Clinical efficacy of rituximab for acute rejection in kidney transplantation: a meta-analysis.

OBJECTIVES: This meta-analysis was undertaken to compare the efficacy and safety of pretransplant treatment with rituximab in sensitized patients receiving kidney transplantation. METHODS: PubMed, EMBASE, and Cochrane databases were searched to identify studies that used pretransplantation rituximab in eligible patients. The major outcomes included antibody-mediated rejections (AMR) after kidney transplantation and one-year graft survival rate. The meta-analysis was performed using fixed-effects model. RESULTS: Seven studies were identified including a total of 589 patients, of whom 312 were treated without rituximab, while 277 were treated with rituximab. In our meta-analysis, patients treated with rituximab had significantly fewer AMR after kidney transplantation [odds ratio (OR) 0.52, 95 % CI 0.28, 0.98, P = 0.04] and higher rate of one-year graft survival rates (OR 3.02, 95 % CI 1.14, 8.02, P = 0.03), indicating that rituximab is effective against acute rejection and enhances graft survival in kidney transplantation. No differences were noted in other efficacy and safety parameters in these two patient groups. CONCLUSIONS: We demonstrated that preinduction with rituximab could significantly improve AMR and graft survival rates in sensitized patients undergoing kidney transplantation. Future prospective controlled studies are warranted to further understand rituximab's role in kidney transplantation.

Dynamic expression changes between non-muscle-invasive bladder cancer and muscle-invasive bladder cancer.

AIMS AND BACKGROUND: Despite elaborate characterization of the risk factors, bladder cancer is still a major epidemiological problem whose incidence continues to rise each year. We aim to investigate the dynamic expression changes between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). METHODS: The gene expression profile GSE13507 was obtained from the Gene Expression Omnibus, and the R package was used to identify gene expression signatures (GESs) between NMIBC and MIBC. Gene ontology enrichment analysis was performed for GES function analysis. We used miRTarBase and TargetScan to identify the differentially regulated microRNAs, and TfactS to identify transcription factors between NMIBC and MIBC. Bionet was used to identify the differentially expressed subnetwork. RESULTS: A total of 802 upregulated NMIBC GESs and 668 downregulated MIBC GESs were identified. Functional enrichment analysis revealed that the MIBC GESs were majorly involved in cell cycle and inflammatory response. miR-29c and miR-9 were regarded as key microRNAs in MIBC. SMAD3 in MIBC and SMAD5 and SMAD7 in NMIBC were potential activated transcription factors. In addition, a subnetwork that was considered to capture the differences between MIBC and NMIBC was identified, of which GRB2 and UBC were the hub nodes. CONCLUSIONS: Some key microRNAs, activated transcription factors and hub nodes have been identified in this study, which may be used as potential biomarkers or targets for the diagnosis, treatment and detection of bladder cancer at different stages.

The association between fish consumption and risk of renal cancer: a meta-analysis of observational studies.

BACKGROUND: Several case-control studies and cohort studies have investigated the association between fish intake and renal cancer risk, however, they yielded conflicting results. To our knowledge, a comprehensive assessment of the association between fish consumption and risk of renal cancer has not been reported. Hence, we conducted a systematic literature search and meta-analysis to quantify the association between fish consumption and renal cancer. METHODS: A systematic search was performed using the PubMed, Embase, and Cochrane Library Central database for case-control and cohort studies that assessed fish intake and risk of renal cancer. Two authors independently assessed eligibility and extracted data. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Subgroup analyses, sensitivity analysis and cumulative meta-analysis were also performed. RESULTS: A total of 12 case-control studies and three cohort studies published between 1990 and 2011 were included in the meta-analysis, involving 9,324 renal cancer cases and 608,753 participants. Meta-analysis showed that fish consumption did not significantly affect the risk of renal cancer (RR=0.99, 95% CI [0.92,1.07]). In our subgroup analyses, the results were not substantially affected by study design, region, gender, and confounder adjustments. Furthermore, sensitivity analysis confirmed the stability of results. CONCLUSIONS: The present meta-analysis suggested that there was no significant association between fish consumption and risk of renal cancer. More in-depth studies are warranted to report more detailed results, including stratified results by fish type, preparation method, and gender.

[Spectroscopy analysis of sulfonated poly (arylene ether ketone sulfone) on side chain for proton exchange membrane].

