AIM: To study the role and the mechani sm of heme oxygenas/endogenous carbon monoxide on nitric oxide synthase/nitric oxide system in rats with pulmo nary hypertension induced by hypoxic hypercapnia. METHODS: Spr ague-Dawley rats w ere randomly divided into three groups: control group (A group),hypoxic hypercap n ic group (B group), hypoxic hypercapnia+hemin group (C group). Blood CO concentr at ion (COHb%),NO concentration,HO-1 activity, iNOS, cNOS in blood serum and lung h omogenate were measured, respectively. RESULTS: ① mPAP and RV /(LV+S) of B g roup were significantly higher than those of A and C group( P

To explore the expression and clinical significance of molecular chaperone heat shock protein 90 (HSP90) in peripheral blood mononuclear cells (PBMC) and plasma level of interleukin-6 (IL-6) in patients with systemic lupus erythematosus (SLE), HSP90 was detected in PBMC by Western blot assay and the plasma level of IL-6 was measured by ELISA in 38 SLE patients and 20 normal controls. The correlation analysis was performed between the SLE disease activity index (SLE-DAI) and the expression of HSP90 and IL-6. The results showed that there was increased expression of HSP90 in the SLE patients. The active SLE group exhibited higher HSP90 levels (0.82+/-0.10) than the inactive SLE group (0.54+/-0.09) (P<0.01). The expression of HSP90 in normal control group (0.37+/-0.11) showed significant statistical difference as compared to both the inactive and active SLE groups (P<0.01, P<0.01, respectively). The plasma level of IL-6 exhibited a significant increase in both the inactive and active SLE groups (28.99+/-1.74 pg/mL, 44.58+/-9.15 pg/mL, respectively) compared with normal control group (P<0.01, P<0.01, respectively). The expression of HSP90 and IL-6 in SLE patients showed significant positive correlation with SLEDAI scoring (r=0.80, P<0.01: r= 0.74, P<0.01, respectively). In addition, there was a positive correlation between the level of IL-6 and HSP90 in SLE patients (r=0.86, P<0.01). The increased expression of molecular chaperone HSP90 and IL-6 may play an important role in the pathogenesis of SLE by regulating autoimmunity.

Currently,a physiologically based pharmacokinetic(PBPK)model plays a key role in pharmaceutical research,which has been widely used at each stage of drug discovery and develop?ment. In the process of drug discovery,the selection of drug candidates is finished using the PBPK model to predict the pharmacokinetic properties of the drugs. In the process of preclinical development , through a combination of in vitro and physiological data amplification coefficient,the PBPK model can be used to predict not only the overall pharmacokinetic behavior of drug candidates in humans and animals and in vitro metabolism experiments,but also drug-drug interactions(DDI). In the course of clinical development,the PBPK model can help predict the difference between reference populations (age,different disease state,and polymorphism),especially the dosage and sampling time of the children. At present,the input parameters of PBPK model are mostly the mean values of the population,making it difficult to serve individuals. It is hoped that the input parameters of the model can reflect more of the individual characters according to the individual requirement,and that the time parameters of the input accord more with the actual physiological condition. In this article ,we briefly introduced the characteristics of common PBPK software,and reviewd the principle and feature of the PBPK model,as well as its application to drug discovery,preclinical development and clinical development,DDI,and individualized medication.

Objective To investigate the effect of internal fixation with proximal femoral nail antirotation (PFNA) and bone cement on peritrochanteric tumors due to metastatic carcinoma.Methods Clinical data of 19 patients with peritrochanteric tumors due to metastatic carcinoma during June 2007 and July 2013 treated with PFNA and bone cement were retrospectively analyzed.Results Visual analogue scale(VAS) was (8.37 ± 1.12) scores before surgery,and (2.58 ± 1.26) scores after 3 d surgery.There was significant difference (t =22.45,P ＜ 0.05).Conclusion For patients with peritrochanteric tumors due to metastatic carcinoma,internal fixation with PFNA and bone cement is an effective way to relieve pain,restore and improve hmb function and enhance quality of life.

ABSTRACT:Objective To investigate the effect of SDF-1/CXCR7 on inflammatory cytokine synthesis and secretion in gastric cancer SGC-7901 cells.Methods CXCR7 gene in SGC-7901 cells was silenced by shRNA lentiviral vector and the expression of CXCR7 was detected using Western blot and Real-time PCR.There were four groups as follows:LV-shRNA-NC,LV-shRNA-NC+SDF-1,LV-shRNA-CXCR7,and LV-shRNA-CXCR7+SDF-1 groups.Real-time PCR was used to detect the mRNA expressions of TNF-α,IL-1β,IL-6 and IL-8.ELISA was used to detect the protein levels of TNF-α,IL-1β,IL-6 and IL-8 in the culture supernatant.Western blot was used to detect the protein expressions of NF-κB pathway.Results ① Transfection of SGC-7901 cells with CXCR7-shRNA lentiviral vector resulted in a significantly decreased expression of CXCR7 at both mRNA and protein levels (all P<0.01).② Compared with those in LV-shRNA-NC group,IL-6 and IL-8 mRNA expressions and protein levels in the culture supernatant were increased in LV-shRNA-NC+SDF-1 group (P<0.01 )and decreased in LV-shRNA-CXCR7 group (P<0.05).Compared with those in LV-shRNA-NC+SDF-1 group,the expressions of IL-6 and IL-8 at mRNA and protein levels in the culture supernatant were significantly cut down in LV-shRNA-CXCR7+SDF-1 group (P<0.01 ).However,the expressions of TNF-αand IL-1βat mRNA and protein levels in the culture supernatant were not significantly changed by SDF-1 and CXCR7 shRNA.③ The protein expressions of nuclear NF-κB p65,t-IκBαand p-IκBαexhibited no significant differences among the four groups.Conclusion SDF-1/CXCR7 can promote the synthesis and secretion of inflammatory cytokines IL-6 and IL-8 in gastric cancer SGC-7 9 0 1 cells through an NF-κB-independent pathway.

