Probability Prediction in Multistate Survival Models for Patients with Chronic Myeloid Leukaemia

In order to find an appropriate model suitable for a multistate survival experiment, 634 patients with chronic myeloid leukaemia (CML) were selected to illustrate the method of analysis.After transplantation, there were 4 possible situations for a patient: disease free, relapse but still alive, death before relapse, and death after relapse. The last 3 events were considered as treatment failure. The results showed that the risk of death before relapse was higher than that of the relapse,especially in the first year after transplantation with competing-risk method. The result of patients with relapse time less than 12 months was much poor by the Kaplan-Meier method. And the multistate survival models were developed, which were detailed and informative based on the analysis of competing risks and Kaplan-Meier analysis. With the multistate survival models, a further analysis on conditional probability was made for patients who were disease free and still alive at month 12 after transplantation. It was concluded that it was possible for an individual patient to predict the 4 possible probabilities at any time. Also the prognoses for relapse either death or not and death either before or after relapse may be given. Furthermore, the conditional probabilities for patients who were disease free and still alive in a given time after transplantation can be predicted.     

Construction, Expression and In Vitro Biological Behaviors of Ig scFv Fragment in Patients with Chronic B Cell Leukemia

The clonotypic surface Ig receptor(SmIg)ex-pressed by malignant Bcells,idiotype,is a tumor-specific antigen and an attractive target for activei mmunotherapy.This kind of SmIg can be pro-cessed and presentedinthe context of MHCclass Iand classⅡmolecules onthe surface of the tumor.It has been shown that Id vaccination inducestumor-specific T cell responses in patients with Bcell malignancies.Such antigenic epitopes mayserve as candidates for novel peptide-vaccine strat-egies,and as tools …     

Expression of CD40 and CD40L on Peripheral Blood Mononuclear Cells in Patients with Condyloma Acuminatum

The initiation,development and transforma-tion of condyloma acuminatum(CA)bear a closerelation to the cellular i mmune function ofhost[1-3].The CD40and CD40ligands,a couple ofi mportant costi mulatory molecules of the specifici mmune systemin vivo,play an i mportant role inthe activation of Tlymphocytes and the secretionof effective cytokines.To obtaintheinformation a-bout the expression level and explore the clinicalsignificance of CD40and CD40L on peripheralblood mononuclear cells(PMBC…     

Correlation between Cyclin A Gene Expression in Adult Patients with Acute Leukemia and Drug Resistance

Adultacuteleukemia (AL)isoneofthemostcommonmalignanttumorsofhematology .Withtherecentprogressinchemotherapyandsupportivether apy ,theremissionandsurvivalrateinALhavebeenmarkedlyimproved .However ,drugresistanceandrelapsearestillimportantfactorsaffectinglongsur vivalofthese patients .Theabnormalregulationofcellcycleisanotherfactorthatcannotbeignoredex ceptformultipledrugresistance (MDR) .WedetectcyclinA ,multidrugresistantgene (mdrl) ,topoiso meraseⅡα(TopⅡα)andbcl 2inadultpatientswithA…     

Expression and Significance of Toll-like Receptor 2, 4 of Peripheral Blood Mononuclear Cells in Acute Abdomen Patients Associated with Systemic Inflammatory Response Syndrome

The changes of Toll-like receptor (TLR) 2, 4 of peripheral blood mononuclear cells (PBMCs) in the acute abdomen patients associated with systemic inflammatory response syndrome (SIRS) and their potential significance were explored. A clinical study was performed on 103 acute abdomen patients in whom 65 were associated with SIRS. Forty healthy individuals served as normal controls. The mRNA expression of TLR2, 4 was detected by RT-PCR, and the expression of TNF-αand EL-6 by ELISA. The level of plasma endotoxin, hospital stay and mortality were measured. It was found that the endotoxin level was increased to varying degrees in all the acute abdomen patients, and the endotoxin level was and hospital stay longer in SIRS group than in non-SIRS group (P<0.01). TLR2 mRNA, TLR4 mRNA, IL-6 and TNF-αcould be detected with low value in normal controls, but they were up-regulated markedly on the 1st day after admission. Then TLR4 mRNA, IL-6 and TNF-αwere decreased gradually, but TLR2 mRNA maintained at a high level till the 5th day. These indexes above in SIRS group were higher than those in non-SIRS group (P<0.01). The results of correlation analysis revealed the expression of TLR2, 4 mRNA was positively correlated with the levels of TNF-αand IL-6, and the hospital stay. The results of Logistic regression demonstrated that over-expression of TLR2, 4 mRNA might result in higher risk of multiple organ dysfunction syndrome (MODS). It was concluded that in the acute abdomen patients associated with SIRS, the expression of TLR2, 4 in PBMCs was increased markedly, suggesting that TLR might play an important role in the pathogenesis of acute abdomen associated with SIRS.     