A series of poly (arylene ether ketone sulfone) s containing different amino content (Am-PAEKS) were prepared via direct polycondensation reactions, and then the sulfobutyl groups were grafted onto the Am-PAEKS by amidating reaction between the amide groups in Am-PAEKS and carboxylic acid groups in 4-(N-butane sulfonic) aminobenzoic acid. The structures of the compounds and the polymer were confirmed by FTIR and H-NMR. The new characteristic bands at 1 239 and 1 060 cm(-1) were assigned to O=S=O symmetric stretching vibration and asymmetric stretching vibration of the sulfonic groups in sulfonated poly (arylene ether ketone sulfone) on side chain (S-SPAEKS), and the structures of the polymers were further confirmed by 1H NMR spectra, and the proton peak at 1.64 ppm was assigned to the methyl in the middle of the pendant sulfonated aliphatic side chains, which show that the S-SPAEKS had been prepared successfully. In TGA curves we can observe two distinct weight loss steps, the first step was mainly attributed to the splitting-off of the sulfonic acid groups at 300 degrees C, and the second step was mainly attributed to the decomposition of the main chain of the S-SPAEKS at 450 degrees C. This series of SSPAEKS polymers exhibit excellent thermal properties by thermo gravimetric analysis, which can satisfy the basic requirements of proton exchange membrane (PEM) for fuel cells.

Choice of approach for hepatectomy for hepatocellular carcinoma located in the caudate lobe: isolated or combined lobectomy?

AIM: To investigate the significance of the surgical approaches in the prognosis of hepatocellular carcinoma (HCC) located in the caudate lobe with a multivariate regression analysis using a Cox proportional hazard model. METHODS: Thirty-six patients with HCC underwent caudate lobectomy at a single tertiary referral center between January 1995 and June 2010. In this series, left-sided, right-sided and bilateral approaches were used. The outcomes of patients who underwent isolated caudate lobectomy or caudate lobectomy combined with an additional partial hepatectomy were compared. The survival curves of the isolated and combined resection groups were generated by the Kaplan-Meier method and compared by a log-rank test. RESULTS: Sixteen (44.4%) of 36 patients underwent isolated total or partial caudate lobectomy whereas 20 (55.6%) received a total or partial caudate lobectomy combined with an additional partial hepatectomy. The median diameter of the tumor was 6.7 cm (range, 2.1-15.8 cm). Patients who underwent an isolated caudate lobectomy had significantly longer operative time (240 min vs 170 min), longer length of hospital stay (18 d vs 13 d) and more blood loss (780 mL vs 270 mL) than patients who underwent a combined caudate lobectomy (P < 0.05). There were no perioperative deaths in both groups of patients. The complication rate was higher in the patients who underwent an isolated caudate lobectomy than in those who underwent combined caudate lobectomy (31.3% vs 10.0%, P < 0.05). The 1-, 3- and 5-year disease-free survival rates for the isolated caudate lobectomy and the combined caudate lobectomy groups were 54.5%, 6.5% and 0% and 85.8%, 37.6% and 0%, respectively (P < 0.05). The corresponding overall survival rates were 73.8%, 18.5% and 0% and 93.1%, 43.6% and 6.7% (P < 0.05). CONCLUSION: The caudate lobectomy combined with an additional partial hepatectomy is preferred because this approach is technically less demanding and offers an adequate surgical margin.

[Role of the activation of interleukin-6/STAT3 in cholangiocyte proliferation induced by cold ischemia reperfusion and injury].

