BACKGROUND:Mesenchymal stem cells are capable of self-renew,a high degree of proliferation,with multi-differentiation potential,low immunogenicity and immunomodulatory properties.Both in vivo and in vitro it is able to regulate allogeneic immune response,to induce immune tolerance.In the solid organ transplantation it is playing an increasingly important role.OBJECTIVE:To summarize the research progress on the immunomodulatory mechanism and application of mesenchymal stem cells in solid organ transplantation.METHODS:An online search of Pubmed was undertaken by using the key words of "Mesenchymal Stem Cells,Mesenchymal Stem Cell Transplantation,Organ Transplantation,Transplantation Immunology,Immunologic Graft Enhancement,Graft vs.Host Disease" in Mesh to identify the relevant articles published in English from January 1994 to October 2009.At the same time,Wanfang database was screened to identify the relevant articles published between January 1994 and October 2009 with the key words of "Mesenchymal Stem Cells,Organ Transplantation,Transplantation Immunology" in Chinese.Inclusive criterion:The articles related to the immunomodulatory properties,transplantation immunology and application of mesenchymal stem calls in the solid organ transplantation were included.Exclusive criterion:The articles with repetitive research or Meta analysis were excluded.RESULTS AND CONCLUSION:Totally 200 relevant articles were selected and 86 of them met the inclusive criterion.Mesenchymal stem cells exhibit low immunogenicity and immunomodulatory properties,have an indispensable advantage about inducing graft tolerance and repairing tissue in solid organ transplantation.The mechanism of inducting immune tolerance may be related to soluble factors,regulatory T cells,tolerant dendritic cells,bone marrow chimerism,anti-inflammatory and tissue repair,dose and time of injecting MSCs.

Objective: Enhanced expression of adhesion molecules on synovial tissu e has been demonstrated in patients with dialysis-related amyloidosis (DRA). T he study was conducted to elucidate the mechanisms by which the expression of adh esion molecules on synovial cells was up-regulated.Methods: Human type-B synov ial cells were cultured in vitro with β2-microglobulin modified with adva nced glycation end products (AGE-β2m) , native β2-microglobulin (β2 m) , tumor necrosis factor-α（TNF-α）and interleukin -1β（ IL-1β）. The expression of intercellular adhesion molecule-1(ICAM-1), vasc ular cell adhesion molecule-1(VCAM-1), and E-selectin was examined by immunofluor esc enct staining and flow cytometer analysis. Results:ICAM-1 and VCAM-1, but not E -selectin, were constitutively expressed on human type-B synovial cells. TNF -α a nd IL-1β enhanced the expression of ICAM-1 and VCAM-1 in a dose- and time - depen dent manner. Neither of these cytokines appeared to induce the expression of E - selectin. Both β2m and AGE-β2m had no direct effect on the expression of the a dhesion molecules.Conclusion: Elevated level of IL-1β and TNF-α in the synov ial tissue may up-regulate the expression of adhesion molecules on synovial cel ls and therefore promote local monocytes infiltration.

Objective The study was performed to determined the significance and safety of liver biopsies in these patients as a pre-transplantation screening test. Methods From January 1999 to August 2002, seventy-four renal transplant recipients with hepatitis B or C virus infection were received the percutaneous liver biopsy. The severity of liver inflammation(G) and fibrosis(S) were evaluated by semi-quantity technique. The patients whose liver histological diagnosis was G 0-2 S 0-2 received renal transplantation(n=31). Patients with hepatitis B or C virus infection who received renal transplantation in the period of January 1995 to December 1998 were selected as historic controls. Normal level of serum transaminase was considered as a indication for the received renal transplantation during this period. The incidence of liver dysfunction after transplantation was compared between the two groups. Results It showed among thirty-one patients received renal transplantation from 1999-2002, only 1 patient (3.2%) developed liver failure after transplantation. However, among 60 patients of historic control, 17 (23.8%) suffered from liver dysfunction (P

Objective To evaluate the relationship between NK cytotoxicity and anemia in uremia. Methods The effect of rHuEPO on natural killer (NK) cell cytotoxic activity was studied in 12 hemodialysis(HD) patients. Results The levels of hemoglobin (Hb) and NK cell activity were significantly lower in HID patients than that in healthy controls. After two months of the treatment with rHuEPO, the levels of Hb in these patients rose significantly with a parallel rise in NK cell activity. NK cell activity was not increased when they were incubated with rHuEOP but was increased with red blcxxl cells. Conclusion Improved NK cell cytotoxicity in HD patients after treatment with rHuEPO was achieved through the rise in R15C rather than through rHuEPO itself.

Objective To determine the expression of advanced glycation end products(AGE) binding proteins on human joint synovial cells for elucidating the pathobiological effects of ?2m modified with AGE(AGE-?2m) on joint resident cells. Methods Type A and type B synovial cells were isolated and cultured in vitro. The expression of AGE receptor 1 (ACE-R1 ), AGE receptor 2 (AGE-R2), AGE receptor 3 (AGE-R3) and 35 KD receptor for AGE(RAGE) on synoviocytes were detected by immunofluorescent staining using specific antibodies and flow cytometric analyses. mRNA of AGE receptors was examined by RT-PCR techniques.-Results RAGE and AGE-R3, but not AGE-R1 and AGE-R2, were constitutively expressed on the membrane surface of both type A and type B synovial cells. These two types of synovial cell also expressed mRNA of RAGE and AGE-R3. Conclusion Human joint synovial cells express specific AGE binding proteins, RAGE and AGE-R3, suggesting that these cells may be involved in AGE metabolism and might be the target of the biological effects of AGEs in dialysis-related amyloidosis.