Expression of CD80／CD86 and CTLA-4 mRNA in Peripheral Blood Mononuclear Cells of the Patients with Systemic Lupus Erythematosus

The role of CD80/CD86 and CTLA-4 in the pathogenesis of systemic lupus erythematosus and their clinical significance was investigated. By using RT-PCR technique, the expression of CDS0/CD86 and CTLA-4 mRNA in peripheral blood mononuclear cells (PBMC) were semiquantitatively detected in 32 patients with active SLE. The results showed that the percentage of positive CD86 expression in active SLE was increased significantly as compared with normal controls (90.63% vs 60.00 %, P＜0.01). The mean level of CD86 mRNA expression in active SLE group was markedly higher than in the normal controls (0. 6410 0. 0174 vs 0. 4510 0. 0402, P＜0. 001).Compared with normal controls, the percentage of positive CTLA-4 expression and the mean level of CTLA-4 mRNA expression in active SLE group were both increased significantly (both P＜0.01). There was no statistical differences in positive rate of CDS0 and the average level of CDS0 mRNA between the two groups (both P~0.05). It was concluded that the aberrant expression of CD86 and CTLA-4 might play an important role in the activity and development of SLE.     

Changes of CD4＋ CD25＋ Regulatory T Cells in Peripheral Blood in Patients with Hepatocellular Carcinoma Before and after TACE

This study investigated the changes of CD4 CD25 regulatory T cells (Tregs) in periph-eral blood of patients with hepatocellular carcinoma before and after transcatheter arterial chemoem-bolization (TACE). The proportion of CD4 CD25 Tregs among CD4 T lymphocytes in peripheral blood of 33 patients with hepatocellular carcinoma was determined by flow cytometry before, 1 week and 1 month after TACE. And 25 healthy volunteers served as control. One month after TACE, the patients were divided into two groups: 22 in group A, who were in stable condition or getting better; and 10 in group B, who were deteriorating. One patient died and was excluded. The results showed that the percentage of CD4 CD25 Tregs among CD4 T lymphocytes did not significantly change in the 33 patients 1 week after TACE as compared with that before TACE, however, the difference was significant (P<0.01) between the patients with hepatocellular carcinoma and the healthy subjects. The percentage of CD4 CD25 Tregs among CD4 T lymphocytes in group A 1 month after TACE was decreased significantly in comparison with that before and 1 week after TACE (P<0.01), whereas, that in group B was increased significantly 1 month after TACE (P<0.01). It was concluded that patients with hepatocellular carcinoma had a higher proportion of CD4 CD25 Tregs in peripheral blood. TACE did not significantly affect the level of CD4 CD25 Tregs within short time (such as 1 week). The proportion of CD4 CD25 Tregs in peripheral blood 1 month after TACE was related to the prognosis of hepatocellular carcinoma.     

Changes of CD4＋ CD25＋ Regulatory T Cells in Peripheral Blood in Patients with Hepatocellular Carcinoma Before and after TACE

