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Purpose@#While several prognostic models for the stratification of death risk have been developed for patients with advanced gastric cancer receiving first-line chemotherapy, they have seldom been tested in the Chinese population. This study investigated the performance of these models and identified the optimal tools for Chinese patients. @*Materials and Methods@#Patients diagnosed with metastatic or recurrent gastric adenocarcinoma who received first-line chemotherapy were eligible for inclusion in the validation cohort. Their clinical data and survival outcomes were retrieved and documented. Time-dependent receiver operating characteristic (ROC) and calibration curves were used to evaluate the predictive ability of the models. Kaplan-Meier curves were plotted for patients in different risk groups divided by 7 published stratification tools. Log-rank tests with pairwise comparisons were used to compare survival differences. @*Results@#The analysis included a total of 346 patients with metastatic or recurrent disease.The median overall survival time was 11.9 months. The patients were different into different risk groups according to the prognostic stratification models, which showed variability in distinguishing mortality risk in these patients. The model proposed by Kim et al. showed relative higher predicting abilities compared to the other models, with the highest χ 2 (25.8) value in log-rank tests across subgroups, and areas under the curve values at 6, 12, and 24 months of 0.65 (95% confidence interval [CI]: 0.59–0.72), 0.60 (0.54–0.65), and 0.63 (0.56–0.69), respectively. @*Conclusions@#Among existing prognostic tools, the models constructed by Kim et al., which incorporated performance status score, neutrophil-to-lymphocyte ratio, alkaline phosphatase, albumin, and tumor differentiation, were more effective in stratifying Chinese patients with gastric cancer receiving first-line chemotherapy.
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Objective:To investigate evaluation methods to predict the outcome of nervous system development in high-risk infants. Methods:From March, 2015 to March, 2016, 336 high-risk infants were enrolled. They were assessed by General Movements (GMs) Quality Assessment, 0~1 Years Old 20 Items Neuromotor Assessment and Gesell Developmental Schedules. Results:A total of 236 infants finishied the study. GMs Quality Assessment showed that 203 cases were normal and 33 cases were abnormal in the writhing movements stage; 218 cases were normal and 18 cases were abnormal in the fidgety movemonts stage. 0~1 Years Old 20 Items Neuromotor Assessment showed that 202 cases were normal and 34 cases were abnormal. Gesell Developmental Schedules showed that 12 cases were abnormal. Conclusion:The combination of GMs Quality Assessment, 0~1 Years Old 20 Items Neuromotor Assessment and Gesell Developmental Schedules could better predict the nervous system development of high-risk infants.
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Objective To explore the value of transseptal puncture for left-sided accessory pathway in radio-frequency catheter ablation in children with paroxysmal supraventricular tachycardia(PSVT). Methods Thirty-three patients with PSVT who had underwent radiofrequency catheter ablation in the First Affiliated Hospital,Sun Yat-Sen University from January 2012 to December 2017 were retrospectively analyzed. All the cases were treated by transaortic approach(transaortic group)or transseptal approach(transseptal group). The immediate success rates,total fluoroscopy time and radiation exposure between 2 groups were compared,and the perioperative complications and recurrence rates were observed between 2 groups. Results Thirty-three cases of children were enrolled,22 cases were male and 11 cases were female. Nineteen cases were treated by transaortic approach(transaortic group),while 18 cases were treated by transseptal approach(transseptal group),including 4 recurrent cases in the transaortic group who were switched to transseptal approach because of previous treatment failure. The age was(10. 16 ± 3. 06)years and(10. 67 ± 2. 20) years,and the weight was(37. 68 ± 14. 28)kg and(37. 33 ± 8. 64)kg,respectively. There were no significant diffe-rences in age and weight statistics between 2 groups(all P>0. 05). The total fluoroscopy time was(20. 16 ± 11. 41) minutes and(12. 56 ± 5. 23)minutes,and the median dose of radiation exposure was 67. 0 mGy and 33. 5 mGy,re-spectively. The postoperative recurrence rate was 21%(4/19 cases)and 0(0/18 cases),respectively. There were sig-nificant differences in total fluoroscopy time,radiation exposure and recurrence rate statistics between 2 groups( t ＝2. 627,Z＝ -2. 31,χ2 ＝4. 249,all P<0. 05). No complications were found in both 2 groups. Conclusions It is safe and feasible by transseptal puncture for left-sided accessory pathway in radiofrequency catheter ablation in children with PSVT. Radiofrequency catheter ablation by transseptal approach could significantly reduce the postoperative recu-rrence rate,and should be the first choice for left-side accessory pathway in children.
