The activation of MAPKs signal transduction parthways, is a typical feature of chronic synovitis in rheumatoid arthritis. The phosphorylation of synoviocytes cytoplasm proteins induced transcription factor and nucleus proteins phosphorylation such as c-fos, c-jun, AP-1 and NF-?B via MAPKs signal transduction, which promotes synoviocytes proliferation and activation. These findings may be beneficial for the elucidation of the pathogenesis and the development of new drugs for rheumatoid arthritis.

Lymphoma is a malignancy of mature lymphocytes. Signalling through the B cell receptor ( BCR ) is central to the development and maintenance of B cells. In light of the numer-ous proliferative and survival pathways activated downstream of the BCR, it comes as no surprise that malignant B cells would co-opt this receptor to promote their own growth and survival. Compounds that inhibit various components of this pathway, in-cluding spleen tyrosine kinase(Syk), Bruton’s tyrosine kinase (Btk), and phosphoinositol-3 kinase(PI3K), have been devel-oped. In this paper,the B-cell receptor signaling and its targeted inhibitors of lymphoid malignancies are reviewed.

Sarcomas collectively represent over 100 different subtypes of bone and soft tissue tumors.They are not sensitive to chemotherapy,which requires the development of tissue-specific or pathway-specific therapies.As our understanding of the molecular mechanisms driving sarcomas is rapidly advancing,the number of targeted therapies is also increasing.Recently identified novel druggable targets including the MDM2 amplifications in welldifferentiated and dedifferentiated liposarcomas,the fusion NAB2:STAT6 of solitary fibrous tumor,the SDH mutations in gastrointestinal stro mal tumors,the suppression of Mcl1 in synovial sarcomas,CDK4 in alveolar rhabdomyosarcoma.They will play an important role in the treatment of sarcoma.Here,the author do an overview of these factors.

Objective To explore the effects of Kangshuaiyizhi capsule on ChAT/AchE and NE, DA and 5-HT levels in the brain tissue of aging model rats, and explore its effect of protecting cerebral function. Methods Totally 72 rats were randomly divided into normal group and model group. The subacutely aging model rats were made by injecting D-gal (0.125 g/kg) into abdominal cavity continually, then aging rats were divided by random number table into model group, Naofukang group and Kangshuaiyizhi high-, low-dose group. After intervented with correspongding drugs for 60 days, activity of ChAT and AchE, cerebral cortex NE, DA, and 5-HT levels were detected. Results Activity of AchE was much higher (P<0.05), but level of ChAT, NE, DA and 5-HT in model group were significantly downregulated compared with normal group (P<0.05). After treated with Kangshuaiyizhi capsule, activity of AchE was downregulated, ChAT, NE, DA and 5-HT levels were significantly upregulated (P <0.01, P <0.05). Conclusion Kangshuaiyizhi capsule can regulate cholinergic and monoamine neurotransmitter levels in the brain tissue of aging model rats, and play a very important role in protecting cerebral function.

Objective To observe effects of Kangshuai Yizhi Capsule on ATP in brain tissue and IL-6, TNF-α in serum of aging model rats, and explore the protective effects of the capsule on brain tissue.Methods Totally 72 rats were randomly divided into a normal group and a model group. The subacutely aging model rats were made by injectingD-gal, then aging rats were numbered and grouped by random number table into the model group, Kangshuai Yizhi high-dose group, Kangshuai Yizhi Capsule low-dose group and Naofukang group. All dose groups were received gavage by giving corresponding doses, while normal group and model group were given the same amount of saline everyday. After treated for 60 days, the activity of Na+-K+-ATP and Ca2+-Mg2+-ATP in brain tissue, and IL-6, TNF-α in serum were detected.Results Compared with normal group, Na+-K+-ATP and Ca2+-Mg2+-ATP were less active (P<0.05), but levels of IL-6 and TNF-α in model group were significantly higher, with statistical significance (P<0.05). Compared with model group, after treated with Kangshuai Yizhi Capsule, Na+-K+-ATP and Ca2+-Mg2+-ATP were more active, and IL-6 and TNF-α levels were down-regulated significantly in dose groups, with statistical significance (P<0.05). Meanwhile, Kangshuai Yizhi Capsule high-dose group showed the most obvious effect among dose groups.ConclusionKangshuai Yizhi Capsule has effects of enhancing activity of ATP in brain tissue and reducing level of proinflammatory factors.

