The genesis of malignant tumor is proved to be mainly caused by regulatory disturbance of cell cycle,in which p27 protein and cyclin D1 protein are major regulators.Cyclin D1 and p27 are positive andnegative regulator respeetively.Recently,redueed expression of p27 protein and overexpression of cyclinD1 pro-tein are found in various eaacers.It has been demonstrated that p27and cyelinD1 are closely associated with the genesis and development of many cancers.Cell cycle and its regulatory has become the focus in tumor research.

G-protein-coupled receptors (GPCRs) are major targets for drug discovery. The regulator of G-protein signaling (RGS) proteins is a recently identified protein family,which strongly modulates the activity of G proteins. RGS proteins accelerate the deactivation of G proteins to reduce GPCR signaling; however, some also have an effector function and transmit signals. Combining GPCR agonists with RGS inhibitors should potentiate responses and markedly increase the regional specificity of agonist. In the central nervous system, RGS proteins have unique tissue distributions and are strongly regulated by signal transduction events. Thus the diversity of RGS makes them attractive targets for pharmacotherapy of neurological disorders.

Statins not only can help lower cholesterol,but also has certain effect for the treatment of malignant tumor.Its possible antitumor mechanisms include inducing apoptosis and differentiation,inhibiting tumor cell proliferation,reducing the invasion and metastasis of tumor cells,combined sensitization and chemical prevention effect.

The pathogenesis of multiple sclerosis ( MS) involves alterations to multiple pathways and processes, which represent a significant challenge for developing more-effective therapies.In MS, abnormalities have been identified in several cytokine-signaling pathways, as well as those of other immune receptors.Among the downstream molecules implicated are Jak/Stat, NF-κb, ERK1/2, p38 or Jun/Fos, current MS drugs target some of these pathways.This article will with the aid of the latest research results of systems biology approaches that study pathway dysregulation in the process of MS development, targeting these relevant MS-signaling pathways, offers the opportunity to accelerate the development of novel individual or combination therapies for the future of new drug research.

Objective To investigate the risk factors for poor response to treatment in juvenile-onset systemic lupus erythematosus (SLE).Methods The clinical manifestations,treatment and follow up data of the initial onset SLE patients in our hospital were collected retrospectively.According to the response to treatment after 6 months,patients were divided in two groups.One was treatment effective group,and the other was poor response group.The data of the two groups were analyzed by SPSS 16.0 Counted data were analyzed by Chi-square test.Measurement data were analyzed by t-test.The areas under ROC curve of the measurement data which had statistical significance were calculated and further Logistic regression analysis were made.Results In all of the 82 patients with first onset SLE,72 patients were in the treatment effective group and 10 were in the poor response group.Boy gender (5/10 & 12/72,x2=5.937,P=0.015),edema (10/10 & 25/72,x2=15.294,P＜0.O1) and serositis (8/10 & 25/72,x2=7.485,P=0.006),higher positive rate of Coombs' test (7/8 & 14/29,x2=3.931,P=0.047) and histological class Ⅳ or Ⅳ+Ⅴ of lupus nephritis (8/9 & 6/30,x2=14.278,P＜0.01) were more common in the poor response group.The level of hemoglobin (P=0.013),serum albumin (P=0.001) and globulin (P=0.004),creatinine clearance (P＜0.01),serum calcium (P=0.040) and immunoglobulin (P=0.006) of the patients in the poor efficacy group were lower than those of patients in the treatment effective group.The level of serum potassium (P=0.011),serum phosphorus (P=0.035),24 hours proteinuria (P=0.001) and SLEDAI (P=0.002) of the patients in the poor response were higher than those patients in the treatment effective group.The creatinine clearance was lower than 75.91 ml·min-1· 1.73 m-2,24 hours proteinuria was higher than 1 771.5 mg and SLEDAI was higher than 11.5 could be the diagnostic cutoff value to predict the poor response to treatment in juvenile-onset SLE patients.The results of Logistic regression analysis showed creatinine clearance lower than 75.91 ml ·min-1· 1.73 m-2 was the risk factor that could influence the outcome of SLE patients (P=0.043).The OR was 23.9 and 95％CI was from 1.10 to 516.8.Conclusion In juvenile-onset SLE patients,boys have poor response to treatment.The creatinine clearance lower than 75.91 ml·min 1· 1.73 m-2,24 hours proteinuria higher than 1 771.5 mg and SLEDAI higher than 11.5 can predict the poor response to treatment in juvenile-onset SLE patients.In addition,the SLE patients with autoimmune hemolytic anemia may have poor response to treatment.

Microglia are the inherent macrophages and immune surveillance cells in the central nervous system (CNS) and compose the first guard of immune defense in CNS .The activation of microglia is one of the pathological features of many CNS diseases and acts as an important role during the multiple sclerosis (MS) process.MS is a CNS disease characterized by neuroinflammatory infiltration , demyelination and axonal damage.Accumulation of activated microglia at the injury site has been observed in brains of MS patients and experimental animals with complicated mechanisms.Microglia have both detrimental and beneficial roles .For instance, microglia have been shown to recruit and reactivate T cells in the CNS and release many detrimental molecules such as proteases , inflammatory cytokines, and free radicals.Conversely, they have also been observed to aid in axonal regeneration and remyelination as well as assist in the clearance of inhibitory myelin debris .In addition, microglia have been shown to release a variety of neurotrophic factors . Cuprizone [oxalic acid bis (cyclohexylidene hydrazide )] is a well-known copper-chelating agent.Cuprizone ingestion in mice induces a highly reproducible demyelination of distinct brain regions .Discussion on the detrimental and beneficial aspects of microglia in cuprizone animal models will serve to better understand the development of MS and find out new therapeutic targets.This review will further our understanding of the dichotomous roles of microglia in cuprizone -induced demyelination in animal models of multiple sclerosis .