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OBJECTIVE: The purpose of this study was to investigate whether three-dimensional (3D) magnetic resonance imaging could improve diagnostic accuracy for suspected posterior ligamentous complex (PLC) disruption. MATERIALS AND METHODS: We used 20 freshly harvested goat spine samples with 60 segments and intact surrounding soft tissue. The animals were aged 1–1.5 years and consisted of 8 males and 12 females, which were sexually mature but had not reached adult weights. We created a paraspinal contusion model by percutaneously injecting 10 mL saline into each side of the interspinous ligament (ISL). All segments underwent T2-weighted sagittal and coronal short inversion time inversion recovery (STIR) scans as well as coronal and sagittal 3D proton density-weighted spectrally selective inversion recovery (3D-PDW-SPIR) scans acquired at 1.5T. Following scanning, some ISLs were cut and then the segments were re-scanned using the same magnetic resonance (MR) techniques. Two radiologists independently assessed the MR images, and the reliability of ISL tear interpretation was assessed using the kappa coefficient. The chi-square test was used to compare the diagnostic accuracy of images obtained using the different MR techniques. RESULTS: The interobserver reliability for detecting ISL disruption was high for all imaging techniques (0.776–0.949). The sensitivity, specificity, and diagnostic accuracy of the coronal 3D-PDW-SPIR technique for detecting ISL tears were 100, 96.9, and 97.9%, respectively, which were significantly higher than those of the sagittal STIR (p = 0.000), coronal STIR (p = 0.000), and sagittal 3D-PDW-SPIR (p = 0.001) techniques. CONCLUSION: Compared to other MR methods, coronal 3D-PDW-SPIR provides a more accurate diagnosis of ISL disruption. Adding coronal 3D-PDW-SPIR to a routine MR protocol may help to identify PLC disruptions in cases with nearby contusion.
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Adult , Animals , Female , Humans , Male , Contusions , Diagnosis , Goats , Ligaments , Magnetic Resonance Imaging , Models, Animal , Protons , Sensitivity and Specificity , Spine , Tears , Weights and MeasuresABSTRACT
Discrete industry is different from the complex industry, the patent citation between enterprises is the main channel of its dominant knowledge flow. In order to help the enterprises to find the imitative innovation objects and the investors to evaluate the value of the listed companies in the discrete industries, this study took the Chinese materia medica listed companies as the research samples, first used the social network analysis method to construct the visual flow chart of knowledge flow, then the K-means clustering was carried out by using the degree centrality and the betweenness centrality of the network graph, and the type of knowledge flow was divided and summarized. Finally, based on the previous classification of the main body, the binary logistic regression was adopted to explore the influence of patent factors and business factors on the knowledge flow from two dimensions of knowledge outflow and inflow. The results showed that enterprise age, technology width, enterprise scale and R & D investment had a significantly positive correlation with the knowledge outflow; The knowledge inflow was positively relative with R & D investment and the number of claims, while with significantly negative correlation with the enterprise age, technology width, scientific relevance and technical concentration.
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Bufonis Venenum, as a precious Chinese materia medica, has complex chemical constituents and has been widely used in clinical treatment with significant effects. The chemical constituents in Bufonis Venenum mainly included bufadienolides, indole alkaloids, and steroids, etc. Modern pharmacological research has demonstrated its antitumor, cardiac, anti-inflammatory, and narcotic analgesic, etc. This paper reviewed the chemical constituents, pharmacological activity, and artificial synthesis of Bufonis Venenum, providing theoretical reference for material basic research, pharmacodynamic mechanism interpretation, development, and utilization.
