Objective To evaluate the effect and mechanism of rt-PA combined with high pressure oxygen (HPO)on cerebral ischemia-reperfusion injury in rats.Methods The model of cerebral ischemia-reperfusion injury was constructed by using middle cerebral artery occlusion.The neurological function score;brain index,water content and infarction volume;SOD;LDH;NOS;MDA;LD;NO and NOS were measured.The protein and mRNA expressions of iNOS,BDNF,p75NTR and TrkB were also detected by RT-PCR and Western blot to evaluate and compare the protective effect of rt-PA combined HPO therapy. Results rt-PA combined HPO could significantly decrease the neurological function score;brain index,water content,and infarction volume;SOD;NOS;MDA;LD;NO and NOS but increase LDH content and the weight of rats,compared with rt-PA.In addition,rt-PA combined HPO could increase BNDF and TrKB expressions and downregulate the expressions of iNOS and p75NTR,compared with rt-PA (P<0.05).Conclusion The rt-PA combined HPO therapy has a greater protective effect than rt-PA therapy and its mechanism might be related to having antioxidant effects, increasing the expressions of BDNF and TrKB,and decreasing the expressions of iNOS and p75NTR.

Objective To investigate the effects of 6-minutes of walking exercise (6-MWE) on the exercise tolerance and left ventricular diastolic function (LVDF) of heart failure patients with a normal ejection fraction (HFNEFs).Methods Ninety grade Ⅱ or Ⅲ HFNEFs of the New York heart association (NYHA) were randomly divided into an exercise training group and a control group with 45 cases in each.The control group was treated with routine drugs.The exercise training group was treated with the same drugs plus 6-MWE.Before and after the sixmonth period of treatment,plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were determined,each subject's left atrial volume index (LAVI) was measured with a color ultrasonic cardiogram (UCG),and their 6-minute walk distance (6-MWD) was measured.Results Plasma NT-proBNP levels and 6-MWD improved significantly comparing with before treatment in both groups.The average 6-MWD,LAVI and plasma NT-proBNP level all improved significantly more in the experimental group.Conclusion 6-MWE can significantly improve the exercise tolerance and LVDF of HFNEFs,and improve their quality of life.Walking can be helpful in delaying the development of HFNEF.

OBJECTIVETo detect the expression of cytokines by acute promyelocytic leukemia (APL) cells before and after exposure to arsenic trioxide.

METHODSDiagnoses were performed according to the FAB cytological classification criteria and cytogenetic criteria. Bone marrow or blood samples from APL patients were collected in heparinized tubes, then primary APL cells were separated by traditional Ficoll-Hypaque density centrifugation and purified after adherence to plastic surfaces. IL-1(beta), IL-6, IL-8, TNF alpha and G-CSF levels in the leukemia cell culture supernatants were detected by ELISA. At the same time, nitro blue tetrazolium (NBT) reduction test was used to detect the differentiation of APL cells.

RESULTSAfter 96 hours exposure to arsenic trioxide, 10 - 6 mol/L in vitro or 10 mg/d in vivo, APL cells showed a significant increase of IL-1(beta) (P < 0.05) and G-CSF (P < 0.05) production, and a significant decrease of IL-6 (P < 0.05) and IL-8 (P < 0.05). However, there was no obvious variation of TNF alpha when compared with APL cells without exposure to arsenic trioxide. On the other hand, the proliferation ratio of APL cells in vitro was statistically correlated to the IL-1(beta) secretion ratio or G-CSF secretion ratio. The cell number ratio in patients with detectable IL-1(beta) or G-CSF was higher than that without detectable IL-1(beta) or G-CSF.

CONCLUSIONIL-1(beta) and G-CSF secretion may play an important role in the proliferation of APL cells after exposure to arsenic trioxide.

Arsenicals ; pharmacology ; Cells, Cultured ; Cytokines ; secretion ; Granulocyte Colony-Stimulating Factor ; secretion ; Humans ; Interleukin-1 ; secretion ; Interleukin-6 ; secretion ; Interleukin-8 ; secretion ; Leukemia, Promyelocytic, Acute ; metabolism ; Oxides ; pharmacology ; Tumor Necrosis Factor-alpha ; secretion

