Objective: To study the effect of ipilimumab on T lymphocytes and Bcl-2 mRNA expression in lung cancer-bearing mice by inhibiting TGF-β1/ERK signaling pathway. Methods: Forty-five C57 mices inoculated with Lewis lung cancer cells were randomly divided into control group, low dose ipilimumab group and high dose ipilimumab group with 15 mice in each. The low and high dose groups were given 3 mg/kg and 5 mg/kg ipilimumab respectively, while the control group was given 0.9% sodium chloride solution with the same volume. The effects of ipilimumab on TGF-β1/ERK signaling pathway, Bcl-2 mRNA expression, immune function improvement and tumor inhibition in three groups were detected by WB and qPCR. Results: After administration of ipilimumab, the tumor weight and volume of mice in low-dose and high-dose groups were significantly lower than that of the control group, and the tumor inhibition rate increased in a dose-dependent manner (P<0.05). The thymus index and spleen index of mice were significantly higher than that of control group, which also increased in a dose-dependent manner (P<0.05). The levels of CD3+, CD4+, CD4+/CD8+ cells in the high and low dose groups were significantly higher than those in the control group, with significantly higher levels in high dose group compared with the low dose group (P<0.05). The levels of serum inflammatory factors were significantly lower than those in control group, and the levels of serum TNF-α, IL-6 and IL-3 in the high dose group were significantly lower than those in the low dose group (P<0.05). The expressions of TGF-β1, ERK1/2, p-ERK1/2 and MEK in tumor tissues of both high and low dose groups significantly decreased, with more lower levels in high dose group than in low dose groups (all P<0.05), and the positive rate of TGF-β1 expression in high dose group was the lowest. The mRNAexpression of Bcl-2 in tumor tissues of high and low dose groups decreased significantly after drug administration, with a significantly lower level in high does group than that in low dose group (P<0.05). Conclusion: Ipilimumab can effectively inhibit TGF-β1/ERK signaling pathway, improve immune function and down-regulate the expression of Bcl-2, thus inhibit the growth of Lewis lung cancer cells and play an antitumor role in mice.

Objective To study the relation of leptin,TNF-? in serum of patients with metabolic syndrome and its components.Methods Test leptin and TNF-? level of residents over 20 years old in two communities in Harbin City,grouping case-control study base on the constitutive ratio of actual age.Results Leptin was associated with obesity,and the higher leptin levels,the higher risk of suffering from metabolic syndrome.The relationship between leptin levels and metabolic syndrome was affected by age and gender.The lower level of TNF-?,the higher risk of metabolic syndrome.The patients with lower level of TNF-? were 1.859 times more likely to suffer from disease compared with people with higher level.Conclusion The effects of high level of leptin are significant on metabolic syndrome,especially for old males,and are associated with obesity component.TNF-? is related to plasma glucose and blood presure,and is good for metabolic syndrome,but its biological mechenism should be researched continuously.

ObjectiveTo explore the association of smoking to the Aspirin and Clopidogrel antiplatelet in patients with stable angina after percutaneous coronary intervention (PCI). Methods241 smoking patients and 252 non-smoking patients underwent PCI for stable coronary artery disease, all patients had taken aspirin 100 mg/d for 7 d or more. The arachidonic acid (AA)- and adenosine diphosphate (ADP)-induced platelet aggregation were tested as they got in hospital. Then, they accepted Clopidogrel 300 mg as loading dose, continued with 75 mg/d for 3 d. The ADP-induced platelet aggregation were re-tested. ResultsThe incidence of aspirin resistance (AR) and aspirin semiresponder (ASR) was 19.1% in all the cases, and was 25.5% in smoking group, 14.3% in non-smoking group (P=0.027). Age (OR=3.79，95%CI: 1.77～8.12) and smoking (OR=1.98，95%CI: 1.18～4.43) were the independent risk factors of AR and ASR. The incidence of Clopidogrel resistance was 19.5% in all the cases, and was 13.2% in smoking group, 24.3% in non-smoking group (P=0.03). Smoking (OR=0.22，95%CI: 0.09～0.54) may reduce the risk of Clopidogrel resistance. ConclusionSmoking increased the risk of AR and ASR, but reduced the risk of Clopidogrel resistance.

Objective To observe the effect of Zhuyun Capsule(Pregnant-promoting Capsule)on serum sex hormone and expres- sion of ovarian cytokine of polycystic ovary syndrome(PCOS)rats.Methods Progestogen plus human chorionic gonadotrophin (HCG)was adopted to make PCOS rat models.Totally 40 SD rats were randomized into control group,PCOS model group,Zhuyun Capsule group,and clomiphene citrate group with 10 in each.Radioimmune assay(RIA)was used to measure the sex hormone and immunohistochemical test was done to measure the expression of tumor necrosis factor-?(TNF-?)of ovarian tissue,insulin-like growth factors-1(IGF-1),and leukemia inhibitory factor(LIF)to analyze the relations among these factors.Results Zhuyun Capsule could reduce greatly serum testosterone(T)and luteinizing hormone(LH),decrease expression of TNF-?and IGF-1,but increase expres- sion of LIF.Conclusion Zhuyun Capsule could regulate endocrine function and expression of ovarian cytokine to improve gonad func- tions of PCOS rats and to promote the maturation of follicle and ovulation.