This study investigated the changes of CD4＋ CD25＋ regulatory T cells （Tregs） in periph-eral blood of patients with hepatocellular carcinoma before and after transcatheter arterial chemoem-bolization （TACE）. The proportion of CD4＋ CD25＋ Tregs among CD4＋ T lymphocytes in peripheral blood of 33 patients with hepatocellular carcinoma was determined by flow cytometry before, 1 week and 1 month after TACE. And 25 healthy volunteers served as control. One month after TACE, the patients were divided into two groups： 22 in group A, who were in stable condition or getting better; and 10 in group B, who were deteriorating. One patient died and was excluded. The results showed that the percentage of CD4＋CD25＋ Tregs among CD4＋ T lymphocytes did not significantly change in the 33 patients 1 week after TACE as compared with that before TACE, however, the difference was significant （P〈0.01） between the patients with hepatocellular carcinoma and the healthy subjects. The percentage of CD4＋ CD25＋ Tregs among CD4＋ T lymphocytes in group A 1 month after TACE was decreased significantly in comparison with that before and 1 week after TACE （P〈0.01）, whereas, that in group B was increased significantly 1 month after TACE （P〈0.01）. It was concluded that patients with hepatocellular carcinoma had a higher proportion of CD4＋CD25＋ Tregs in peripheral blood. TACE did not significantly affect the level of CD4＋ CD25＋ Tregs within short time （such as 1 week）. The proportion of CD4＋CD25＋ Tregs in peripheral blood 1 month after TACE was related to the prognosis of hepatocellular carcinoma.     

Analysis of CD4^＋CD25^＋ Regulatory T Cells and Foxp3 mRNA in the Peripheral Blood of Patients with Asthma

The changes of CD4 CD25 regulatory T cells (CD4 CD25 Treg) and Foxp3 mRNA in peripheral blood mononuclear cells (PBMCs) from patients with asthma were investigated in order to elucidate the possible roles of CD4 CD25 Treg in the development of asthma. The peripheral blood samples were collected from 29 healthy controls (normal control group) and 78 patients with asthma which included 30 patients in exacerbation group, 25 patients in persistent group, and 23 patients in remission group. By using flow cytometry and RT-PCR, the CD4 CD25 Treg ratio and Foxp3 mRNA in PBMCs were detected. The CD4 CD25 Treg ratio and Foxp3 mRNA in PBMCs of exac-erbation and persistent groups were lower than that of remission and normal control groups (P<0.05). Although the CD4 CD25 Treg ratio and Foxp3 mRNA of remission group were also lower than that of normal control group, there was no significant difference between them (P>0.05). As compared with persistent group, exacerbation group had lower CD4 CD25 Treg ratio and Foxp3 mRNA (P<0.05). It was indicated that the decrease of CD4 CD25 Treg ratio and its function in PBMCs may be responsible for pathogenesis of asthma.     

Redistribution of Platelet Membrane Glycoprotein IV and Release of Intracellular α-granule Thrombospondin in Patients with Chronic Myelogenous Leukemia

Plateletmembraneglycopr0tein(GP)IV,als0knownasGPIIIbandCD36,hasbeenproposedasthemembranerecept0rthrombospondin(TSP).TSPreleasedfromplateleta-granuleshasbeenshownt0playaroleinitsbindingt0GPlVonplateletmem-braneandtobecriticalfortheconsolidationofaggregatingplateletinthromb0sisandhem0stasis[lJ.Duringchronicmyelogenousleukemia(CML),plateletmernbraneGPsundergochangesintheirdistributions,sug-gestingqualitativeand/orquantitativeab-normalitiesandtherebyaffectingfunction0fplateletadhesionand…     

Changes of CD4^＋CD25^＋ Regulatory T Cells in Patients with Acute Coronary Syndrome and the Effects of Atorvastatin

The function of CD4＋CD25＋ regulatory T lymphocytes （Treg） in patients with acute coronary syndrome （ACS） and the effects of atorvastatin were investigated. Forty-eight patients with ACS were randomly divided into two groups： group C receiving conventional therapy （n=24）, and group C＋A receiving conventional therapy＋atorvastatin （10 mg/day, n=24）. T lymphocytes from ACS patients （before and 2 weeks after the treatment） or 18 healthy subjects were separated and the flow cytometry was used to measure the percentage of Treg. The inhibitory ability of Treg on effector T cells was determined by mixed lymphocyte reaction （MLR）. ELISA was used to measure the serum levels of cytokines （IL-10, TGF-β1 and IFN-γ） before and after treatment. The results showed that as compared with normal control group, Treg percentage was decreased significantly （P〈0.01）, the inhibitory ability of Treg on the T lymphocytes proliferation was reduced （P〈0.01）, IFN-γ levels were increased and IL-10 and TGF-β1 levels were lowered in ACS patients. After treatment with atorvastatin, Treg percentage and the inhibitory ability of Treg on T lymphocytes proliferation were significantly increased in ACS patients. Serum IFN-γ was decreased significantly, while IL-10 and TGF-β1 were elevated significantly as compared with the non-atorvastatin group. The number of Treg was positively correlated with serum TGF-β1, but negatively with serum IFN-γ and CRP. It was concluded that ACS was associated with decreased number and defected function of Treg, which may play an important role in initiating immune-inflammatory response in ACS. The inhibitory effects of atorvastatin on inflammation in ACS may be due to its beneficial effects on Treg and restoration of immune homeostasis.     