OBJECTIVE: To investigate the role of IL-6/STAT3 pathway in the proliferation of cholangiocyte induced by cold ischemia and reperfusion injury. METHODS: Rats were randomized into CP 1 h and CP 12 h groups (supplied livers were preserved for 1 or 12 h), anti-IL-6R (rats in CP 12 h group were administrated with anti-rat soluble IL-6 receptor antibody), and control group. At 1, 3, 7, 14 d postoperative, IL-6 concentration in liver homogenate and cholangiocyte proliferation were detected by enzyme linked immunosorbent assay and histochemistry respectively. Expressions of IL-6 mRNA, phosphorylated-STAT3 and cyclin D1 protein in cholangiocytes were determined by real-time PCR or Western blot analysis. Serum concentrations of ALP and GGT and histology analysis were also performed. RESULTS: Minimal expressions of IL-6, p-STAT3 and cyclin D1 were detected in CP 1 h group, with a slight cholangiocytes proliferation. Cholangiocytes responded to extended cold preservation with severe bile duct injures and marked increase in IL-6 secretion, p-STAT3 and cyclin D1 protein expression, followed by compensatory cholangiocytes regeneration. Parallel to this observation, biochemical index and morphology indicated that bile duct injury was recovery at 14 d postoperative. However, anti-sIL-6R inhibited cholangiocytes proliferation and reduced the expressions of IL-6, STAT3 and cyclin D, with the cellular injury and increase of serum ALP or GGT. CONCLUSIONS: IL-6/STAT3 pathway might participate to initiate cholangiocytes regeneration after cold ischemia and preservation injury, which might benefit biliary recovery after liver transplantation.

[Role of IL-6/STAT3 in rat cholangiocyte proliferation induced by lipopolysaccharide].

OBJECTIVE: To investigate whether lipopolysaccharide (LPS) stimulates cholangiocyte proliferation via the IL-6/STAT3 pathway in vivo. METHODS: Rats were randomized into three groups: LPS group (injected intravenously with LPS 2.5 mg/kg), anti-IL-6 group (injected intravenously with anti-IL-6 0.5 mg/kg 1hr after LPS injection), and control group. At 6, 12, 24, 48 and 72 h after LPS injection, LPS concentration in plasma was detected by kinetic turbidimetric limulus test. IL-6 concentrations in liver homogenate was determinded by ELISA, cholangiocyte proliferation was checked by immunohistochemistry, expression of IL-6 mRNA was quantified by real-time RT-PCR, the level of phophorylated-STAT3 (P-STAT3) protein was analyzed by western blotting. RESULTS: Cholangiocytes responded to LPS by a marked increase in cell proliferation, IL-6 secretion and P-STAT3 expression. Anti-IL-6 neutralizing antibody inhibited LPS-induced cholangiocytes proliferation, and decreased levels of IL-6 and p-STAT3. CONCLUSIONS: LPS promotes cholangiocyte proliferation through the IL-6/STAT3 pathway.

Activation of interleukin-6/STAT3 in rat cholangiocyte proliferation induced by lipopolysaccharide.

BACKGROUND: Cholangiocytes are exposed to endotoxins (lipopolysaccharide, LPS) in a variety of biliary inflammations. It is known that LPS enhances the release of interleukin (IL)-6, a potent cholangiocyte mitogen. However, the role of LPS in cholangiocyte proliferation in vivo is unknown. Aims To investigate whether LPS stimulates cholangiocyte proliferation in vivo via the IL-6/STAT3 pathway. METHODS: Rats were randomized into four groups: the LPS group (injected intravenously with LPS 2.5 mg/kg), anti-IL-6 group (injected intravenously with anti-IL-6 0.5 mg/kg 1 h after LPS injection), RPM group (treated with RPM 0.4 mg/kg intraperitoneally 30 min before LPS injection), and control group. At 6, 12, 24, 48, and 72 h after LPS injection, LPS in plasma was detected by kinetic turbidimetric limulus test. IL-6 concentrations in liver homogenate and cholangiocyte proliferation were determined by ELISA or immunohistochemistry, respectively. Expression of IL-6 mRNA and phosphorylated-STAT3 (P-STAT3) protein in cholangiocytes was analyzed by real-time RT-PCR and western blotting. RESULTS: Cholangiocytes responded to LPS by a marked increase in cell proliferation, IL-6 secretion, and P-STAT3 expression. Anti-IL-6 neutralizing antibody inhibited LPS-induced proliferation of cholangiocytes and decreased levels of IL-6 and STAT3. Furthermore, after being treated with RPM, STAT3 activation was also depressed, which resulted a decreased proliferation of cholangiocytes. CONCLUSIONS: LPS promotes cholangiocyte proliferation through the IL-6/STAT3 pathway, while RPM shows a depressive effect in this pathway.

[Effects of LH analogs on the secretion of NGF in submaxillary gland cells of rats in vitro].

