Objective To investigate the expression and significance of COX-2 and VECF in NHL Methods The expression of COX-2 and VECF in 28 cases of NHL was detected by immunohistochemistry, and 22 patients with benign lymphadenopathy were chosen as controls. Results Positive rates of COX-2 and VEGF were 82.1 %(23/28) and 78.6 %(22/28) in NHL respectively, significantly higher than that in the control (P <0.01). The expression rate of COX-2 was positively correlated with that of VEGF in tissues of NHL (χ~2 =10.50, P<0.01). Conclusion The expression of COX-2 and VEGF are high in NHL COX-2 and VEGF might have a common induction pathway, and selective COX-2 inhibitor might be a new drug for treatment of NHL in the future.

Objective To determine the incidence and effect of unrecognized cardiac injury in critically ill patients and evaluate the significance of elevations of serum troponin Ⅰ and APACHE Ⅱscore in patients with critically illness.Methods We measured the level of serum troponin Ⅰ and evaluated relationship between elevations of serum troponin Ⅰ and APACHE Ⅱ score,myocardial injury,mechanical ventilation,intensive care unit stay by means of retrospective chart review and analysis of clinical data.Results Thirty-four(21.4%)of the 159 patients had evidence of myocardial injury based on elevated levels of cardiac troponin Ⅰ,only 9(26.5%)of these 34 patients were diagnosed as having acute myocardial infaction by the intensive care unit staff.Mortality in patients with myocardial injury that was unrecogniazed(41.2%)or recognized(44.4%)was higher than in those without myocardial injury(16.0%)(P

ObjectiveTo explore the effects and possible mechanisms of VCR combined with low dose cyclophosphamide(CTX) intermittently to treat severe systemic lupus erythematosus(SLE).It is assumed that this might be a new combination therapy for SLE and expected to improve the overall prognosis and outcome of SLE.MethodsMurine chronic graft-versus-host disease(cGVHD) model were developed for study.They were randomly divided into the control group,vincristine (VCR) pulse therapy group,CTX pulse therapy group,CTX every other day(EOD) group,VCR+CTX combination group.One way ANOVA and repeated measure variance analysis were used for statistical analysis.Results① Six weeks after cGVHD models were set up,the average 24-hour urine protein quantification was(5.02±0.88) mg,anti-dsDNA antibody was positive,and Ⅳ LN pathology could be observed histologically in the model murine.So cGVHD models were successfully developed.② Significantly difference in decreasing of 24-hour urine protein quantification was found in the CTX EOD group,VCR+CTX combination group and other groups (P＜0.01).Significant decrease in Cr,ALT,anti-dsDNA,was found in the CTX EOD group,VCR+CTX combination group,CTX pulse therapy group and other groups(P＜0.05).Decrease in urine MCP-1 and TGF-β1 could be detected,and statistical significant difference in these parameters could be found in the CTX EOD group,CTX pulse therapy group,VCR+CTX combination group and other groups (P＜0.01).MCP-1 and TGF-β1'expression in model kidney were reduced in the CTX EOD group,VCR+CTX combination group and had statistical significant difference in the CTX EOD group,VCR+CTX combination group,VCR pulse therapy group,and CTX pulse therapy group.③ VCRand CTX combination treatment was effectivein 24-hour urine protein quantification,blood Cr,ALT,anti-dsDNA and urine MCP-1,as well as urine TGF-β1 (P＜0.05).Conclusion ① The combination of VCR and CTX is synergistic in decreasing 24-hour urine protein quantification,Cr,and the expression of MCP-1,TGF-β1.② The adverse effect of VCR+CTX combination group is similar to VCR pulse therapy group and CTX pulse therapy group.

Objective To investigate the effect of recruitment maneuver (RM) on acute respiratory distress syndrome (ARDS).Methods A total of 7 patients with early ARDS were involved in this investigate with pressure-control ventilation of FiO2 =1.Hemodynamics and extravascular lung water index (EVLWI) were monitored.After airway preparation,the ventilation parameters were adjusted to inspiration pressure (Pi) =24 cm H2O,positive end-expiratory pressure (PEEP) =10 cm H2O,frequency (f) =50,inspiration/expiration (I/E) =5/1.Up regulated PEEP to 24 cm H2O and Pi to 45 cm H2O for 3 respiration cycles.Then down regulated Pi to 30 cm H2O and had the artery blood gas analysis immediately.If PaO2 ＜ 450 mm Hg,Pi was increased 5 cm H2O above the last one,until PaO2 ＞ 450 mm Hg,which was considered RM success.Then PEEP was decreased 2 cm H2O and repeated the cycle as formers until PaO2 ＜350 mm Hg.The optimal PEEP was 2cm H2O above that.Maintained this airway pressure at least for 4 hours.Artery blood gas and hemodynamics of pre-and post-RM were monitored.The RM would be stopped by any unstable hemodynamic.Results In 6 of 7 patients,PaO2 and PEEP were higher than the baseline (P ＜ 0.01) after 4 hours of RM ; EVLWI decreased (P ＜ 0.01).RM was stopped in 1 patient,because of the unstable hemodynamic.None of the 7 patients got RM complications ; meanwhile,6 patients were cured.Conclusions Applying RM on ARDS is safe and effective.