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<p><b>OBJECTIVE</b>To investigate the effect of nucleolin silencing on the differentiation of rat neural stem cells (NSCs) and the role of Wnt signaling pathway in mediating such effect.</p><p><b>METHODS</b>Adenovirus vectors expressing small interfering RNA (siRNA) against nucleolin were constructed, verified, and packaged in HEK293A cells. The adenovirus was then transfected into NSCs isolated from neonatal SD rats and the differentiation of the NSCs was examined by detecting the expressions of neuron specific encloase (NSE) and glial fibrillary acidic protein (GFAP) using immunocytochemistry. The expressions of nucleolin, nestin, Wnt3, and β-catenin in the cells were determined with Western blotting.</p><p><b>RESULTS</b>Restriction endonuclease and sequencing analysis verified successful construction of the adenoviral vector expressing nucleolin siRNA (nucleolin-siRNA2). Infection of rat NSCs with nucleolin-siRNA2 significantly lowered nucleolin protein expression as compared with that in negative and blank control groups (P<0.05). The percentages of NSE-positive cells and GFAP-positive cells were significantly higher in NSCs infected with nucleolin-siRNA (P<0.01); the infection also resulted in obviously lowered expression of nestin protein and increased expressions of Wnt3 protein and β-catenin nucleoprotein in the cells.</p><p><b>CONCLUSIONS</b>Nucleolin silencing by adenovirus-mediated RNA interference induces the differentiation of NSCs into neurons and astrocytes, which is related with the activation of Wnt signaling pathway.</p>
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To summarize the breeding and identification of Wuzhishan miniature pig models with α-l,3-galactosyltransferase (GGTA1) gene-knockout (GTKO).Methods The breeding and reproduction perform of GTKO Wuzhishan miniature pigs were assessed and the quantity of piglets was counted.The GTKO Wuzhishan miniature pig models with GGTA1gene knockout were validated by polymerase chain reaction(PCR).The αGal phenotype of peripheral blood mononuclear cells (PBMC) in human,wild-type Wuzhishan miniature pigs and GTKO Wuzhishan miniature pigs was detected by fluorescent microscope and flow cytometry.Routine blood test parameters were statistically compared between the GTKO and wild-type Wuzhishan miniature pigs.Results The inheritance of GGTA1 genotype complied with Mendel's law.Flow cytometry detected no fluorescent expression of PBMC in GGTA1-/-pig models,which were consistent with the genotype identification results.The mean piglets of the primiparous GTKO Wuzhishan miniature pigs were (6.8±1.8) and (8.3±2.2) for the multiparous Wuzhishan miniature pigs.No statistical significance was noted in routine blood test parameters between the GTKO and wild-type Wuzhishan miniature pigs (all P＞0.05).Conclusions Stable inheritance and normal reproductive capacity are observed in two generations of Wuzhishan miniature pigs continuously.GTKO Wuzhishan miniature pig is a reliable donor for heterogeneous organ transplantation.
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Objective:To generate sex hormone binding globulin(SHBG) conditional knockout mice model.In order to investigate the physiological function of SHBG in vivo and to provide experimental means for the study of the relationship between SHBG and gestational diabetes mellitus.Methods:The mouse genomic DNA sequence of SHBG was verified through bioinformatic analysis.According to the SHBG genomic DNA sequence,the gene targeting and knockout vector were constructed.Transfection of the vectors to ES cells by electroporation was performed according to common protocol.Positive ES cells were screened and identified by PCR.Therefore,the dual selected ES cells were microinjected into blastula,then blastula transplantations into the host mice.The chimeric mice were mated with C57BL/6J mice,and the Flox mice were obtained after screening.The Flox mice were hybridized with EIIA-Cre transgenic mice,and the progeny of the SHBG gene knockout (SHBG-/-) mice were obtained by autocopuation for several times.Results:Several Flox homozygous mice and SHBG gene knockout mice were successfully obtained.Compared with control mice,homozygous mice of SHBG gene knockout were well developed and had reproductive ability.The growth and development of SHBG knockout mice were not significantly different from that of wild type mice.Conclusion:Homozygous mice model of SHBG gene knockout was successfully established,which laid the foundation for further study of the role of SHBG in the gestational diabetes.The SHBG gene knockout mouse model was successfully established and the preliminary phenotypic analysis was performed,which laid the foundation for further study on the role of SHBG in gestational diabetes mellitus.SHBG gene knockout mice were normal in appearance.Due to the limited number of samples and many unknown biological characteristics of gene knockout mice,it needs further study.