ObjectiveTo detect the expressions of Nuclear factor-erythroid 2 p45-related factor 2 (NRF2) and multidrug resistance-associated protein 2 (MRP2), and investigate their significance in primary gallbladder carcinoma. MethodsImmunohistochemistry SP assay and image analysis were used to detect the expressions of NRF2 and MRP2 protein in 59 patients with primary gallbladder carcinoma. ResultsA highly positive expression rates of NRF2 and MRP2 were found (76.3% and 74. 6%, respectively) in primary gallbladder carcinoma. The expressions of NRF2 and MRP2 had a significantly correlation with metastases, Nevin staging, and differentiation (P＜0.05), but there was no statistical association with sex and age. The expression of NRF2 had a positive correlation with MRP2 (r=0. 589,P＜0.05). Conclusion Both NRF2 and MRP2 were overexpressed in primary gallbladder carcinoma and they may play a role in the development of primary gallbladder carcinoma.

Objective To investigate the biological function of M122 in pathogenesis of MCMV in developmental brain disorders and brain damage, screening for mouse brain cDNA library interacting with M122 was performed by a yeast two-hybrid system. Methods The reconstructed bait plasmid pGBKT7-M122 was transformed into yeast cells AH109 and screened on the nutrient deficiency medium SD/-Trp. After express of the bait protein in AH109 yeast strains was detected by Western blot analysis, yeast-two hybrid screening was performed by mating AH109 with Y187 containing mouse brain cDNA library plasmid. The diploid yeast cells were plated on the nutrient deficiency medium SD/-Trp/-Leu/-His/-Ade. The second screening was performed with SD/-Trp/-Leu/-His/-Ade containing X-α-gal. The plasmids in positive colonies were extracted and transformed into E. coli JM109 cells. After plasmid DNA in JM109 cells were extracted form positive colonies and sequenced, the results were analyzed by bioinformatic methods. The interactions between M122 protein and the protein obtained from positive colonies were further confirmed by repeating yeast-two hybrid. Then, autoactivations of the proteins obtained from positive colonies were detected.Results The reconstructed bait plasmid was transformed into yeast cells AH109 successfully. The bait protein expressed in the yeast cells AH109 stably. 24 proteins interacting with MCMV M122 were screened, including syntaxin 8 ( Stx8 ), phosphoglucomutase 2 ( Pgm2 ), potassium voltage-gated channel, shaker-related subfamily, beta member 1 ( Kcnab1 ), collagen, type ⅪⅩ, alpha 1 ( Col19a1 ), archain 1 ( Arcn1 ), cytidylate kinase( Cmpk), DnaJ(Hsp40) homolog, subfamily A, member 1 (Dnaja1), ATPase, Na+/K + transporting, beta 3 polypeptide( Atp1b3 ), SH3-domain GRB2-like ( endophilin ) interacting protein 1 ( Sgip1 ),ankyrin repeat domain 17 (Ankrd17), Smg-7 homolog, nonsense mediated mRNA decay factor(Smg7),sperm associated antigen 9 ( Spag9 ), FK506 binding protein 1a ( Fkbp1a), MYST histone acetyltransferase monocytic leukemia 4 ( Myst4), hyaluronan and proteoglycan link protein 1 ( Hapln1), autophagy-related 3 (Atg3), splicing factor, arginine/serine-rich 5 ( Sfrs5 ), zinc finger, C3HC-type containing 1 ( Zc3hc1 ),thioredoxin-related transmembrane protein 1 ( Txndc1 ), adaptor protein complex AP-1, gamma 1 subunit (Ap1g1), Cullin 1 ( Cul1 ), and so on. Three of them were formerly unknown proteins. M122 protein could interact with the proteins obtained from positive colonies in the yeast cells AH109. Ap1g1 and Cul1 were proved to have autoactivation. Conclusion A class of proteins in brain interacting with M122 has been obtained. It is presumed that these proteins are correlated with neuropathogenesis of the brain disorders caused by CMV, but the candidates still need further confirmation for the interaction.