Cerebral Ischemic Tolerance Induced by 3-nitropropionic Acid Is Associated with Increased Expression of Erythropoietin in Rats

Preconditioning of brain tissues with sub-lethal stresses or stimuli can result in resistance to subsequent lethal ischemic events in a response called ischemic tolerance[1] [2—4] . Recently, it was reported that such a neuronal tolerance could be induced by irreversible inactivation of succinate dehydrogenase (SDH), which is a mitochondrial complex Ⅱ (Krebs cycle) enzyme. SDH is the main respiratory electron transfer pathway into the plastoquinone (PQ) pool and could limit the damage inf…     

Regulation of Insulin Secretion and Expression of SUR1 Gene by Chronic Exposure to Free Fatty Acids in Rat Pancreatic β Cells

Insulinresistanceandimpairedinsulinsecretionarethetwomainpathophysicologicalfeaturesoftype2diabetes .Continuinglossofβ cellfunctionistheunderlyingcauseofdeterioratingmetaboliccontrolinpatientswithtype 2diabetes .Fattyacidscouldplayaroleinthereductionofβ…     

TNF-α Up-regulates Matrix Metalloproteinase-9 Expression and Activity in Alveolar Macrophages from Patients with Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality throughout the world. Unbalance of proteinases and an-tiproteinases is thought to be important in the pathogene-sis of COPD, as well as inflammation and oxidative stress. However, neutrophil elastase is likely to be the major proteinase involved in lung destruction in alpha-1 antitrypsin deficiency, and it may not be involved in COPD caused by inhalational exposures. Matrix metal-loproteinases…     

The Expression of Interleukin-17, Interferon-gamma, and Macrophage Inflammatory Protein-3 Alpha mRNA in Patients with Psoriasis Vulgaris

Interleukin 17(IL 17)isanewlyidentifiedpro inflammatorycytokinethatisproducedbyactivatedTcells.IL 17hastheabilitytoinducestromacellstoproduceproinflammatorycytokinesandhematopoieticcytokines .Soitmayparticipateinsomeinflammatoryreactionsandsomeimmunoloreg…     

Expression of CD28 and CTLA4 on T Cells in Bone Morrow of Immune-mediated Aplastic Anemia Mice

Summary： To investigate the expression and significance of CD28 and CTLA4 on T cells in bone marrow of aplastic anemia （AA） mice, in vitro bone marrow mononuclear cells （BMMNCs） were activated through being incubated with PHA （15 μg/mL）. The expression of CD28 and CTLA4 on T cells incubated with or without PHA was detected by two-color flow cytometry. The expression of CD28 and CTLA4 was significantly increased after PHA stimulation. In the AA mice. the expression of CD28 with or without PHA stimulation was both higher than that in the normal mice （both P〈0.01）, but the expression of CTLA4 with or without PHA stimulation showed no significant difference in comparison to that in the normal mice （both P〉0.05）. In the AA mice, there were more activation and activated potential of T cells than the normal, and the abnormal expression of CD28 and CTLA4 may participate in immunological disorder mediated by T cells.     