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Objective To investigate the effects of sex hormone-binding globulin (SHBG)gene in the apoptosis of human trophoblastic cells.Methods The siRNA specific-targeting SHBG gene was transfected into human trophoblastic cells and they were divided into six groups:trophoblasts without transfection in normal control groups(group Ⅰ);transfect liposome in blank control groups(group Ⅱ);transfect nonspecific siRNA in negative control groups(group Ⅲ);transfect SHBG siRNA-Ⅰ,SHBG siRNA-Ⅱ,SHBG siRNA-Ⅲ respectively in trans-fection group(group Ⅳ,Ⅴ,Ⅵ).Hoechst 33258 dying method was used to detect cell apoptosis.SHBG and Caspase-3 mRNA profiling and the level of SHBG and caspase-3 protein were detected by real-time PCR and Western blot.Results There was no statistical significant difference in the gene expression and protein level of SHBG and caspase-3 in group Ⅰ,Ⅱ and Ⅲ (P >0.05).In Ⅳ,Ⅴ and Ⅵ group,there was no statistical significant difference in the expression level of SHBG and caspase 3 (P >0.05).Compared with group Ⅰ,Ⅱ and Ⅲ,the a-mount of SHBG gene expression decreased obviously,the caspase-3 mRNA and protein level increased obviously and the trophoblast cell ap-optosis increased markedly (P <0.05).Conclusion Through siRNA interference technology can reduce SHBG gene expression in human trophoblastic cells,and it can lead to excessive apoptosis of human trophoblasts cells.
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BACKGROUND:Single fracture or colapse of the posterolateral tibial plateau fractures is relatively rare in the clinical work. Rational choice of surgical approach and internal fixation for posterolateral plateau fracture is significant to restore the lower limb force line, maintain the joint stability and obtain good biocompatibility. OBJECTIVE:To compare the stability and biocompatibility of Carlson posterolateral and posterior midline approaches for the treatment of posterolateral tibial plateau fractures with “T” shaped locking plate. METHODS:From July 2011 to July 2014, 43 patients with posterolateral tibial plateau fractures, who were treated in the Affiliated Hospital of Jining Medical University, were retrospectively analyzed. Al patients were assigned to two groups according to approaches. In the Carlson posterolateral approach group, 22 cases received “T”-shaped plate insertion by Carlson posterolateral approach. In the posterior midline approach group, 21 cases received “T”-shaped plate insertion by posterior midline approach. After repair, perioperative data, fixation effects and knee function score were compared and analyzed between both groups. RESULTS AND CONCLUSION:(1) 43 cases (43 knees) of posterolateral tibial plateau fractures were folowed up strictly. (2) No significant difference in operation time, fracture healing time, total load time, Hospital for Special Surgery score at 12 months postoperatively, tibial plateau angle and posterior slope angle immediately and 12 months postoperatively was detected between both groups (P > 0.05). (3) Significant differences in fracture exposure, blood loss, and excelent and good rate of Rasmussen at 12 months postoperatively were identified in both groups. Moreover, above indexes were better in the Carlson posterolateral approach group than in the posterior midline approach group (P< 0.05). (4) These findings confirmed that for a single fracture or colapse of the posterolateral tibial plateau fractures, two kinds of surgical approaches can achieve ful and direct exposure. Carlson posterolateral approach has good repair effect, fixation effect and biocompatibility.
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Objecive To evaluate the clinic value of 320 rows spiral CT in diagnosis of rib fractures. Methods Eighty-six patients with rib fractures were examined by 320 rows spiral CT. After the scanning, rib three-dimensional reconstructions were carried out. The number of ribs fractures was compared with that demonstrated by X-ray and common spiral CT. Results All patients were examined successfully in 3~5 seconds. The images quality of ribs reconstructed by the new method was excellent and exquisite. Many linear fractures and depressed fractures and costobrachial fractures which were not displayed in the images reconstructed by common spiral CT were displayed. The difference was significant statistically. Conclusion Compared with common spiral CT, 320 rows spiral is superior, with faster scanning speed, lower radiological dose and better image quality, improving the diagnostic accuracy of rib fractures to some extent. Therefore, it is an advanced and reliable diagnostic tool for rib fractures.