Objective To establish new classification criteria for early rheumatoid arthritis (E-RA) based on large samples of early inflammatory arthritis patients and to evaluate the value of this criteria in China.Methods Patients who had arthritic complaints with disease duration less than one year were enrolled.They were divided into RA group and non-RA group according to the clinical diagnosis by experienced rheumatologists.The clinical and laboratory parameters were analyzed and those with high sensitivity or specificity were selected as the new classification criteria.Statistical analysis was carried out by using t test,x2 test and Logistic regression.Results ① A total of 803 patients with early inflammatory arthritis were included in this study.Five hundreds and fourteen patients were diagnosed as early RA and 251 were diagnosed as other rheumatic diseases,and the diagnosis of 38 patients remained unestablished by the end of follow-up.② New E-RA classification criteria were established based on the parameters with high sensitivity and/or specificity.The sensitivity of the new E-RA criteria was 84.4％,which was higher than 1987 ACR criteria (58.0％),while the corresponding specificities were similar,which were 87.4％ and 93.6％ respectively.③ Compared with the complex scoring system of 2010 ACR/EULAR criteria,the E-RA criteria was more simple and practical.The diagnostic sensitivity and specificity of E-RA criteria were higher than those of 2010 ACR/EULAR criteria reported in the literatures.④ New classification criteria based on scoring system using Logistic regression analysis was established.The sensitivity of this criteria was 86.4％,which was higher than 1987 ACR criteria (58.0％).Conclusion The diagnostic value of the E-RA criteria developed in this study for early RA is better than 1987 ACR criteria,and is more simple than 2010 ACR/EULAR criteria.It may be used as a new classification criteria for early RA diagnosis.

This study explores the effects of enhancing the definitive hematopoiesis(DH)signals during the differentiation of human embryonic stem cells(hESCs)into hematopoietic stem/progenitor cells on the generation efficiency and effector function of natural killer(NK)cells generated from hESCs(also known as hESC-NK cells).The hESC(H1)were transformed into embryoid bodies(Ebs)by centrifugation,and during the induction of K562,were used to analyze the efficiency of hematopoietic differentiation,the efficiency of NK cell generation from hESC,the in vitro effector functions,and the expression of effector function related surface receptors.Compared to the control group,the DH group had a significant increase in the number of arterial hematopoietic endothelial cells(CD34+DLL4+)and a significant decrease in primitive hematopoietic related cells(CD34-CD43+)on day 8 of hematopoietic differentiation(P<0.05).On day 28 of NK cell differentiation,the DH group demonstrated a significant increase in the number of NK cells(CD45+CD56+),while a slight increase in the expression of effector function-related molecules such as IFN-γ,Granzyme B,Perforin and CD107a without statistical significance.Furthermore,the activation receptors CD16a and CD69 were significantly increased,NKP46 was significantly decreased,the inhibitory receptor NKG2A was significantly increased,while CD96 was significantly decreased on hESC-NK cells of DH groups(P<0.05).Conclusively,enhancing the signals for definitive hematopoiesis during hESC differentiation into hematopoietic stem/progenitor cells significantly improves the yield of NK cells and the expression of CD16a without affecting their in vitro effector functions.Our study provides a new approach to improving the efficiency of hESC-NK cell or iPSC-NK cell generation.

BACKGROUNDTo evaluate and compare the effects and toxicity of the domestic product of recombinant mutant human tumor necrosis factor (rmhTNF) combined with chemotherapy and chemotherapy alone in the treatment of patients with non-small cell lung cancer (NSCLC).

METHODSTwo hundred patients with NSCLC in multicenter were randomly devided into trial group (150 cases) and control group (50 cases). Chemotherapy with CAP regimen was given to the patients. Meanwhile, rmhTNF injection of 4×10⁶U/m² was also given from the 1st to 7th days, the 11th to 17th days on the chemotherapy cycle in the trial group. The control patients received chemotherapy alone. Twenty-one days were as a cycle, 2 cycles were given to each patient. The chemotherapeutic effects and toxicity were observed and compared between the two groups after the therapy.

RESULTSof the 200 patients, 5 cases in the trial group and 3 cases in the control group were out of the trial because of economy. The other 192 cases (145 cases in the trial group and 47 cases in the control group) could be analyzed and evaluated the clinical effects and toxicity. The response rate of chemotherapy was 46.90% (68/145) in the trial group and 17.02% (8/47) in the control group respectively ( P =0.001). The KPS scores was 86.02±9.74 in the trial group, and 80.14±9.10 in the control group ( P =0.025). No significant difference of degree III+IV toxicity was observed between the two groups ( P > 0.05). The side effects related to rmhTNF included slight fever, cold-like symptoms, pain and red and swelling in the injection site. All of them were mild and didn't need any treatment and disappeared after the therapy. There were no severe abnormality of liver and kidney function and ECG in both groups.

CONCLUSIONSThe results demonstrate that the effects of domestic rmhTNF combined with chemotherapy are remarkably higher than that of chemotherapy alone in the treatment of NSCLC. rmhTNF can increase the sensitivity to chemotherapy and improve the quality of life of the patients with slight toxicity. Hence rmhTNF is worth expanding clinical use.

Humans ; Consensus ; Liver Neoplasms/therapy* ; China