Effect of Yiqi Huoxue（益气活血） Herbs on Vascular Endothelial Cells and Platelets in Patients with Chronic Cor Pulmonale

Objective: To observe the clinical effect of Yiqi Huoxue (益气活血, YQHX) herbs in treating the patients with chronic cor pulmonale and to explore its mechanism by determining the relationship of oxidation/antioxidation system and how such herbs change on the function of endothelial cells and platelets. Methods: Fifty-eight patients were divided into two groups: conventional therapy group (control group, 28 paventional management. The treated group were treated with YQHX 150 ml, twice a day, plus the conventional treatment, and the clinical efficacy was recorded. The lipid peroxidation (LPO), superoxide dismutase (SOD), α-granule membrane protein (GMP140), partial pressure of arterial oxygen (PaO2), partial pressure of carbon dioxide in artery (PaCO2) and circulating endothelial cells (CEC) were measured respectively before and after treatment, and the relationship between various parameters were analyzed. The results were compared with those of 10 healthy subjects got at the same period. Results: (1) The effective rate and PaO2 of the treated group was higher than that of the control group and there were no difference in PaCO2 between the two groups. (2) The levels of LPO, GMP140, CEC in all the patients before therapy were significantly higher than those of the healthy group, and there were marked decrease in the levels of those after treatment (all P＜0. 01). On the contrary, the levels of SOD in all the patients before therapy were markedly lower than those in the healthy subjects and increased after treatment, P＜0.01. (3) The increase of SOD in the treated group was significantly more obvious than that of the control group. In the treated group, the decrease of LPO, GMP140, CEC were markedly more obvious than those in the control group (all P＜0.01).(4) The number of CEC, as well as GMP140, was negatively correlated to PaO2 (P＜0.01) and SOD (P＜0.01), which was positively correlated to LPO (P＜0.01). There was a positive correlation between CEC and GMP140 (P＜0.05). Conclusion: YQHX herbs in treating chronic cor pulmonale proved to be effective by balancing the oxidation and antioxidation, protecting the pulmonary endothelial cells and activated platelets and helpful in treating respiratory failure.     

Effect of Tiotropium Bromide on Expression of CD_8~＋CD_（25）~＋FoxP_3~＋ Regulatory T Cells in Patients with Stable Chronic Obstructive Pulmonary Disease

The expression of CD8+CD25+FoxP3+ regulatory T cells(CD8+Tregs) in the peripheral blood of patients with stable chronic obstructive pulmonary disease(COPD),and the effect of muscarinic cholinergic receptor antagonist tiotropium bromide on the expression of CD8+Tregs were investigated.Twenty-three patients with moderate to severe stable COPD were enrolled in this study.All patients inhaled tiotropium bromide(18 μg daily) for 3 months.Before and after inhalation of tiotropium bromide,peripheral blood samples were collected from the patients,and T cells were labeled by three-color labeled monoclonal antibodies.Flow cytometry was used to detect the quantity and percentage of CD8+T cells,CD8+CD25+T cells,CD8+Tregs,CD4+T cells,CD4+CD25+T cells and CD4+CD25+FoxP3+ regulatory T cells(CD4+Tregs) respectively.The percentage of CD4+T cells was increased from(27.82±2.18)% to(35.53±1.3)%(t=3.20,P=0.004) in the peripheral blood of patients with stable COPD after inhalation of tiotropium bromide for 3 months,that of CD4+CD25+T cells was decreased from(10.03 ±1.42)% to(4.21 ±0.65)%(t=3.78,P=0.001),and that of CD8+Tregs was increased from(8.41 ±1.68)% to(21.34 ±4.20)%(t=2.72,P=0.013).At baseline,CD8+T cells,CD8+CD25+T cells and CD4+Tregs were detectable in the peripheral blood,but no significant changes were observed after treatment.Linear correlation analysis revealed that the difference before and after treatment in CD4+T cells and CD4+CD25+T cells was negatively correlated with the ratio of change in CD8+Tregs before and after treatment(r=-0.61,P=0.013;r=-0.72,P=0.001 respectively).In the peripheral blood of patients with stable COPD,there was the expression of CD8+Tregs and CD4+Tregs.Muscarinic receptor antagonist,tiotropium bromide,can promote the amplification of CD4+T cells,inhibit the expression of CD25+T cells,and enhance the expression of CD8+Tregs.CD8+Tregs and CD4+Tregs can be used as new indicators to understand the immune status of patients.They are helpful in judging the treatment efficacy and disease immunophenotype.