Objective To explore the relationship of pregnancy-associated plasma protein-A (PAPPA),osteoprotegerin (OPG) and endometriosis,so as to apply the new theoretical basis for the etiology of endometriosis.Method PAPP-A and OPG in peritoneal fluid were measured in 25 women with endometriosis(study group) and 25 women with hysteromyoma ablation (control group).Results The levels of PAPP-A and OPG were both higher in peritoneal fluid in study group [(72.3±57.4)U/L and (3.28±2.63) μ g/L]than that in control group [(42.3± 19.7) U/L and (1.73 ±0.45) μ g/L] (P＜0.05).Furthermore,significant correlation was found between the stage of endometriosis and the levels of PAPP-A and OPG in study group (P＜0.05).The concentration of PAPP-A in peritoneal fluid were significantly higher in the secretory phase than the proliferative phase of the menstrual cycle in two groups(P＜0.05) ,and OPG in peritoneal fluid without significant difference(P＞ 0.05).Conclusion PAPP-A and OPG maybe play an important role in the development of endometriosis.

Objective To investigate the effects of Propofol in blood spinal cord barrier (BSCB) disruption induced by spinal cord ischemia reperfusion injury (SCIRI). Methods 72 Japanese white rabbits were randomly assigned into 3 groups: sham-operation group (S); ischemia/reperfusion group (I/R) and Propofol treatment group (I/R + P). The Group S was separated the aorta without cross-clamping. SCIRI was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Propofol was intravenously infused at 10 minutes before aortic clamping and at onset of reperfusion in the Group I/R + P. The Group S and Group I/R were intravenously infused 0.9%sodium chloride. Hind-limb motor function was assessed using Tarlov criteria, and histological observation by histological examination. The permeability of the BSCB was examined using EB as vascular tracers. The expression of MMP-9, claudin-5 and NF-κB were assessed by Western blot, RT-PCR. Results Propofol minimized the neuromotor dysfunction and histopathological deficits and attenuated EB extravasation. In addition, Propofol suppressed SCIRI-induced increase of MMP-9 and NF-κB. Finally, Propofol reduced the loss of claudin-5. Conclusion Propofol stabilizes the BSCB integrity after SCIRI. This beneficial effect is partly mediated by inhibition of MMP-9 and preservation claudin-5 and relates to inhibiting the NF-κB signal pathway.

Objective Kallikrein 4(KLK4) is a glycosylated,chymotrypsin-like serine protease.KLK4 was first isolated from developing enamel by Japanese scientists,later it was discovered that was expressed in the normal and cancerous tissues.Its main function is to play a role in process of the protein hydrosis,resulting in a normal devel-oping or abnormal pathological changes of the organization.This article reviewed the structure,expression,functions, related disease of KLK4 and other aspects.

Objective: To determine the contents of three effective components in Xianlinggubao Capsules. Methods: A RP HPLC was developed for the determination of psoralen, isopsoralen and icariin in Xianlingbao Capsules. Results: The contents of these compoments were 0.93mg/g, 0.95mg/g and 9.2mg/g, respectively. Conclusion: This Methods is simple and reliable.

Objective:To investigate the correlation between polymorphisms of serine hydroxymethyltransferase1 gene and the adverse reactions of high-dose methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL). Methods:A total of 51 patients with ALL were treated with HD-MTX, and clinical manifestations after HD-MTX treatment were evaluated retrospectively. cD-NA was obtained from mRNA. The polymorphisms of SHMT1 gene containing rs1979277, rs3783, rs1979276, and rs12952556 sites were tested by denaturing gradient gel electrophoresis and direct sequencing. Effects of SHMT1 gene polymorphisms on HD-MTX ad-verse reactions were evaluated. Results:Severe adverse reactions in ALL patients treated with HD-MTX appeared to be mainly neutro-penia and hepatoadverse reactions. The frequency distributions of rs3783 (C>G), rs1979276 (C>T), rs12952556 (A>G), and rs1979277 (C>T) were the same. The polymorphisms of rs1979277 showed no correlation with neutropenia (P>0.05) but rs1979277 CT and TT genotypes were correlated with hepatoadverse reactions (CT: OR=0.129, 95% CI: 0.020 to 0.817, P=0.03; TT: OR=0.103, 95% CI:0.017 to 0.620, P=0.013). Conclusion: No correlation was found between the combination of rs1979277, rs3783, rs1979276, rs12952556, and neutropenia, but one or more of these loci may reduce the risk of hepatoadverse reactions.

