Costimulatory signals have become a hot field in immunological researches. As co-inhibitory molecules, programmed death-1 ( PD-1) and its ligands (PD-1/PD-L) have been demonstrated to play an important role in autoimmune disease, organ transplant rejection, microorganism infection, tumor immune escapes etc. . In recent years,some studies about PD-1/PD-L pathway in ophthalmology have been curried out and reported. Some changes were found in PD-1/PD-L pathway, such as ocular immunologic diseases, ocular infectious diseases, ocular tumors, immune privilege in ocular tissues and so on. Through the research on PD-1/PD-L pathway,we can further understand the pathogenesis of some ocular diseases and find new methods for their prevention and treatments. This article reviewed the recent advances in PD-1/PD-L pathway in ophthalmological physiopathology.

Background Research determined that hypoxia inducible factor-1(HIF-1)is associated with the hypoxia response in normal organ,and it plays an important role during the embryon development.It is also proved that the expression of vascular endothelial growth factor(VEGF)is upregulated in embryon retina.But,whether the action of HIF-1 and VEGF is correlated is unclear. Objective The aim of this study was to investigate the dynamic change of expression of HIF-1α and VEGF in retina during embryonic development and explore the role of HIF-1α and VEGF along with retinal evolvement.Methods The different embryon ages of SD rats were obtained from 30 clean pregnant SD rats by cesarean surgery.The retinas were isolated from embryon 10一day,12一day,14-day,16-day and 20-day rats respectively.The expressions of HIF-1 α and VEGF protein in retina were semi-quantitatively and qualitatively determined by immunochemistry,and the expressions of HIF-l α and VEGF mRNA in retina with different-embryon-phase and adult rats were detected by RT-PCR. Results The hishly level of expression of HIF-1 α and VEGF protein were found in the cellular nuclei and cytoplasm of retina in embryon 10一and 12-day rats.With the increase of embryon age.the expression of HIF-1α and VEGF protein in retina lowed(F=56.70,P<0.01；F=60.78.P<0.01).Compared with the adult rats,the expressions of HIF-1α and VEGF protein in retina were higher from embryon 0-day through 20-day rats(all P<0.01).The significantly positive correlation was found in the expression level between HIF-1α and VEGF protein throughout the experimental duration(r=0.96,P=0.00).Followed the same pattern,the expression levels of HIF-1α and VEGF mRNA in retinas were also enhanced in the embryon 10- and 12-day rats.Identically,a gradually weakened trend was seen in the expressions of HIF-1 α and VEGF mRNA in retinas as the increase of gestational age of rats(F=68.84,P<0.01；F=96.49,P<0.01),and the exDressions of HIF-1 α and VEGF mRNA decreased in the adult rats compared with different embryon-phase rats,showing a statistically significant difference between them(all P<0.01). Conclusion The expressions of HIF-1 αand VEGF in retina appear a dynamic alteration from hish to low during the embryonic development of rat retina,indicating that HIF-1α/VEGF pathway might participate in the process of embryo development of rat retina.

Humans ; Lung Neoplasms ; therapy ; Medicine, Chinese Traditional ; methods ; trends