Objective To evaluate clinical treatment method and efficacy of newly diagnosed acute promyelocytic leukemia (APL),and analyze the relevant factors about the long-term survival.Methods The clinical data of 48 patients with newly diagnosed APL were analyzed retrospectively.All of them used alltrans retinoic acid (ATRA) combined with anthracycline as induction remission therapy.After induction remission,ATRA combined with chemotherapy was used as consolidation therapy,and ATRA,arsenic trioxide and conventional chemotherapy alternated as maintenance therapy.Short-term efficacy was analyzed.Patients were followed up,and the rates of overall survival (OS) and disease-free survival (DFS) were analyzed.Long-term efficacy was analyzed by COX proportional hazards regression models univariate analysis.Results The complete remission (CR) rate was 87.5％(42/48) in all 48 patients with APL.The time from treatment beginning to CR was (30.7 ± 4.6) d.Age was the only factor affecting the rate of CR.The rates of 1-year,3-year and 5-year OS were (87.5 ± 4.8)％,(85.4 ± 5.1)％ and (78.3 ± 6.7)％ in 48 patients with APL.The rates of 1-year,3-year and 5-year DFS were (97.6 ±2.4)％,(93.9 ±4.2)％ and (89.5 ± 5.9)％ in 42 patients with CR.COX proportional hazards regression model univariate analysis result showed that the patient' s age,gender,lactate dehydrogenase,diffuse intravascular clotting,risk stratification and bone marrow abnormalities promyelocyte ratio had no correlation with the rate of DFS (P ＞0.05).Conclusions ATRA combined with anthracycline as induction remission therapy,after induction remission ATRA combined with chemotherapy as consolidation therapy,and ATRA,arsenic trioxide and conventional chemotherapy alternated as maintenance therapy can get a higher rate of CR and long-term survival in patients with newly diagnosed APL.It is worthy of clinical application.

ObjectiveTo examine whether Shenfu injection (SFI) reduces post-resuscitation myocardial dysfunction in a pig model by modulating expression imbalance of transcription factors of regulatory T cell, namely GATA-3 and T-bet.Methods Thirty pigs were randomly divided into sham group (n = 6) and cardiopulmonary resuscitation (CPR) group (n = 24) according to the random number table method, and the pigs in the CPR group were randomly subdivided into normal saline (NS) group, epinephrine (EP) group, and SFI group (n = 8 per group). After 8minutes of untreated ventricular fibrillation (VF) followed by 2 minutes of CPR, animals in three groups respectively received central venous injection of either 20 mL SFI (1.0 mL/kg, SFI group), EP (0.02 mg/kg, EP group) or NS (NS group). Blood samples were obtained before VF and 0.5, 2, 6 hours after restoration of spontaneous circulation (ROSC), and the parameters of hemodynamics and oxygen metabolism were determined. Surviving pigs were sacrificed at 24 hours after ROSC, the pathological changes in myocardium were observed, the levels of interleukin-4 (IL-4), tumor necrosis factor-α (TNF-α) andγ-interferon (IFN-γ) were measured by enzyme linked immunosorbent assay (ELISA), and expressions of protein and mRNA of GATA-3 and T-bet were determined by Western Blot and quantitative real-time polymerase chain reaction (RT-qPCR), respectively.Results Six pigs of three resuscitation groups were successfully resuscitated. The CPR time, number of defibrillation, defibrillation energy, and ROSC time were significantly decreased in the EP and SFI groups compared with those in the NS group. Compared with the sham group, the parameters of left ventricular systolic function and oxygen metabolism were significantly decreased, myofibril organelles were extensively damaged, and progressive and severe deterioration of the myocardium was found, and mitochondrial structure was not recognizable in the NS group; the level of IL-4 in myocardium were markedly decreased, while that of TNF-α, IFN-γand IFN-γ/ IL-4 [reflecting helper T cell 1/2 (Th1/Th2)] were significantly increased. Protein and mRNA expressions of GATA-3 were markedly reduced in the myocardium of pigs in the NS group compared with that of the sham group at 24 hours after ROSC, while T-bet was significantly increased. Compared with the NS group, animals treated with SFI had minimal myocardial intracellular damage, with decreased heart rate (HR, bpm: 90.33±3.79 vs. 106.83±5.36) and increased mean arterial pressure (MAP), cardiac output (CO), oxygen delivery (DO2), and oxygen consumption (VO2) at 6 hours after ROSC [MAP (mmHg, 1 mmHg = 0.133 kPa): 107.67±1.96 vs. 86.83±1.85, CO (L/min): 2.47±0.08 vs. 2.09±0.04, DO2 (mL/min): 364.31±4.21 vs. 272.33±3.29, VO2 (mL/min): 95.00±2.22 vs. 82.50±2.28, allP<0.05]. Compared with the NS groups at 24 hours after ROSC, level of IL-4 was markedly increased in myocardial cells (ng/L: 33.80±3.06 vs. 16.15±1.34,P< 0.05), while the levels of TNF-α, IFN-γ and IFN-γ/IL-4 were lowered significantly [TNF-α (ng/L): 18.16±0.71 vs. 29.64±1.89, IFN-γ (ng/L): 373.75±18.36 vs. 512.86±27.86, IFN-γ/IL-4: 16.15±1.34 vs. 33.80±3.06, allP< 0.05], and myocardial T-bet protein and mRNA expressions were reduced [T-bet protein (gray value): 0.41±0.07 vs. 0.59±0.11, T-bet mRNA (2-ΔΔCt): 4.37±0.21 vs. 7.57±0.55, bothP< 0.05], furthermore, myocardial GATA-3 protein and mRNA expressions were significantly up-regulated in SFI group [GATA-3 protein (gray value): 0.25±0.07 vs. 0.16±0.07, GATA-3 mRNA (2-ΔΔCt): 0.63±0.07 vs. 0.34±0.05, bothP< 0.05]. The parameters in SFI group were significantly improved compared with those of the EP group.ConclusionsMyocardial immune dysfunction is induced by Th1/Th2 imbalance following myocardial injury subsequent to CPR in pigs. SFI can attenuate myocardial injury and regulate myocardial immune disorders, protect post-resuscitation myocardial injury by modulating expression imbalance of transcription factors GATA-3 and T-bet.