To elucidate the effects of pro inflammatory mediators on mRNA expression of AGE receptors in type B synovial cells, type B synovial cells from normal subjects were isolated and cultured in vitro with human serum albumin modified with advanced glycation end products (AGE HSA), tumor necrosis factor ?(TNF ?)and interleukin 1?(IL 1?). The expression of RAGE mRNA and AGE R3 mRNA was examined by RT PCR techniques. TNF ?, AGE HSA and IL 1? up regulated the expression of AGE R3 mRNA in type B synovial cells in a dose and time dependent manner. In contrast, TNF ? and AGE HSA down regulated the expression of RAGE mRNA in a dose and time dependent manner. IL 1? had no effect on RAGE mRNA expression. The regulatory responses induced by AGE HSA were blocked by a neutralizing polyclonal anti human TNF ? antibody, suggesting that the effects of AGE HSA were mediated by TNF ?. The proinflammatory mediators may regulate the gene expression of AGE receptors in type B synovial cells, and the regulatory role of these receptors is different in response to the proinflammatory mediators.

The purpose of this study was to explore the incidence of tuberculosis (TB) in chronic renal failure (CRF) patients with or without renal replacement therapy and to evaluate the effect of chemoprophylaxis on incidence of active TB. A total of 3360 CRF patients from April 1989 to Sept. 2002 were enrolled in this study. Chemoprophylaxis for TB was given to the patients with increased serum anti PPD IgG levels from Jan. 1995 to Sept. 2002. The prevalence of active TB during this period was compared with that of the historical control group from April 1989 to Dec. 1998 (without prophylaxis). The results showed that the overall incidence of active TB in all patients was 2 4% (82/3360). Extrapulmonary TB was the most common feature (75 6%) with the major infective sites in pleura (20 7%) and lymph node (17 7%). There were 58 5% patients with active TB showing increased serum and/or serous exudate anti PPD IgG levels and 24 2% patients showing positive TB bacillus DNA (PCR). The total incidences of TB (1 76%) and disseminated TB (2 3%) in the chemoprophylaxis group were significantly lower than those in the non chemoprophylaxis group (4 1% and 7 5%, respectively, P

Adefovir dipivoxil (ADV) is commonly used as an anti-viral agent in the treatment of chronic hepatitis B,with a dose-and time-dependent nephrotoxicity.Clinical analysis was made in 4 patients with chronic hepatitis B who developed Fanconi syndrome and hypophosphatemic osteomalacia after long-term use of ADV (10 mg/d).

Objective Streptococcus sanguis is a possible candidate bacterium for the caries replacement therapy, which has no advantages in the acidic environment.The aim of the study was to construct acid-resistant strains of Streptococcus sanguis, determine its acid tolerance, and explore the mechanism of its antagonism against Sterptococcus mutans.Methods By gradually reducing the pH value of the medium, we constructed acid-resistant strains of Streptococcus sanguis, observed their growth and measured their acid tolerance according to their survival rate against lethal pH.We evaluated the competitive relationship between Streptococcus sanguis and Streptococcus mutans by plate experiment and detected the changes of related acid resistance genes by real-time quantitative PCR.Results The growth of Streptococcus sanguis and its acid-resistant strains were limited by the pH value, and that of Streptococcus sanguis was better in either acidic or normal environment.The lethal pH value of Streptococcus sanguis was 3.6, that of its acid-resistant strains was 2.3, and the survival rate of the acid-resistant strains was 66.59% in the pH 3.6 environment.In comparison, the lethal pH value of Streptococcus mutans was 2.5, that of its acid-resistant strains was 2.1, and the survival rate of the acid-resistant strains was 2.55% in the pH 2.5 environment.In the presence of chloramphenicol, the acid-resistant strains could not survive in the original lethal pH.In the sub-lethal pH environment, the expressions of the acid resistance-related genes Groel and Dnak in the acid-resistant strains were significantly up-regulated as compared with those in the original Streptococcus sanguis (P<0.05).Conclusion Streptococcus sanguis has an acid adaptability and can enhance acid resistance in the sub-lethal pH environment.Acid-resistant Streptococcus sanguis in the replacement therapy may provide some new ideas for the treatment of dental caries.

Objective: To assess trends of β-blocker use within 24h of admission in ideal candidates with acute myocardial infarction (AMI) in eastern urban China from 2001 to 2011. Method: A 2-stage random sampling design was performed. In the first stage, a simple random-sampling was used to identify participating hospitals. In the second stage, a systematic sampling was conducted in 2001, 2006 and 2011 to select cases from the participating hospitals. Data was obtained by central medical record abstraction. 10-year trend and predictors of early β-blocker application were assessed with weighted calculation for each year to represent the overall situation of eastern urban China. Results: 35 hospitals were sampled and 32 of them were finally participated. With necessary exclusion, 1399 ideal candidates were included in this analysis. The early weighted β-blocker application rates in 2001, 2006 and 2011 were 64.7%, 69.7%, and 60.9% respectively, P=0.0447 for trend. Patients with chest pain at admission (OR=2.22, 95% CI 1.19-4.13), higher systolic blood pressure (OR=1.40, 95% CI 1.11-1.77) or faster heart rate (OR=2.01, 95% CI 1.58-2.55) were more likely to use β-blocker; in contrast, compared with NSTEMI patients, STEMI patients seemed less likely to receive such treatment (OR=0.55, 95% CI 0.37-0.81). Conclusion: The early β-blocker therapy in eastern urban China is suboptimal for ideal AMI patients who could benefit from it. The application pattern has not been changed from 2001 to 2011 which might be related to physicians' misunderstanding of relevant evidence or guidelines. Our study may help to create an important target to improve the quality of AMI care.