AIM: To investigate the effects of luteinizing hormone (LH) analogs on the secretion of nerve growth factor (NGF) in submandibular gland cells of rats in vitro. METHODS: The submandibular gland cells of rats were incubated in vitro and LH analogs at various concentration were added to the medium. The never growth factor (NGF) was detected by enzyme-link immunoassay (ELISA). RESULTS: When LH analogs were at the concentration of 10(-6), 10(-4), 10(-2) U/L respectively, the secretion of NGF was gradually increased. However, when LH analogs were at the concentration of 10(-2), 10(0), 10(2) U/L respectively, the secretion of NGF was gradually decreased. When LH analogs (10(-5) IU/mL) were incubated at different time, the secretion of NGF was different. NGF reached the peak value when it was incubated for 8 h and then decreased gradually. CONCLUSION: LH analogs may regulate the secretion of NGF in the submaxillary gland cells of rats.

Short-term anti-CD25 monoclonal antibody treatment and neogenetic CD4(+)CD25(high) regulatory T cells in kidney transplantation.

CD4(+)CD25(high) T cells named regulatory T (Treg) cells are generated and play a key role in the induction and maintenance of transplant tolerance in organ recipients. Interleukin-2 (IL-2) enhance the development of effector cells and is essential for generation of Treg cells. The effect of the anti-CD25 monoclonal antibody (anti-CD25mAb) induction therapy on the neogenetic CD4(+)CD25(high)Treg cells is important for therapeutic strategies in kidney transplant. To clarify the question, a prospective study was conducted in 21 living donor kidney transplant recipients who randomly divided into the anti-CD25mAb group (Daclizumab) with 11 patients and the control group with 10 patients. The frequency of CD4(+)CD25(high)Treg cells in total CD4(+) T cells was analyzed by flow cytometry and FoxP3 expression by RT-PCR in peripheral blood, and results were compared at day 0, 3, 13, 17, 27 posttransplantation. There was no significant difference in patient characteristics and allograft survival. The present study showed that in vivo antigen-specific Treg cells population were generated and expanded after transplant. Both groups showed a significant increase in the frequency of CD4(+)CD25(high)Treg cells and higher level of FoxP3 mRNA after transplantation while the serum creatinine declined. Compared with the control group, recipients with anti-CD25mAb injection had significantly lower percentage of CD4(+)CD25(high) in total CD4(+) cells (1.13%+/-0.13% vs 1.94%+/-0.22%, P=0.00; 3.75%+/-0.28% vs 7.11%+/-0.51%, P=0.00) on day 3, 17 after transplantation. While, the percentage was not significantly different on day 10, 27 (3.72%+/-0.19% vs 4.36%+/-0.28%, P=0.08; 7.84%+/-0.35% vs 8.56%+/-0.36%, P=0.16). However, there was not obvious difference in Foxp3 expression level associated with the source of the CD4(+)CD25(high)Treg cells at the different time point after transplant. Our data indicated that CD4(+)CD25(high)Treg cells were transiently affected by anti-CD25mAb, without depletion. In conclusion, the short-term treatment with anti-CD25mAb might not prevent the production, proliferation of neogenetic Treg cells in organ transplant.

Endothelial cell chimerism by fluorescence in situ hybridization in gender mismatched renal allograft biopsies.

BACKGROUND: The blood vessels of a transplanted organ are the interface between donor and recipient. The endothelium in the blood vessels is thought to be the major target for graft rejection. Endothelial cells of a transplanted organ can be of recipient origin after transplantation. In this study, we tested whether endothelial chimerism correlated with the graft rejection and cold ischemia. METHODS: We studied the biopsy samples from 34 renal transplants of female recipients who received the kidney from a male donor for the presence of endothelial cells of recipient origin. We examined the tissue sections of renal biopsy samples by fluorescence in situ hybridization (FISH) for the presence of endothelial cells containing two X chromosomes using a biotinylated Y chromosome probe and digoxigenin labelled X chromosome probe, and then analyzed the relationship between the endothelial cell chimerism and the rejection and cold ischemia. RESULTS: Endothelial chimerism was common and irrespective of rejections (P > 0.05). The cold ischemic time of chimerism group was longer than no chimerism group ((14.83 +/- 4.03) hours vs (11.27 +/- 3.87) hours, P < 0.05). CONCLUSIONS: There is no correlation between the percentage of recipient endothelial cells in vascular endothelial cells and the type of graft rejection. The endothelium damaged by ischemic injury might be repaired by the endothelial cells from the recipient.