Multiple sclerosis ( MS) is an autoimmune disease of the central nervous system ( CNS) characterized by demyelination and inflammation lesions.MS predominantly affects young adults with a high incidence of disability. However, the exact pathogenesis of MS is still not clear.Studies found that microglia polarization tending to pro-inflammatory M1-like state during the onset of MS, causing the M1/M2 ratio imbalance, forming pro-inflammatory microenvironment state, and which further leading to nervous tissue damage ultimately.Microglia polarization may be considered as the initiator of pathologic alterations by releasing pro-inflammatory cytokines and secondarily trigger the initial microglia response.Given the pivotal role of imbalanced microglia polarization in MS initiation, a critical review of microglia polarization is presented here, in order to elucidate the pathogenesis of MS and highlight the noteworthy candidate therapeutic targets for clinic treatment.

Objective To investigate the efficacy and safety of Lipo-prostaglandin E1 (LipoPGE1) in the treatment of non-ST segment elevation acute myocardial infarction (NSTEAMI).Methods A total of 86 patients with NSTEAMI were randomly and equally divided into LipoPGE1 group (n= 43) which received intravenous LipoPGE1 combined with low-molecular-weight heparin,aspirin, clopidogrel and other basic therapy, and the control group (n=43) which received placebo combined with the same therapy. The basic clinical settings, curative effect, main adverse cardiovascular events (MACEs) within 30 days including sudden death, new-onset myocardial infarction and target vessel revascularization, bleeding complications and drug adverse effects were observed. Results There were no significant differences in basic clinical characteristics between the two groups. Compared with control group, the patients in LipoPGE1 group showed. significant improvements of ECG (93.0% vs. 74.4%), angina (95.3% vs. 81.4%, both P＜0. 05), the incidences of left heart failure (2.3% vs. 14.0%) and MACEs within 30 days (4.7% vs.18.6%)(both P＜0.05). There were no serious drug adverse effects. Conclusions The LipoPGE1 combined with heparin, aspirin and clopidogrel is effective and safe in the treatment of NSTEAMI,which could improve the clinical symptoms, distal myocardium perfusion and cardiac function,decrease the incidence of MACEs.

OBJECTIVE: Panel reactive antibody (PRA) can induce acute rejection following kidney transplantation, however, it is poorly understood which PRA is more associated with rejection. Therefore, the aim of this study is to analyze the correlation between PRA and rejection by observing the change of PRA Ⅰ and PRA Ⅱ prior to and after the kidney transplantation. METHODS: Levels of PRA Ⅰ and PRA Ⅱ were observed in 100 patients received kidney transplantation at the Department of Urology, Beijing Chaoyang Hospital Affiliated to the Capital Medical University. During these 100 patients, 18 patients had PRA changes after operation. The relationship between PRA changes after kidney transplantation and acute rejection were analyzed. RESULTS: Totally 18 patients were included in the final analysis. Nine of them occurred acute rejection with obviously increased PRA Ⅱ (P=0.040), however, the PRA Ⅰ had no significant changes (P=0.707). The changes of PRA Ⅰ and PRA Ⅱ had no significance in the remaining 9 patients prior to and after kidney transplantation. The overall level of PRA increased in 7 patients, in 5 patients with increased PRA Ⅱ, 4 patients suffered acute rejection, 1 of which was renal allogreft failure; 2 cases with PRA Ⅰ increasing did not occur acute rejection. The overall level of PRA declined in 11 patients, including 5 patients with PRA Ⅱ decreased, 1 patient occurred acute rejection; 4 patients in 6 patients with PRA Ⅰ declined suffered acute rejection. CONCLUSIONS: The increased PRA Ⅱ after transplantation easily result in acute rejection, which has definite correlation to acute rejection, however, the PRA Ⅰ changes has no impact on acute rejection.

Objective To discuss the feasibility of establishing the model of combining myocardial ischemic coronary disease with syndrome of kidney deficiency and blood stasis by surgical method.Methods Non-disease of kidney deficiency and blood stasis syndrome model was built by taking the methods of fright, being placed in a cold environment and injection of hydrocortisone. The model of combining the myocardial ischemic coronary disease with the syndrome of kidney deficiency and blood stasis was established through ligating the left anterior descending branch of artery and injecting hydrocortisone. The rats were divided into kidney deficiency and blood stasis group, combination of disease and syndrome group, and normal group, 5 rats in each group. The temperature, weight, heart rate, breathing rate and whole blood viscosity, casson viscosity of the rats in the two groups before and after modeling were observed. According to TCM clinical diagnosis criteria of kidney deficiency and blood stasis syndrome, TCM syndrome characteristics of the two groups were compared.ResultsCompared with normal groups and before modeling, rat temperature dropped and breathing rate increased in kidney deficiency and blood stasis group, combination of disease and syndrome group (P<0.05). Compared with normal group, rat weight decreased or grew slowly, and whole blood viscosity and casson viscosity increased (P<0.05, P<0.01). There were statistical significant differences in whole blood viscosity and electrocardiogram between the two groups (P<0.05).Conclusion There is no obvious difference between TCM syndrome characteristics of the two groups. They all meet the TCM clinical diagnosis criteria of kidney deficiency and blood stasis syndrome.