Objective To establish animal model of arterial vulnerable plaques for molecular imaging study.Methods Fifteen New Zealand white rabbits were randomly divided into high lipid diet+balloon-injury group (A),high lipid diet group (B)and regular diet group (C).Ultrasound (US)and magnetic resonance (MR)imaging were used to dynamically observe the formation of plaque in abdominal aorta. Results were compared with blood lipid level and pathological indicators.Results At 4 weeks,several plaques could be seen in group A.The plaque number increased rapidly and reached to 22 at 12 weeks,which was in parallel with the change of blood lipid. Only a few plaques were observed in group B,while no vulnerable plaque was revealed in group C.All the plaques were judged to be soft plaques on US and MR images,which was consistent with the macrophages gathering and smooth muscle cell proliferating in plaques.Conclusion High lipid diet+balloon-injury is an ideal method to build animal model for molecular imaging of atherosclerotic plaque.

Aim To observe the variation of T-cell subsets in spleen in different courses of disease and tis-sue histopathological changes in rats with adjuvant ar-thritis (AA).Methods The model of rat AA was in-duced by complete Freund’s adjuvant into the right hind metatarsal footpad of 20 male Lewis rats.Arthritis was evaluated by total score,arthritis index and paw swelling number. The percentage of total (CD3 +CD4 +), memory (CD4 + CD44 +), no-sensitizated (CD4 + CD62L +) and Th1 7 (CD4 + IL-1 7 +) on CD4 +T cells in spleen were detected by flow cytometry on days 1 4 and 22 after immuniozation.The his-topathological evaluation of heart,liver,spleen,lung, kidney,ankle joints and mesenteric lymph nodes were examined by hematoxylin and eosin (HE)stain.Re-sults The onset of secondary arthritis appeared on a-bout day 1 0 after immunization,with a peak onset on day 1 9.Systematic arthritis symptoms included front and hind paw swelling and redness (swelling was more apparent in the front rather than hind paws),nodule formation and redness on the ears,connective tissue swelling and redness of the nose and evident nodules and redness on the tail.Total score,arthritis index and the paw swelling numbers were enhanced in AA rats. Pathohistology of ankles joints showed hyperplasia, pannus formation,and inflammatory cells infiltration in AA rats.And pathohistology of heart,liver,spleen, kidney and mesenteric lymph nodes showed inflamma-tory changes.Compared with normal group,there was no change in the percentage of total,memory and no-sensitizated CD4 +T cell in the early stage inflammation but they were significantly enhanced in the peak of in-flammation.Th1 7 cell subsets were significantly en-hanced in both of the early and peak of inflammation. Conclusion These findings suggest that abnormal T cell responses and tissue histopathological changes are important features of AA rats.

OBJECTIVE:To investigate the prognosis of coronary heart disease complicated with heart failure patients abandon-ing percutaneous coronary intervention (PCI) and receiving drug comprehensive therapy. METHODS:From Dec. 2010 to Jul. 2012,217 patients with coronary heart disease complicated with heart failure in our hospital were divided into operation group (105 cases) and non-operation group (112 cases). Based on routine treatment,operation group was given aspirin combined with clopidogrel before and after PCI,and non-operation group was given aspirin combined with clopidogrel all the time. The patients were followed up regularly during discharging from hospital to May 2015 by outpatient,telephone and coronary angiography re-checking,lasting for 24-38 months. Death cases,readmission and revascularization again caused by main adverse cardio-cerebrovas-cular events were recorded during follow-up period. RESULTS:7 cases and 8 cases in operation group and non-operation group did not accept follow-up;median follow-up time was 33 months and 32 months,respectively. Case number of myocardial infarction, heart failure and death in non-operation group was more than operation group,with statistical significance (P<0.05). 94 patients survived in operation group in 3 years,with survival rate of 95.9%;66 in non-operation group,with survival rate of 63.5%;with statistical significance(P<0.05). The survival time of non-operation group was shorter than that of operation group,with statistical significance(P<0.05). CONCLUSIONS:Although we still cannot get the conclusion that PCI is a better treatment or drug therapy is better. But the survival rate of patients are not optimistic 3 years after abandoning PCI coronary heart disease patients with severe myocardial ischemia should choose PCI firstly.