Objective To investigate the effect of combination therapy by observing the salivary glands function and related organ pathology after given methotrexate (MTX) and cyclophosphamide (CTX) intermittently in induced mice model of Sjogren's syndrome (SS). To further explore the synergistic effect of combination therapy by detecting the immunological regulatory factor B cell activation factor belonging to the TNF family (BAFF) expression. Methods The ingredients of Lewis rat's exocrine glands homogenate were injected into female C57BL/6 mice to set up the mice model of SS. After established the SS mice model successfully, they were randomly divided into six SS model group, including low-dose MTX treatment group (0.02 mg/w), high-dose MTX treatment group (0.06 mg/w), CTX pause treatment group (1.2 mg/3 w), CTX alternate day treatment group (0.6 mg/2 d), MTX+CTX combination treatment group (MTX 0.02 mg/3 w+ CTX 1.2 mg/3 w). Treatment effects were assessed both clinically and histologically. Results Eighteen weeks after the first treatment, the improvement of the salivary secretion of the CTX alternate day treatment group and MTX+CTX combination treatment group were higher than other groups, which showed statistically significant difference (P<0.01). Compared with the SS model control group, HE staining showed that the lymphocytic infiltration of exoerine glands was decreased in the treatment group. In the CTX alternate day treatment group and MTX+CTX combination treatment group, few amount of inflammatory cell infiltration were found, and the expression intensity of BAFF mRNA and protein were decreased markedly in salivary gland than others by RT-PCR and immunohistochemistry assay (P<0.01). Conclusion MTX and CTX can inhibit lymphocytic infiltration of the salivary glands, inhibit BAFF transcriptional level and production of BAFF protein, leading to an increase of fluid production. It suggests that modulation of signaling via BAFF pathways may be a mechanism of action. MTX and CTX combination therapy is more effective than single-agent therapy. The inhibitory effects of MTX and CTX on BAFF-mediated inflammatory pathways are primarily synergistic.

Objective To confirm whether in post-resuscitation myocardial dysfunction involved in myocyte apoptosis mechanism in porcine model of cardiac arrest and apoptosis index varied from different modalities of cardiopulmonary resuscitation or not.Methods A total of 22 WZSP inbred small swine were randomly (random number) divided into sham operation group (SHAM) (n =6),defibrillation first group (DF,n =8) and chest compression first group (CF,n =8).Eight minutes after ventricular fibrillation was set up,standard CPR was carried out subsequently after defibrillation in porcine models of cardiac arrest in DF group and defibrillation after standard CPR in CF group,and hemodynamics were monitored.Twentyfour hours after restoration of spontaneous circulation (ROSC),animals were sacrificed,and myocardial specimens were examined with electron microscopy,Western blot,quantitative RT-PCR,and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.The experimental data were analyzed by SPSS 17.0.Student's t test was employed for comparisons between two groups.Differences within groups at different time intervals were compared with repeated measures ANOVA.A two-tailed value of P ＜ 0.05 was considered statistically significant.Results Myocardial function was significantly impaired after ROSC.Levels of Bcl-2,Bax and caspase-3 protein was markedly increased in the CF and DF groups than those in the SHAM group (P ＜ 0.05) at 24 h after ROSC,while Bcl-2/Bax was significantly reduced in the CF and DF group compared with the SHAM group (P ＜ 0.05),and much more apoptotic cells were observed in cardiac arrest animals in comparison with sham-operation animals (P ＜ 0.05).Six hours after ROSC,hemodynamic indicators improved significantly in group DF than those in group CF,but Bcl-2,Bax and caspase-3 protein levels and apoptotic index were not significantly different bewteen the DF group and CF group (P ＞ 0.05).Conclusions Caspase-3-mediated apoptosis might be one of the main pathological mechanisms of postresuscitation myocardial injury in a porcine model of cardiac arrest,but there was no statistically significant difference in apoptosis index between two resuscitation modalities,showing no one modality was superior over another.

