Objective To evaluate the clinical efficacy of domestic bisphosphonates (etidronate and alendronate) in the treatment of postmenopausal osteoporosis. Methods Eighty three patients with postmenopausal osteoporosis were divided randomly into three groups: group Ⅰ(37 cases),group Ⅱ(15 cases) and group Ⅲ(31 cases). Etidronate(400 mg/d) and placebo were given with intermittent cyclical therapy in group Ⅰ and group Ⅲ respectively, and alendronate(10 mg/d) was given continuously in groupⅡ for 9 months. Eeach group was given calcium agents(equal to elementary calcium 500 mg/d). Before and after treatment, the bone mineral density(BMD) was measured by dual energy X ray absorptiometry. The biochemical markers such as blood calcium, phosphate, alkaline phosphatase and urine calcium/creatinin were examined. Results After treatment the BMD of groupⅠ and groupⅡ wee increased obviously(P0.05). The BMD of group Ⅱ was increased more than that of groupⅠ(P

[Objective]To evaluate the results of therapy with knee joint synovectomy or articular irrigation in rheumatoid arthritis.[Method]Thirty-six knees in 32 rheumatoid arthritis patients-according to ARA standard were performed with knee joint synoveetomy and articular irrigation.Twenty-two knees in 20 patients(most in grade Ⅰ)were treated with knee joint cavity irrigation operation combined with intra-articular injection of hyaluronic acid,and 14 knees in 12 cases(most in grade Ⅱ)with knee joint synovectomy,All 32 patients received routine anti-rheumatoid drug therapy preoperatively and postoperatively,and were followed-up for 6 months.All the cases were evaluated by the Lysholm scale.[Result]The early symptoms of all knee joints were improved.The excellent and good result rate of articular irrigation-group was 86.4%,and in synovectomy-group was 85.7%.[Conclusion]Satisfactory results can be obtained through articular irrigation combined with intra-articular rejection of hyaluronic acid and concomitant anti-rheumatoid drug therapy in early-stage of rheonmtoid arthritis,but for mid-stage patients,especially with hyperplasia synovium and deslxoyed cartilage,joint synoveetom should he performed early in order to obtain favoring rehabilitation.

Objective To explore the role of contact system activation in the mechanism of systemic lupus erythematosus (SLE) patients with thrombotic events.Methods A simple sample drawing study was conducted.Sixty-nine patients with SLE admitted to Department of Rheumatism in Tianjin Hospital from June 2014 to February 2016 were enrolled.The patients were divided into simple SLE group (n =38) and SLE + vascular diseases (VD) group (n =31) according to whether the patients complicated with VD or not.The VD patients were subdivided into three subgroups including SLE complicated with myocardial infarction (SLE + MI,n =10),SLE complicated with deep vein thrombosis (SLE + DVT,n =13),and SLE complicated with arterial thrombosis (SLE + AT,n =8).Sixty-eight healthy age and gender-matched volunteers without history of VD were served as controls.Enzyme-linked immunosorbent assay (ELISA) was used to detect the content of FⅫa-C1 inhibitor (FⅫa-C1INH) and FⅫa-antithrombin (FⅫa-AT) in plasma.Flow cytometry was used to analyze the contents of platelets associated factors.The correlation between platelet associated factor and FⅫA-C1INH and FⅫa-AT was analyzed by Spearman correlation analysis.Receiver operating characteristic curve (ROC) was plotted to analyze the predictive value of FⅫA-C1INH and FⅫa-AT for SLE thrombotic events.Results Compared with health control group,the expression of FⅫa-C1INH in plasma in SLE group was significantly decreased [nmol/L:0.00 (0.00,0.07) vs.0.08 (0.03,0.13),P ＜ 0.01],the expression of FⅫa-AT was significantly up-regulated [nmol/L:0.18 (0.07,0.38) vs.0.16 (0.12,0.26),P ＜ 0.05].Compared with the simple SLE group,the expression of FⅫa-C1INH in SLE + DVT and SLE + AT groups was significantly decreased [nmol/L:0.03 (0.02,0.07),0.02 (0.01,0.04) vs.0.07 (0.02,0.11),both P ＜ 0.05],and the expression of FⅫa-AT in plasma in SLE + AT group was significantly increased [nmol/L:0.34 (0.21,0.53) vs.0.17 (0.06,0.30),P ＜ 0.01].It was shown by correlation analysis that FⅫa-C1INH was negatively related with FⅫa-AT in patients with SLE (r =-0.24,P =0.041 6).Activated platelet associated factors such as the production of interferon mediated by transmembrane protein 1 (IFTMI1) and interferon induced by double stranded RNA dependent activation agent (PRKRA) were positively related with up-regulation of FⅫa-AT and down-regulation of FⅫa-C1INH (IFITM1 and FⅫa-AT:r =0.39,P =0.001 2;IFITM1 and FⅫa-C1INH:r =-0.30,P =0.0146;PRKRA and FⅫa-AT:r =0.29,P =0.017 6;PRKRA and FⅫa-C1INH:r =-0.36,P =0.0029).The thrombospondin-1 (TSP-1) and platelet P-selectin were positively related with up-regulation of FⅫa-AT (r1 =0.72,P1 ＜ 0.0001;r2 =0.34,P2 =0.003 8).It was shown by ROC curve analysis that the area under the ROC curve (AUC) for FⅫa-C1INH on evaluating the risk of SLE thrombotic events was 0.998,the sensitivity was 100％,and specificity was 97.4％ when cut-off ＜ 0.01 nmol/L;AUC for FⅫa-AT for evaluating the risk of SLE thrombotic events was 0.954,the sensitivity was 95.0％,and specificity was 84.2％ when cut-off ＞ 0.40 nmol/L;predicted probability of two markers for predicting diagnosis was 0.5,the sensitivity and specificity were both 100％.Conclusions Contact system is activated in patients with SLE.FⅫA-C1INH and FⅫa-AT levels are closely related with platelet associated factors IFITM1 and PRKRA.FⅫA-C1INH and FⅫa-AT can be served as a promising potential biomarker for evaluation of the risk of thrombotic events in SLE.