Objective:To investigate the association between glutathione S-transferase pi (GSTP1) gene polymorphism and toxici-ties related to high-dose methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL). Methods:GSTP1 genotypes and allelic frequencies in 51 children with ALL were determined by Nest PCR, denaturing gel gradient electrophoresis (DGGE), and DNA sequencing. HD-MTX adverse reactions were analyzed using the National Cancer Institute Common Toxicity Criteria (NCICTC). Results:We identified three SNPs of GSTP1, including rs1695 (A313G), rs1138272 (G439T), and rs4891 (T555C). The wild types, het-erozygous types, and homozygous types of GSTP1 rs1695/rs4891 polymorphisms were detected in 32 cases (62.7%), 16 cases (31.4%), and 3 cases (5.9%), respectively. GSTP1 rs1695/rs4891 polymorphisms included only one heterozygous type and one homozygous type. The allele frequencies of the three SNPs were 21.6%, 2.9%, and 21.6%. The AG+GG/TC+CC genotype of GSTP1 rs1695/rs4891 was associated with decrease in the odds of peripheral hemoglobin (OR=0.25, 95%CI=0.06-1.00, P=0.049). The AG+GG/TC+CC genotype of GSTP1 rs1695/rs4891 in standard and intermediate-risk ALL children was significantly correlated with higher odds of gastrointesti-nal toxicity (OR=0.125, 95%CI=0.02-0.78, P=0.026). Conclusion:GSTP1 rs1695 (A313G)/rs4891 (T555C) gene polymorphism is as-sociated with the reduction of peripheral hemoglobin in ALL children and with the odds of gastrointestinal toxicity in standard and inter-mediate-risk ALL children who receive high-dose methotrexate.

In order to quantify the curing effects of phenanthridine on yeast prion, we introduced semi-denaturing agarose gel electrophoresis and fluorescence recovery after photobleaching techniques to quantify the curing effects of phenanthridine on yeast prion at the protein and cellular levels with the [PSI+] yeast strain expressing GFP-Sup35p (NGMC). The results showed that these two approaches could precisely quantify the curing effects of phenanthridine on [PSI+] cells. After a treatment for 1 through 5 days with phenanthridine, the curing rates of [PSI+] cells were 0%, 0%, 51.7%, 87.5% and 94.4%, respectively. Meanwhile, we quantified the sizes of Sup35p polymers in phenanthridine induced pink phenotype cells. The aggregation status in 1-2 days phenanthridine treated cells were similar to those in [PSI+] cells, while the aggregation status in 3-5 days phenanthridine treated cells were similar to those in [psi(-)] cells.
Computer Simulation ; Models, Biological ; Peptide Termination Factors ; metabolism ; Phenanthridines ; pharmacology ; Prions ; drug effects ; genetics ; metabolism ; Saccharomyces cerevisiae ; cytology ; drug effects ; metabolism ; Saccharomyces cerevisiae Proteins ; metabolism

Objective To evaluate the role of spinal nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in hydrogen-induced reduction of inflammatory pain in rats.Methods Sixty-four SPF healthy adult male Sprague-Dawley rats,weighing 200-250 g,were divided into 4 groups (n =16 each) using a random number table:control group (group C),inflammatory pain group (group IP),inflammatory pain plus hydrogen-rich saline group (group IP+H2) and inflammatory pain plus hydrogen-rich saline plus Nrf2 inhibitor all-trans retinoic acid (ATRA) group (group IP+H2+ATRA).Chronic inflammatory pain was induced by injecting complete Freund's adjuvant (CFA) 100 μl into the plantar surface of the left hind paw in IP group and IP+H2 group.The equal volume of normal saline was given instead in group C.Hydrogen-rich saline 5 ml/kg was injected intraperitoneally once a day for 7consecutive days starting from 1 day after injecting CFA in group IP+H2 and group IP+H2+ATRA,and the equal volume of normal saline was given instead in the other groups.ATRA 7 mg/kg was injected intraperitoneally once a day for 2 consecutive days starting from 2 days before injecting CFA.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before establishing the model (T0) and 1,3 and 7 days after establishing the model (T1-3).Six rats were sacrificed after the last measurement of pain threshold on day 7 after establishing the model,and the L4-6 lumbar segments of the spinal cord were removed for determination of the expression of Nrf2,HO-1 and glial fibrillary acidic protein (GFAP) by Western blot.Results Compared with group C,the MWT was significantly decreased and the TWL was shortened at T1-3,and the expression of Nrf2,HO-1 and GFAP was up-regulated in IP and IP+H2 groups (P＜0.05).Compared with group IP,the MWT was significantly increased and the TWL was prolonged at T1-3,the expression of Nrf2 and HO-1 was up-regulated,and the expression of GFAP was down-regulated in group IP+H2 (P＜0.05),and no significant change was found in the parameters mentioned above in group IP+H2+ATRA (P＞0.05).Compared with group IP+H2,the MWT was significantly decreased and the TWL was shortened at T1-3,the expression of Nrf2 and HO-1 was down-regulated,and the expression of GFAP was up-regulated in group IP+H2+ATRA (P＜0.05).Conclusion Activation of spinal Nrf2/HO-1 signaling pathway is involved in hydrogen-induced reduction of infflammatory pain in rats.