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BACKGROUND:Absorbable colagen membrane can be theoreticaly applied to secondary alveolar bone grafting in alveolar cleft surgery, which can improve the bone preservation and slow bone resorption. However, there is stil no unified conclusion. OBJECTIVE:To assess the efficacy and safety of absorbable colagen membrane for secondary alveolar bone grafting viaa systematic review. METHODS:MEDLINE, EMBASE, CBM and CAJD were searched for eligible articles addressing clinical randomized controled or controled trials of absorbable colagen membrane for secondary alveolar bone grafting. Test group received bone grafting with absorbable colagen membrane and control group only received bone grafting. Meta-analysis on the clinical success rate of bone grafting and incidence of complications in the recipient region was delivered with Revman 5.3. RESULTS AND CONCLUSION:Five clinical trials, involving 416 cleft sites and 387 participants, were included. Two had high risk of bias and the rest had unclear risk of bias. If “the height of new bone is≥ 50% of alveolar height” was adopted as clinical success, the clinical success rate of the test group was significantly higher than that of the control group (P=0.002, relative risk value=1.33, 95% confidence interval [1.11, 1.60]). If “the height of new bone is≥ 75% of alveolar height” was chosen as clinical success, the clinical success rate of the test group was higher than that of the control group, but there was no significant difference between the two groups (P=0.06, relative risk value=1.40, 95% confidence interval [0.99, 1.99]). For safety, the use of absorbable colagen membrane could not increase the complications incidence (P=0.35, relative risk value=0.66, 95% confidence interval [0.28, 1.58]). So, the use of absorbable colagen membrane is safe to improve the clinical success rate of secondary alveolar bone grafting in alveolar cleft surgery. More randomized controled trials should be considered to reinforce the conclusion.
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Objective Getting the robust exogenous gene expression vector under the control of porcine insulin promoter, and to lay the foundation for pancreaticβ-cells specific transgene expressing pigs.Method Using porcine insu-lin promoter ( PIP, 1500 bp of the 5′UTR from the porcine INS gene including the first exon and the first intron) to con-struct expression vector, the HindIII restriction site which connected the sequences of PIP and EGFP was designed before ATG, named PIP-HindIII-EGFP.Considering that the different location of restriction site may affect the expression efficien-cy of the transgene, we optimized the expression vector.Firstly the HindIII restriction site was deleted to realize the seam-less connection of PIP and EGFP,the vector was named PIP-EGFP.Also we mutated the 3′intron splicing acceptor site( SA) of the first intron into HindIII restriction site, named as PIP-SA( M)-EGFP.Three different EGFP expression vectors were respectively transfected MIN-6 mouse pancreatic β-cells, pig ear fibroblasts and kidney cells.The transfected cells were cultured for 48 h and harvested for RT-PCR, flow cytometry and Western blot analysis, to analyze and compare the expres-sion efficiency of vectors.Results After transfection,green fluorescence was observed only in MIN-6 mouse pancreaticβ-cells.RT-PCR analysis and product sequencing showed that the three expression vectors did have different stability with in-tron splicing.The PIP-HindIII-EGFP construct and PIP-EGFP vector produced two kinds of mRNA with the first intron spliced and no spliced, indicating the instability of intron splicing.Mutation of the PIP splice site would cause the first in-tron not spliced, while flow cytometry and Western blot displayed that the mutation induced a most efficient expression of the downstream gene.Conclusions A robust and specific β-cells expression vector has been successfully generated by mutating the intron splicing acceptor site of the porcine insulin promoter.It provides the foundation for preparation of pigs with pancreaticβ-cells specifically expressing the transgene.