OBJECTIVE:To observe the effects of alprostadil combined with papaverine on blood coagulation indexes and complications in uremic hemodialysis patients after initial arteriovenous fistula.METHODS:One hundred and eighteen uremic hemodialysis patients undergoing initial arteriovenous fistula in our hospital during Feb.-Jun.2015 were divided into control group and observation group according to random number table,with 59 cases in each group.Both groups received local irradiation with hemodialysis internal fistula repair instrument 30 min,tid,from 3 days before surgery to 10 days after surgery.Control group was treated with Alprostadil injection 10 μg,iv,qd,immediately after surgery.Observation group was additionally treated with Papaverine in jection 30 mg,iv,qd,on the basis of control group.Both groups received treatment for 10 d.The orificium fistulae blood flow,hemodialysis blood flow and the time of initial hemodialysis were compared between 2 group.The plasma prothrombin time (PT),activated partial thromboplastin time (APTT),fibrinogen (Fib),platelet count (PLT) and C-reactive protein (CRP) levels were observed in 2 groups before and after surgery.The occarrence of postoperative complications was observed.RESULTS:The orificium fistulae blood flow and hemodialysis blood flow of observation group were significantly higher than those of control group,and ini tial hemodialysis time was significantly shorter than control group,with statistical significance (P＜0.05).Before surgery,there was no statistical significance in PT,APTT,Fib,PLT and CRP between 2 groups (P＞0.05).After surgery,APTT and CRP of 2 groups were increased significantly,Fib was decreased significantly;the above indexes of observation group was significantly better than that of control group,with statistical significance (P＜0.05).There was no statistical significance in PT,PLT between 2 groups (P＞0.05).There was no statistical significance in the incidence of internal fistula infection and postoperative wound bleeding volume＞ 10 mL between 2 groups (P＞0.05).The incidence of internal fistula occlusion and orificium fistulae thrombus in observation group were significantly lower than control group,with statistical significance (P＜0.05).CONCLUSIONS:The application of alprostadil combined papaverine on uremic hemodialysis patients after initial arteriovenous fistula can effectively prevent inflammation reaction,fistula thrombus formation and fistula occlusion,and improve the maturation of fistula.

BACKGROUND:Establishing the animal model of membranous nephropathy is of importance to figure out the pathogenesis of membranous nephropathy.
OBJECTIVE:To investigate the expression of nephrin and podocin in the model of membrane nephropathy in rats, and to investigate their relationships with the pathogenesis of membranous nephropathy.
METHODS:A total of 40 Sprague-Dawley rats were equivalently randomized into model and control groups. Rats in the model group were in premunity by given subcutaneous and multi-point injection of 1 mg cationic bovine serum albumin firstly dissolved in 0.5 mL normal saline and then ful y emulsified with the equal incomplete Freund’s adjuvant for 1 week, and 16 mg/kg cationic bovine serum albumin was injected via vein tails, once every other day for 4 weeks. The same volume of normal saline was injected into the controls. The mRNA expressions of nephrin and podocin in renal tissues were detected using real-time PCR, and biochemical indicators and morphological observation were measured at 2 and 4 weeks after modeling.
RESULTS AND CONCLUSION:(1) In the model group, the total amount of urine and serum albumin levels were significantly decreased accompanying with overt proteinuria, and the serum creatinine, urea nitrogen, cholesterol and triglyceride levels were significantly increased al in a time-independent manner compared with the control group (P<0.01), and the difference was significant (P<0.05). (2) The pathological examination showed that rats in the model group had different degrees of renal tubular dilatation, glomerular basement membrane thickening, mesangial cel s and stromal hyperplasia, which was typical of membranous nephritis. (3) Moreover, the mRNA expressions of podocin and nephrin in the model group were lower than those in the control group. (4) In conclusion, the decreased expressions of podocin and nephfin may disturb the integrity of the slit membrane of podocytes giving rise to the damage of glomerular filtration barrier, and proteinuria appears in final.

Objective To study the effect of siRNA targeting bcl-2 gene on the drug-sensitivity of HL-60 cell to homoharringtonin(HT). Methods siRNA, selected by previous experiments and packaged with lipofectamine 2000, was transferred into HL-60 cells. Six hours later, the cells were cultured with homoharringtonin. The cell growth of HL-60 cells was detected by MTT methods at 24, 48, 72 hours respectively. The level of bcl-2 protein and ROS (reactive oxygen species, ROS) as well as membrane potential of mitochondrion was determined by flowcytometry. Results The siRNA could significantly increase the inhibitive effect of homoharringtonin on growth of HL-60 cells. The combination of siRNA with homoharringtonin resulted in the falling of bcl-2 protein level and rising of ROS level as well as descending of membrane potential of mitochondrion of HL-60 significantly (P