Septic shock is the most critical stage of sepsis, and the core of the treatment is improving tissue hypoperfusion.In addition to the improvement of large circulation by fluid resuscitation, the microcirculation also need to be improved, then proper vasoactive drugs should be applied to different types of shock to meet the needs of the body for perfusion.The condition of septic shock progresses rapidly, and the microcirculation in different pathophysiological stages is different, which increases the difficulty of rational use of vasoactive drugs.Monitoring and accurate evaluation of peripheral microcirculation may provide guidance for individualized treatment of septic shock.

Objective To detect the levels of neutrophil extracellular traps (NETs) in patients with antiphospholipid syndrome (APS) and to preliminarily explore its formation mechanism.Methods Plasma samples from 27 APS patients and 30 healthy controls were collected.The circulating free DNA (cf-DNA) in plasma was detected by the PicoGreen nucleic acid quantitative assay kit,and the concentration of citrulline histone 3 (CitH3) was analyzed by enzyme-linked immuno sorbent assay (ELISA).The association of cf-DNA/NETs with thrombotic events in APS patients was further analyzed.The neutrophils in healthy controls were separated by density gradient centrifugation and stimulated with anti-β2GPl/β2GPI complex (100 μg/mL) for 4 h,and the cf-DNA/NETs in the culture supernatant was determined.TLR-4 inhibitor-TAK242 (5 μmol/L) was further used to observe whether the stimulation of the anti-β2GPI/β2GPI complex on cells could be intervened.The differences between groups were analyzed by analysis of variance (ANOVA) or rank sum test,Sidak or Dunnett's test were used to compare the mean of multiple samples and the correlation between variables was analyzed by Spearman's correlation test.Results The concentration of cf-DNA/NETs and CitH3 were significantly increased in plasma of APS patients compared with that in healthy controls [175.7(70.6,205.7) ng/ml vs 29.8(7.6,115.7) ng/ml,Z=-3.654,P＜0.05;19.5(7.8,26.4) ng/ml vs 3.3(0.84,10.3) ng/ml,Z=-3.932,P＜0.05],and there was a significant positive correlation between the cf-DNA/NETs and CitH3 (r=0.447,P=0.019).In the APS group,there was no significant difference in cf-DNA/NETs between patients with arterial thrombosis and those with venous thrombosis [177.1(67.8,297.2) ng/ml vs 184.7(82.4,233.9) ng/ml,Z=-0.301,P=0.786],whereas cf-DNA/NETs in the patients who experienced a new thrombotic event in 1 month was significantly higher than those with a history of thrombosis [192.1(83.6,328.8) ng/ml vs 90.0(42.8,184.7) ng/ml,Z=-2.006,P=0.046].In vitro,anti-β2GPI/β2GPI complex (100 μg/ml) stimulated the release of cf-DNA/NETs from neutrophils,which was significantly increased compared with the control group (t=10.39,P＜0.05),while TAK242 significantly inhibited the stimulating effects of anti-β2GPI/β2GPI complex on cells (t=4.22,P＜0.05).Conclusion The level of cf-DNA/NETs in peripheral blood of APS patients is significantly increased,which may play an important role in APS thrombosis.Anti-β2GPI/β2GPI complex induces the formation of cf-DNA/NETs through TLR4 and participates in the pathological process of APS.