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<p><b>OBJECTIVE</b>To study the effect of hyperbaric oxygen (HBO) administered at different pressures and different exposure time on the differentiation of neural stem cells (NSCs) in vitro.</p><p><b>METHODS</b>The cerebral cortices from newborn rats (0-3 days old) were sterilely collected, digested, and centrifuged. After removal of the supernatant, the cells were re-suspended with DMEM/F12 medium containing B27, bFGF and EGF. The NSCs of 2-3 passages were randomly divided into seven groups: a control (untreated) and 6 HBO treatment groups that NSCs were subjected to HBO treatment of different pressures (1, 2 or 3 ATA) and different exposure time (30 or 60 minutes). The differentiated NSCs were examined by neuron-specific enolase (NSE) immunocytochemistry 24 hrs later. Percentage of NSE positive cells differentiated from NSCs was assessed by fluorescent microscopy.</p><p><b>RESULTS</b>The percentage of NSE positive cells differentiated from NSCs was the highest in the HBO 2ATA-60 min group (9.17+/-0.50%) (P<0.01), followed by the HBO 3ATA-60 min (7.89+/-0.62%), HBO 2ATA-30 min (6.72+/-0.76%), HBO 3ATA-30 min (6.08+/-0.57%), HBO 1ATA-60 min (5.45+/-0.52%), HBO 1ATA 30 min (3.85+/-0.44%) and control groups (3.72+/-0.88%). In addition to the HBO 1ATA-30 min group, the other HBO treatment groups had increased significantly percentage of NSE positive cells compared with the control group (P<0.01). Under the same pressure, the 60 min treatment groups had increased significantly percentage of NSE positive cells compared with the 30 min treatment groups (P<0.01).</p><p><b>CONCLUSIONS</b>HBO treatment (2 ATA, 60 minutes) produces a best effect in the differentiation of NSCs into neurons.</p>
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Animals , Rats , Animals, Newborn , Cell Differentiation , Hyperbaric Oxygenation , Neurons , Cell Biology , Pressure , Stem Cells , Cell Biology , Time FactorsABSTRACT
[Objective] To determine the effects and possible mechanism of the thrombin antagonist r-RGD-Hirudin (HIR) on ventricular arrhythmia(VA) after acute myocardial infarction (AMI). [Methods] Seventy adult male Sprague-Dawley rats were randomly subjected to the 10 groups according to duration of left coronary occlusion: HIR 0 min, HIR 5 rain, HIR 10 min, HIR 20 min, HIR 30 min, and normal saline(NS) 0 min, NS 5 min, NS 10 min, NS 20 min, NS 30 min; and the average of every group is 7 rats. Acute myocardial infarction was produced by the occlusion of the left anterior descending coronary artery, then the measurements of arrhythmia and infarction sizing by Evans blue were assessed as well as the expression of three isoforms of inositol 1,4,5-trisphosphate receptors (IP3Rs) mRNA in isehemic myocardium by reverse transeriptase polymerase chain reactions (RT-PCR). [Results] Compared with NS groups, the measurements of VA in HIR were reduced significantly in 5 to 20 minutes after AMI (P<0.05). The incidence of VA was all positive related to the expression of three isoforms of IP3Rs mRNA (P<0.01). Compared with NS groups, the expression of type2,inositol 1,4,5-trisphosphate receptor (IP3R2) mRNA at 10 min and type3, inositol 1,4,5-trisphosphate receptor mRNA (IP3R3) at 10 min and 20 min after AMI were significant decreased (P<0.05) in HIR groups. [Conclusion] The thrombin antagonist r-RGD-Hirudin exerts its myocardial protection against ventricular arrhythmia after acute myocardial infarction possible through IP3R2 and IP3R3 and not typel, inositol 1,4,5-trisphosphate receptor (IP3R1).