Drugs, Chinese Herbal ; Humans ; Integrative Medicine ; Medicine, Chinese Traditional

Objective To construct a mutant strain of Aspergillus fumigatus with the mutant pbs2 gene, and to investigate the effect of the mutant gene on the morphology of A. fumigatus, the variation of os-motic pressure and the sensitivity of oxidative stress. Methods S. cerevisiae pbs2 gene homologs was identi-fied in A. fumigatus genome database. A PCR fragment, composed of the 5' flanking sequence(approximate-ly 1 kb) ofpbs20RF and its 3' flanking sequence (approximately 1 kb), was subcloned into a vector pDHt/SK with Xho Ⅰ/Xba Ⅰ enzyme to produce a recombinant plasmid PA. The selected marker pryG amplified from pLAX223 was cloned into PA with BamH Ⅰ/Pst Ⅰ enzyme to produce plasmid PB. PB was transformed into Agrobacterium tumefac/ens and named plasmid At pbs2. Then At pbs2 was transformed into A. fumigatus strain AF293.1 (pyrG) via ATMT to produce the transformants △pbs2. To observe the growth rate and the phenotype on the MM containing different oxidative stress and osmotic pressure between the △pbs2 and the wild type. Results There were no visible difference between △pbs2 and AF293 on the radial growth rate and morphology. △pbs2 mutant was not only more sensitive to osmotic pressure produced by sodium chloride and glycerol but also sensitive to oxidative stress produced by hydrogen peroxide than the wild type. Conclu-sion The pbs2 gene plays a role in osmotic pressure and oxidative stress signal tmnsductions in A. fumiga-tus but only involved in oxidative stress induced by hydrogen peroxide specifically. However, pbs2 gene has a minor effect on growth and morphology in A. fumigatus.

to common antifungal drugs.

Adult ; Anti-Inflammatory Agents ; therapeutic use ; Churg-Strauss Syndrome ; drug therapy ; pathology ; Follow-Up Studies ; Humans ; Male ; Methylprednisolone ; therapeutic use

Objective:To analyze the relationship of lipoprotein associated phospholipase A 2 (Lp-PLA2) and severity of coronary atherosclerosis, and evaluate the effects of rosuvastatin at different doses on the concentration of plasma Lp -PLA2.Methods: Totally 152 cases of patients with suspected coronary heart disease were treated with coronary angiography .According to the results of angiogra-phy, the patients were divided into the coronary heart disease group ( n=117 ) and the normal control group ( without coronary heart disease,n=35).Gensini integral scale was performed and referring to the number of diseased coronary arteries , the degree of coronary atherosclerosis was evaluated .The concentration of serum Lp-PLA2 was detected and the relationship of Lp-PLA2 and the severity of coronary plaque was evaluated .Meanwhile , the patients with coronary heart disease were divided into 2 groups and orally treated with rosuvastatin respectively at the routine dose (10 mg· d-1 ) and the loading dose (20 mg· d-1 ).The changes of the plasma concentra-tion of Lp-PLA2 before the treatment, in the 2nd, 4th,8th and 12th week after the medication were measured and the effect of atorvastatin at different doses on the plasma concentration of Lp-PLA2 was summarized .Results: The plasma Lp-PLA level in the control group was (22.22 ±1.75) μmol· ml-1, while that in the coronary heart disease group was (29.03 ±3.99) μmol· ml-1(P<0.05).The differences in Lp-PLA2 levels between the groups with different Gensini scores of coronary heart disease were statistically significant ( P<0.05).The higher scores were, the higher Lp-PLA2 levels were.The results of multivariate analysis showed that the severity of cor-onary atherosclerosis was significant and positive correlated with Lp-PLA2 level (OR=1.613,P<0.05).In the 2nd, 4th, 8th and 12th week after the medication , Lp-PLA2 levels in the loading dose group were significantly lower than those in the routine dose group ( P<0.05).In the 2nd, 4th, 8th and 12th week after the medication, the degree scores of coronary artery stenosis in the loading dose group were reduced.The decreasing range was significantly greater than that in the routine dose group (P<0.05).The incidence of adverse cardiovascular events in the routine dose group (27.12%) was significantly higher than that in the loading dose group (6.90%) ( P<0.05).The incidence of adverse drug reactions in the routine dose group was 11.86%, while that in the loading dose group was 18.97%(P>0.05).Conclusion:Lp-PLA2 is correlated with the severity of coronary plaque .High dose of rosuvastatin can reduce plasma Lp-PLA2 concentration in the patients .

Objective:To investigate the efficiency of Agrobacterium tumefaciensmediated transfor-mation of Aspergillus fumigatus by using pyrG as a recessive selectable marker.Methods: FAP1 and SHO1 genes target sequences,composed of a selectable marker pyrG and the flanking sequences of the FAP1 and the SHO1 genes,were cloned into a binary plasmid pDHt/sk,respectively.The produced plasmids were transformed into A.tumefaciens.The A.tumefaciens and uracil auxotroph A.fumigatus were cocultured in induction medium without uricil and uridine at 24 ℃ for 48 h.To inhibit growth of A.tumefaciens and to select transformants,the cultures were transferred to 37 ℃ and incubated for another 48 h.Results: In this study,A.tumefaciens-medidated transformation of A.fumigatus produced high homologous recombination rates,which was 44%(7 of 16) for FAP1 and 35%(7 of 20) for SHO1.Conclusion: Our study showed that A.tumefaciens-medidated transformation by using pyrG as a recessive selectable marker is an efficient tool for target gene deletion of A.fumigatus.