Objective To study ADFR with statin programmed therapy of osteoporosis in ovariectomized rats.Methods Fifty female rats were randomly allocated into 2 groups:sham operation (S, n =10) and OVX ( n =40) group.After operation for one month,OVX were randomly allocated into 4 groups (each n =10):OVX,statins (T),bisphosphonates (B) and statins+bisphosphonates+calcium+vitamin D (ADFR).After feeding statins or bisphosphonates or ADFR for 100 days,all rats were sacrificed.The effects of T or B or ADFR on bone histomorphology or osteocalcin in sera or deoxypyridoxine in urea were studied.Results The data showed that osteocalcin and deoxypyridine in OVX group were significantly improved compared with S group ( P 0 05) ,in B group was decreased,and in ADFR group was increased compared with OVX group.The histomorphometric date showed that TOS,MOSW,STS/DTS,TBOS,TBSC and iMAR in OVX were significantly increased,and TBV,MLT and ? in OVX were decreased,compared with S group.TBV in B,T and ADFR groups was larger than that in OVX group.TOS,MOSW,TBOS and TBCS in B group were smaller than those in OVX group,? in B group was longer than that in OVX group,TBCS and ? in T group were increased compared with OVX group.Conclusion Statins promote bone turnover,increase osteoblast activity and osteoid production,and reduce the bone construction.Bisphosphonates inhibit bone absorption,while ADFR acelerate bone formation and reduce bone loss,suggesting that polytherapy is preferable to monotherapy.

Bcel-2 family proteins (Bcl-x(L), Bcl-2, Mel-1 etc.) are key regulators of some life processes, including apoptosis and autophagy. They are currently considered as promising targets for developing new anti-tumor therapies. In our study, the human Bcl-2/Bcl-x(L) chimeric gene and the human/mouse Mel-1 chimeric gene were designed and cloned, and the prokaryotic expression vectors for expressing glutathione S-transferase (GST) fusion proteins and histidine tag fusion proteins were constructed respectively. These two proteins as well as the GST-Bcl-x(L) fusion protein were all successfully expressed in E. coli and subsequently purified. In addition, we measured the binding of these Bcl-2 family proteins to the Bid BH3 peptide by fluorescence polarization-based assay. The dissociation constants (Kd) obtained by us were in general agreement with the data reported in literature. The Kd values of all three proteins with or without the GST tag were almost identical. All these results validate the biological functions of these Bcl-2 family proteins obtained by us. These proteins can be used in the experimental screening of small-molecule regulators of Bcl-2 family proteins in vitro.
Escherichia coli ; genetics ; metabolism ; Fluorescence Polarization ; methods ; Glutathione Transferase ; biosynthesis ; genetics ; Humans ; Myeloid Cell Leukemia Sequence 1 Protein ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; genetics ; isolation & purification ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; isolation & purification ; bcl-X Protein ; biosynthesis ; genetics ; isolation & purification

Autophagy is a cellular process in which proteins and organelles are engulfed in autophagosomal vesicles and transported to the lysosome/vacuole for degradation. Protein-protein interactions (PPIs) play a crucial role at many stages of autophagy, which present formidable but attainable targets for autophagy regulation. Moreover, selective regulation of PPIs tends to have a lower risk in causing undesired off-target effects in the context of a complicated biological network. Thus, small-molecule regulators, including peptides and peptidomimetics, targeting the critical PPIs involved in autophagy provide a new opportunity for innovative drug discovery. This article provides general background knowledge of the critical PPIs involved in autophagy and reviews a range of successful attempts on discovering regulators targeting those PPIs. Successful strategies and existing limitations in this field are also discussed.

Polyoxin is a group of structurally-related peptidyl nucleoside antibiotics bearing C-5 modifications on the nucleoside skeleton. Although the structural diversity and bioactivity preference of polyoxin are, to some extent, affected by such modifications, the biosynthetic logic for their occurence remains obscure. Here we report the identification of PolB in polyoxin pathway as an unusual UMP C-5 methylase with thymidylate synthase activity which is responsible for the C-5 methylation of the nucleoside skeleton. To probe its molecular mechanism, we determined the crystal structures of PolB alone and in complexes with 5-Br UMP and 5-Br dUMP at 2.15 Å, 1.76 Å and 2.28 Å resolutions, respectively. Loop 1 (residues 117-131), Loop 2 (residues 192-201) and the substrate recognition peptide (residues 94-102) of PolB exhibit considerable conformational flexibility and adopt distinct structures upon binding to different substrate analogs. Consistent with the structural findings, a PolB homolog that harbors an identical function from Streptomyces viridochromogenes DSM 40736 was identified. The discovery of UMP C5-methylase opens the way to rational pathway engineering for polyoxin component optimization, and will also enrich the toolbox for natural nucleotide chemistry.
Bacterial Proteins ; chemistry ; Crystallography, X-Ray ; Methyltransferases ; chemistry ; Protein Domains ; Protein Structure, Secondary ; Pyrimidine Nucleosides ; biosynthesis ; Streptomyces ; enzymology