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<p><b>OBJECTIVE</b>To study the protective effects of multiple course hyperbaric oxygen (HBO) treatment against hypoxic-ischemic brain damage (HIBD) in neonatal rats when HBO treatment is delayed (96 hrs after the HIBD event).</p><p><b>METHODS</b>Eighty-eight 7-day-old Sprague-Dawley rat pups were randomly assigned to control, HIBD and HBO groups. The HBO group was subdivided into cohorts receiving treatment 2 h, 48 h and 96 h, respectively, after HIBD was induced. The three subgroups comprising different therapeutic windows were further randomly assigned to receive 1, 2 or 3 courses of HBO treatment ("HBO-1, -2 and -3 sub-groups"). HBO was administered once daily (2 ATA), a course lasting for seven days. There was an interval of three days between the courses. All pups were sacrificed at the end of HBO treatment (31 days after HIBD). TUNEL staining was used for testing neuronal apoptosis in the cortex and the CA1 of the hippocampus, and NSE staining was used to ascertain cortical neuronal population.</p><p><b>RESULTS</b>1.There were significantly more TUNEL positive cells in the HIBD group than in the control group; NSE positive cells were significantly lower than in controls (P<0.01). 2. With the more delayed therapeutic window, the effects of apoptosis inhibition and neuronal protection of a single course of HBO were gradually reduced. 3. With increasing courses of HBO treatment, the effects of apoptosis inhibition and neuronal protection of HBO increased gradually in rats receiving treatment 48 and 96 hrs after HIBD. In the HBO group receiving treatment 2 hrs after HIBD, the number of apoptotic cells and NSE positive cells were close to that of the control group after one course of HBO treatment.</p><p><b>CONCLUSIONS</b>One course of HBO administered within 2 hrs after HIBD can effectively inhibit neuron apoptosis and protect neurons. The effects of apoptosis inhibition and neuron protection of HBO can be increased through increasing the number of HBO treatment courses in neonatal rats with HIBD even if initiation of treatment is delayed after HIBD.</p>
Subject(s)
Animals , Female , Male , Rats , Animals, Newborn , Apoptosis , Hippocampus , Pathology , Hyperbaric Oxygenation , Hypoxia-Ischemia, Brain , Pathology , Therapeutics , Phosphopyruvate Hydratase , Blood , Rats, Sprague-DawleyABSTRACT
Objective To evaluate different expressions of high mobility group box 1(HMGB1)and receptor for advanced glycation end products(RAGE)in placentas and their relationship with preeclampsia.Methods Fifteen early-onset pre-eclaraptic women(early-onset pre-eclampsia group),22 late-onset pre-eclamptic women(late-onset pre-eclampsia group)and 12 normotensive women(control group)in the third trimester were recruited at the Shengjing Hospital of China Medical University from March 2006 to March 2007.The localization and levels of HMGB1 and RAGE in placentas of the three groups were detected by the strept avidin biotin-peroxidose method.Results (1)Immunoreactivities to HMGB1:positive immnnostaining for HMGB1 was observed in trophoblast,macrophages,decidual cells,vascular muscle cells,endothelial cells and placental mesenchymal cells in the placentas from the pre-eclamptic women,while a low level of immunoreactivities was observed in the placentas from healthy pregnancies;the staining was observed within both the nuclei and the cytoplasm,mainly in the cytoplasm.The cytotrophoblast,especially the nuclei was extensively positive for HMGB1 in early-onset pre-eclampsia. (2)Immunoreactivities to RAGE:positive immunostaining for HMGB1 was observed in syncytiotrophoblast,macrophages and endothelial cells in the placentas from the preeclamptic women,while a low level of immunoreactivities was observed in the placentas from healthy pregnancies:the staining was in the cytoplasm and(or)cell membrane.The trophoblast was extensively positive for RAGE in early-onset pre-eclampsia.(3)Positive rate of HMGB1 expression:the expression of HMGB1 in early-onset group(73%,11/15)and late-onset group(64%,14/22)was significantly higher than that in normal group(17%,2/12;P<0.05),but no significant difference was found in early-onset group and late-onset group(P>0.05).(4)Positive rate of RAGE expression:the expression of RAGE in early-onset group(80%,12/15)and late-onset group (82%,18/22)was significantly higher than that in normal group(25%,3/12;P<0.05),but no significant difference was found in early-onset group and late-onset group(P>0.05).Conclusions The increased expression of HMGB1 and RACE in the placenta may play an important role in the pathogenesis of pre-eclampsis.The different locations may be associated with the occurrence of different onset types of pre-eclampsia.
