNa) and clinical pathological features in invasive breast carcinoma. Methods:The expression of FLNa was measured by immunohistochemistry and flow cytometry in 46 cases of invasive breast carcinoma. Results:The expression level of FLNa was increased in poorly differentiated invasive breast carcinoma. There were significant differences between well-moderately differentiated and poorly differentiated groups (P<0.05). The expression level of FLNa in invasive breast carcinoma with lymph node metastasis was higher than that in non-metastasis group (P<0.05). Conclusion:The level of FLNa expression correlated with invasion and metastasis of invasive breast carcinoma. FLNa can be used as an assistant marker for prediction of breast carcinoma prognosis and has the potential to be a new target for cilinical therapy.

Objective To analyze the levels and clinical significances of IL-18,Caspase-3 and nerve tissue-specific protein S-100B at different disease extent and different stages of infants with hypoxicischemic encephalopathy (HIE).Methods This study was clinical experimental studies.Sixty-seven infants with HIE (23 cases of mild HIE,23 cases of moderate HIE,21 cases of severe HIE) from February 2008 to June 2009 in Hebei Children's Hospital were enrolled.The levels of IL-18,Caspase-3 and S-100B protein in all samples were measured at acute phase (1 d,3 d) and recovery phase (7 d) by ELISA method.Twenty healthy full-term neonates were selected as the normal control group.Multi-factor analysis of variance and Pearson correlation test was used for statistical analysis.Results The levels of the three indicators in the moderate and severe group were higher than the normal control group.In the moderate group,IL-18 levels were(132.15 ± 9.87),(150.31 ± 15.04) and (87.91 ± 9.93) ng/L,Caspase-3 levels were (5.79 ±0.64),(7.36 ± 1.57)and (3.79 ±0.61) μg/L,S-100B levels were(6.82 ±0.61),(9.62 ± 1.29) and (10.76 ± 1.64) μg/L.In the severe group,IL-18 levels were (160.23 ± 16.03),(189.86 ± 18.32) and (107.35 ± 13.02) ng/L;Caspase-3 levels were (6.86 ± 1.02),(9.54 ± 1.43) and (5.25 ± 0.71) μg/L;S-100B levels were(8.90 ± 0.32),(12.54 ± 0.89)and(13.53 ± 0.75) μg/L.In the normal control group,IL-18 levels were (71.08 ± 11.52),(72.53 ± 11.05) and (71.93 ± 11.30) ng/L; Caspase-3 levels were (2.84 ± 0.52),(2.98 ± 0.53) and (2.87 ± 0.52) μg/L; S-100B levels were (1.50 ± 0.25),(1.62 ±0.30)and(1.53 ±0.29) μg/L IL-18 levels,Caspase-3 levels and S-100B levels in severe group were higher than the moderate group and the mild group were higher than the mild group.IL-18 levels were (73.46 ± 4.77),(77.59 ± 4.02) and (72.87 ± 6.92) ng/L ; Caspase-3 levels were (3.13 ± 0.31),(3.63±0.40) and (3.26 ±0.45) μg/L;S-100B levels were(3.68 ±0.40),(5.851 ±0.63) and(6.95 ± 0.58) μg/L in the mild group.S-100B levels in the mild group were higher than that in the normal control group.The IL-18 and Caspase-3 levels were risen in the third day to the first day in the acute phase of the moderate group and severe group,decreased in the recovery phase.Serum S-100B protein levels in the acute and recovery phase increased gradually,and there was no correlation between the three indicators (r-=0.321,0.14,0.48,P=0.438,0.974,0.911 respectively).Conclusions IL-18,Caspase-3 and S-100Bwere involved in the pathophysiological process of HIE.The levels were closely related to the severity and disease progression of HIE,the severer of the illness,and the higher of the levels.Dynamic monitoring the changes of the three indicators may contribute to an early diagnosis,condition monitoring and prognosis of HIE.

BACKGROUNDTo study the correlation among the number of tumor-infiltrating dendritic cells (TIDC) in cancer tissues and biological behavior and prognosis in lung cancer patients.

METHODSS-100 protein expression level was determined in 39 patients with lung cancer by immunohistochemistry technique. The number of S-100 + TIDC and DNA ploidy were measured by means of flow cytometry.

RESULTSThe rate of positive S-100 protein expression was 100% in 39 patients, S-100 + cells showed typical morphology of dendritic cells. The percentage of S-100 +TIDC in patients with heteroploid (21.81%±8.18%) was significantly higher than those with diploid (16.03%±4.75%) (P=0.006). There was no statistical difference between lymph node metastasis group (20.43%±7.74%) and no lymph node metastasis group ( 19.41% ±7.76%), between tumor size greater than 3cm group ( 20.90% ±8.65%) and less than 3cm group ( 19.70% ±7.61%), between non-small cell lung cancer group (19.48%±7.98%) and small cell lung cancer group (21.74%±6.17%). No correlation was found between survival time ( 1 year , 1-3 years, greater than 3 years, respectively) and percentage of S-100 +TIDC (21.96%±8.05%, 19.47%±6.18%, 19.14%±8.76%, respectively).

CONCLUSIONSThe number of TIDC should not be chosen as an independent prognostic criterion in human lung cancer.

OBJECTIVE: To filtrate and prove the different microRNAs (miRs) profiles in nasopharyngeal carcinoma. METHOD: Screening the different expressions of miRs between nasopharyngeal carcinoma and the inflammatory tissues by the application of expression profiling of chip high-throughput and large-scale microarray analysis. Then we used RT-QPCR technology to prove the accuracy of screening results. RESULT: There were significant expression differences of miRs between nasopharyngeal carcinoma and the control tissues, 144 human miRs had 2 or more fold the difference ratio. Compared with the inflammatory tissues, we have found that miRs-34b, miRs-449b and miRs-7-1 significantly low expressed in nasopharyngeal carcinoma, yet miRs-125b, miRs-184, miRs-196b, miRs-205 and miRs-24-1 expressed high. The results were consistent with the microarray analysis. CONCLUSION The difference expressed miRs might be closely related to the process of nasopharyngeal carcinoma, and the research on miRs profiles maybe provide a powerful target basis for early diagnosis and therapy of nasopharyngeal carcinoma.
Carcinoma ; Gene Expression Profiling ; Humans ; MicroRNAs ; genetics ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; genetics ; Oligonucleotide Array Sequence Analysis