ObjectiveTo study the inhibiting effects on the invasion and metastasis of melanoma by CXCR4 gene silence in nude mice.MethodsThe CXCR4 specific recombinant plasmid vector was constructed and transfected into the cultured MV3 cell line with lipofectamine.The models of subcutaneous melanoma in nude mice were established with MV3 cells.The nude mouse model of lung metastasis was established by injection of MV3 cells into the tail vein.The animals were sacrificed at 8weeks after the melanoma cells injection.CXCR4-shRNA plasmid vectors were discontinuously injected directly into the established tumor and vein.The changes of weight and size of the tumors and the mice body weight during the therapy were calculated respectively.Histological observation was performed to evaluate the presence and number of metastatic tumors.ResultsThe subcutaneous melanoma tumors in nude mice were established successfully.The growth of tumors in the CXCR4-shRNA injected nude mice was inhibitted obviously through tumor growth curve. There were significant differences between negative shRNA control nude mice and blank control nude mice (P＜0.01).Melanoma cells with CXCR4 shRNA permanent transfection had a much lower lung and brain and liver metastatic potential in nude mice than control cells and mock control cells in vivo.ConclusionsCXCR4 gene silencing mediated by shRNA significantly suppresses the growth of MV3 cell in vitro.Silencing of CXCR4 mediated by shRNA can also effectively decrease the metastatic potential of lung and liver and brain.

Objective To investigate the predictive value of Alberta stroke program early CT score on diffusion-w eighted imaging (DWI-ASPECTS) for predicting new cerebral microbleeds (CMBs) in patients w ith acute middle cerebral artery infarction. Methods The patients w ith acute middle cerebra artery infarction w ere enroled prospectively. MRI examinations w ere completed w ithin 48 h on admission and they w ere examined again at 10 to 14 d after onset. Susceptibility-w eighted imaging (SWI) w as use to detect
CMBs. DWI-ASPECTS w as used to assess the infarction extent. Results A total of 82 patients w ith acute middle cerebra artery infarction w ere enroled, including 27 females and 55 females. Their ages w ere 71.7 ± 8.9 years. Eighteen patients (22.0%) had old CMBs, 25 (30.5%) had new CMBs, 57 (69.5%) did not have new CMBs. Compared w ith the non-new CMB group, DWI-SPECTS (3.20 ±1.73 vs.7.11 ±1.69;t = 9.573, P <0.001) w as low er, NIHSS scores (16.20 ±4.06 vs.12.63 ±5.06; t = 3.111, P = 0.003) w ere higher, there w ere more patients w ith atrial fibrilation ( 40.0% vs.15.8%; χ2 = 5.722, P = 0.017), proportion of intensive antiplatelet therapy ( 0% vs.28.1%; P = 0.002) w as low er, there w ere more large artery atherosclerosis type ( 60.0% vs.29.8%; χ2 = 6.650, P = 0.010 ), more cardiogenic cerebral embolism type (36.0% vs.5.3%; P = 0.001), and less smal artery occlusion type ( 0% vs.57.9%; P <0.001) in the new CMB group, and there w ere no statistical differences in the other indexes. Multivariate logistic regression analysis show ed that after adjusting age, sex, alcohol, histories of hypertension, hyperlipidemia, diabetes, atrial fibrilation and previous stroke or transient ischemic attack history, the higher the DWI-ASPECT scores ( > 5), the risk of new CMBs w ould decrease 86 % (odds ratio 0.14, 95%confidence interval 0.17 -0.48; P < 0.001). Receiver operating characteristic curve analysis show ed that the sensitivity of prediction of DWI-ASPECTS ≤5 for the new CMBs w as 87.7%, specificity w as 88.3%, and the area under the curve w as 0.940. Conclusions DWI-ASPECTS can effectively predict the new CMBs in patients w ith acute middle cerebra artery infarction.