AIM: To study the effect of chronic hypoxic hypercapnia on expression of heme oxygenase-1(HO-1). METHODS: Sprague-Dawley rats were randomly divided into three groups: control group(A),hypoxic hypercapnic group(B), hypoxic hypercapnia+hemin group(C). HO-1 and HO-1 mRNA were observed in pulmonary arterioles by the technique of immunohistochemistry and in situ hybridization. RESULTS: ① mPAP and weight ratio of right ventricle(RV) to left ventricle plus septum (LV+S) were significantly higher in rats of B group than those of A and C group (P0.05). ② Blood CO concentration was significantly higher in rats of B group than that of A group(P

Aim To investigate the effect of ligustrazine on pulmonary arterial pressure,thromboxane A2(TXA2) and prostacyclin(PGI2) in chronic hypoxic hypercapnic rats.Methods Thirty rats were randomly divided into control group(A), hypoxic hypercapnic group(B) and hypoxic hypercapnia+ ligustrazine (lig) group (C) .Results The mPAP in group B was significantly higher than that in group A(P0.05) ; The specific value of WA/TA(vessel wall area/total area) and SMC (the density of medial smooth muscle cells) were significantly higher in group B than that in group A(P0.05).Conclusion Ligustrazine can inhibit pulmonary hypertension and structural remodeling of pulmonary artery in chronic hypoxic hypercapnic rats by inhibiting synthesis of TXA2.

AIM: To investigate the effect of diltiazem on mean pulmonary arterial pressure(mPAP) and nitric oxide synthase(NOS) in arterioles in chronic hypoxic hypercapnic rats. METHODS: Twenty-four rats were randomly divided into three groups: control group(A),hypoxic hypercapnic group(B), hypoxic hypercapnia+ diltiazem group (C), constitutive endothelial NOS(ceNOS) were observed in arterioles of rats using the technique of immunohistochemistry,ceNOS mRNA were observed by the technique of in situ hybridization . RESULTS: (1)mPAP was significantly higher in rats of B group than that of A and C group( P 0 05),but mCAP was lower in rats of C group than that in B group.(2)Light microscopy showed WA/TA (vessel wall area/total area) was significantly lower in rats of C group than that of B group ( P

To investigate the distribution of variant genotypes of Fc gamma receptor IIIa (Fc gamma R IIIa) in healthy Chinese population of Zhengzhou city, genomic DNA was extracted from peripheral blood of healthy donators. The genotypes of Fc gamma R IIIa-158 were determined by nested polymerase chain reaction (PCR) in 137 healthy people in Zhengzhou city. The results showed that frequencies of variant genotypes FF, VV and VF were 42.3%, 48.9% and 8.8% respectively. The distribution of Fc gamma R IIIa-158 in healthy Chinese population of Zhengzhou city was polymorphic and different from that of African Americans (AA) and Caucasian Americans (CA).
Asian Continental Ancestry Group ; European Continental Ancestry Group ; Genotype ; Polymerase Chain Reaction ; *Polymorphism, Genetic ; Receptors, IgG/*genetics ; Variation (Genetics)

ObjectiveTo evaluate the clinical and radiological efficacy of TNFR Ⅱ -Fc combined with methotrexate( MTX ) in treatment of patients with moderate and severe rheumatoid arthritis.MethodsThree hundred and ninty-six RA patients were randomized into the combined treatment group,the TNFR Ⅱ -Fc only group and MTX only group.All patients were treated for 24 weeks.ACR-N,ACR20,ACR50,ACR70,DAS28-ESR and Sharp score of both hands were measured for efficacy,and the side-effects were analyzed by one-way ANOVA.Results After 24-week therapy,the ACR-N of the combined treatment group [( 12.79±9.24)％-year] was significantly improved than that of the TNFR Ⅱ-Fc only group [(9.56±11.16)％-year,P＜0.05] and that of the MTX only group[(5.08±11.10)％-year,P＜0.05],and the TNFR Ⅱ-Fc group was significantly improved than that of the MTX group(P＜0.05).The ACR20 response rate of the combined group(80.4％) was significantly higher than that of the TNFR Ⅱ -Fc group(71.1％,P＜0.05) and the MTX group(56.7％,P＜0.01 ).The ACRS0 response rate of the combined group(53.6％) was significantly higher than that of the MTX group(30.8％,P＜0.01 ).The ACR70 response rate of the combined group was 27.7％,which was significantly different from that of the TNFR Ⅱ -Fc group (15.8％) and MTX group (7.7％,P＜0.05or P＜0.01 ).DAS28-ESR in the combination group was significantly reduced than those of the TNFR Ⅱ -Fc group and MTX group,and the DAS28-ESR of the TNFR Ⅱ -Fc group was significantly reduced than MTX group.The average total Sharp score of both hands,which demonstrated the radiographic changes,was significantly reduced in the combination group than the MTX group(P=0.03).The total adverse events in the combined group(40.9％) was significantly high than that of the MTX group(28.8％,P＜0.05).Conclusion TNFR Ⅱ -Fc combined with MTX can effectively control the activity of RA and radiological progress.