Objective:Investigating the expression of HIV-1 co-receptors CXCR4,CCR5 and chemoking SDF-1 in human placentae and trophoblasts is to explore the mechanism of in-utero transmission of human immunodeficiency virus type 1(HIV-1).Methods:Using semi-quantitative reverse transcriptase-polymerase chain reaction,detected the transcripts of CXCR4,CCR5 in placenta tissues and trophoblasts.Immunocytochemistry and immunohistochemistry analysis revealed the expression of CXCR4,CCR5 in primary cultured first trimester trophoblasts and villous tissue.Also the expression of SDF-1 in villi of first trimester,and the presence of SDF-1 in the culture of isolated trophoblasts were examined by in situ hybridization,immunohistochemistry and enzyme-linked immunosorbent assay.Results:CXCR4 and CCR5 mRNA were detected in placentae of various gestational phases and in first trimester trophoblasts.However,primary cultured trophoblasts were found to be reactive only with antibodies against CXCR4.In the villous tissue sections,CXCR4 was found in trophoblasts,while CCR5 in stromal cell and/or Hofbauer cell.First trimester trophoblasts expressed SDF-1 strongly and secreted SDF-1 in vitro.Conclusion:CXCR4 and CCR5 were expressed in placentae.Hence,they maybe involved in in-utero transmission of HIV-1 as co-receptors.However,SDF-1 expressed in trophoblasts may protect fetus from being invaded by X4-HIV-1.R5-HIV-1 may infect CCR5+ stromal cells and/or Hofbauer cells through placental disruptions.

Objective To observe the expression of uPA, tPA and PAI-1 in whole blood of rat membranous ne-phropathy ( MN) models induced by cationic bovine serum albumin ( C-BSA) , and to explore the effect of fibrinolytic sys-tem on podocyte apoptosis and pathological changes. To explore the possible preventive and therapeutic effects and the pos-sible mechanisms of early prevention of fibrinolysis. Methods We developed a MN model with the modified Border meth-od. At the end of the 1st, 2nd, 3th, and 4th week of immunization, respectively, the levels of whole blood uPA, tPA and PAI-1 were determined by ELISA. The rat kidney tissues were examined by light microscopy and electron microscopy to i-dentify the pathological changes. The expression levels of nephrin and WTl were detected with immumofluorescence staining and their correlation was analyzed. Results Compared the treatment group with control group, the levels of whole blood uPA, tPA and PAI-1 of the model group were decreased, while PAI-1 was elevated, showing a significant difference ( P<0. 05). The degree of renal interstitial fibrosis was more serious. Correlation analysis showed that the whole blood tPA and uPA levels were positively correlated with the changes of nephrin protein expression in the kidney tissue, while the whole blood PAI-1 level was negatively correlated with the nephrin protein expression in the kidney tissue. Conclusions In the process of MN development, the fibrinolytic system may have important significance for podocyte apoptosis. Determination of early phase of MN podocyte injury may be another therapy target for prevention of the disease development, and then pro-vide new ideas for clinical research and drug development for MN.

This study examined the cytotoxicity of a new implant material modified by microarc oxidation technique. Cells on different surfaces of the implant were evaluated 2, 4 and 6 days after treatment. The results showed that cell attachment, cell morphology, and cell proliferation were influenced by the different surface treatments, and a significant increase in the osteoblast cell activity was observed on the porous MAO-Ti coating. Our results suggest that the porous MAO-Ti surface has a better biocompatibility and electrochemical performance than pure titanium surface.

Outpatient care services are usually the patient's first contact between the patients and the most bas-ic health care. The provision of outpatient care contributes to immediate and large gains in health status. The pay-ment method is one of the most common incentive methods applied by purchasers to guide the performance of outpa-tient care providers. This systematic review applied cochrane review method, and searched, screened, assessed and synthesized the relevant original studies. 19 studies were finally included. It was found that existing payment methods combined with P4 P interventions could probably slightly improved the health professionals' use of some tests and treat-ments ( adjusted RR median = 1 . 095 , range 1 . 01 to 1 . 17 ) , but may have led to little or no difference in patients' utilisation of health services ( adjusted RR median = 1 . 01 , range 0 . 96 to 1 . 15 ) and may have led to little or no difference in the control of blood pressure or cholesterol ( adjusted RR = 1 . 01 , range 0 . 98 to 1 . 04 ) . Pay for per-formance involves a complex design, each detail design may contain different incentive effect, therefore policy makers intend to apply pay-for-performance to guide the behavior of health providers, the design on each components of pay for performance should be analyzed in order to find more potential intervention points.