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The Met tyrosine kinase receptor is a widely expressed molecule, which mediates pleiotropic cellular responses following activation by its ligand, hepatocyte growth factor/scatter factor (HGF/SF). Previously, one of the authors identified an alternatively spliced form of Met (Met-SM) that lacked a single exon of a 47-amino-acid segment in the juxtamembrane domain. Here we report that Met-SM is a potent transforming gene in NIH3T3 mouse fibroblast cells. Met-SM-transfected NIH3T3 cells show stronger foci-forming activity than wild type-Met-transfected ones. In addition, Met-SM-transfected NIH3T3 cells form colonies in soft agar and are tumorigenic in athymic nu/nu mice. Furthermore, HGF/SF significantly increases the focus-forming activity of Met-SM comparing to wild type Met. The amount of protein and of tyrosine kinase activity of Met-SM accumulates to a high level following HGF/SF treatment. The accumulation of Met-SM correlated well with its delayed ubiquitination and increased stability. These results are consistent with the important role of the juxtamembrane domain in protein stability of Met receptor and suggest that the alternatively-spliced form may contribute to the development and progression of human cancer.
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Mice , Female , Animals , Proto-Oncogene Proteins c-met/metabolism , Protein Isoforms/metabolism , NIH 3T3 Cells , Mutant Proteins/metabolism , Mice, Nude , Hepatocyte Growth Factor/pharmacology , Down-Regulation , Carcinogens/metabolism , Carcinogenicity Tests , Alternative SplicingABSTRACT
<p><b>OBJECTIVE</b>To investigate the influence of ACE inhibitor (perindopril) on the contractility and calcium transient and calcium handling proteins in ventricular myocytes from rats with experimental heart failure.</p><p><b>METHODS</b>Male Wistar rats were randomized to heart failure group treated with perindopril (CHF-T, 3 mg.kg(-1).d(-1)), heart failure group without treatment (CHF-C) and sham-operated group (PS) after heart failure was induced by constricting abdominal aorta for 16 weeks. All groups were further followed up for 12 weeks. Left ventricular myocytes were isolated, and single cell shortening fraction and [Ca(2+)](i) were simultaneously measured through laser scanning confocal microscope under the field stimulation (1.0 Hz). RT-PCR and Western blot were performed to evaluate the level of mRNA and protein of Na(+)-Ca(2+) exchanger (NCX(1)), sarcoplasmic Ca(2+)-ATPase (SERCA(2)) and phospholamban (PLB).</p><p><b>RESULTS</b>The fraction of cell shortening (FS%) and [Ca(2+)](i max) (nmol/L) were significantly smaller in group CHF-C than group PS (FS%: 7.51 +/- 1.15 vs 13.21 +/- 1.49; [Ca(2+)](i max): 330.85 +/- 50.05 vs 498.16 +/- 14.07; both P < 0.01). And in CHF-T group, FS and [Ca(2+)](i max) were greater than those in CHF-C group. In CHF-C group, the left ventricular mRNA of NCX(1) and PLB were significantly higher than those in PS group (R(NCX)(1)/beta-Actin: 0.51 +/- 0.12 vs 0.19 +/- 0.06, P < 0.01; R(PLB)/beta-Actin: 0.26 +/- 0.12 vs 0.20 +/- 0.08, P = 0.045), yet SERCA(2) mRNA was lower than PS group (0.48 +/- 0.10 vs 0.80 +/- 0.11, P < 0.01). In CHF-T group, the mRNA levels of NCX(1) and SERCA(2) were just in the midst of the CHF-C and PS group, and had statistical significance respectively (all P < 0.05). In CHF - C and CHF - T group, the protein levels of NCX(1) were 1.141 +/- 0.047 and 1.074 +/- 0.081 times PS group, respectively (both P < 0.05), and SERCA(2) protein levels were respectively 0.803 +/- 0.100 and 0.893 +/- 0.084 times as high as in PS group (both P < 0.05). The protein expression of NCX(1) and SERCA(2) were also different between CHF-C and CHF-T groups (both P < 0.05).</p><p><b>CONCLUSION</b>ACE inhibitor could improve cardiac function in CHF through directly enhancing the contractility of single myocardial cell, and these effects were probably mediated by its role in preventing the deleterious changes of calcium transient and calcium handling proteins in CHF.</p>