Mechanism of Porphyra Yezoensis Polysaccharides in Inhibiting Hyperoxalate-Induced Renal Injury and Crystal Deposition.

Oxidative damage to the kidneys is a primary factor in the occurrence of kidney stones. This study explores the inhibitory effect of Porphyra yezoensis polysaccharides (PYP) on oxalate-induced renal injury by detecting levels of oxidative damage, expression of adhesion molecules, and damage to intracellular organelles and revealed the molecular mechanism by molecular biology methods. Additionally, we validated the role of PYP in vivo using a crystallization model of hyperoxalate-induced rats. PYP effectively scavenged the overproduction of reactive oxygen species (ROS) in HK-2 cells, inhibited the adhesion of calcium oxalate (CaOx) crystals on the cell surface, unblocked the cell cycle, restored the depolarization of the mitochondrial membrane potential, and inhibited cell death. PYP upregulated the expression of antioxidant proteins, including Nrf2, HO-1, SOD, and CAT, while decreasing the expression of Keap-1, thereby activating the Keap1/Nrf2 signaling pathway. PYP inhibited CaOx deposition in renal tubules in the rat crystallization model, significantly reduced high oxalate-induced renal injury, decreased the levels of the cell surface adhesion proteins, improved renal function in rats, and ultimately inhibited the formation of kidney stones. Therefore, PYP, which has crystallization inhibition and antioxidant properties, may be a therapeutic option for the treatment of kidney stones.

Porphyra yezoensis polysaccharide and potassium citrate synergistically inhibit calcium oxalate crystallization induced by renal epithelial cells and cytotoxicity of the formed crystals.

Mineralization crystallization is considered to be the initial stage of stone formation. However, the formation of crystals and subsequent cell damage have rarely been investigated. An oxidatively damaged cell model was established using oxalic acid to injure human proximal tubular epithelial cells (HK-2). Subsequently, CaOx crystallization was induced by adding 2.0 mmol/L sodium oxalate solution. We compared the synergistic effects of PYPs with molecular weights of 49.54 kDa (PYP1) and 4.02 kDa (PYP2) and K3Cit on the inhibition of CaOx crystallization and studied the nucleation, growth, and retention process of CaOx crystals on the cell surface and the subsequent damage of the formed crystals to the cells. Normal HK-2 cells mainly induced the formation of CaOx dihydrate (COD), whereas the damaged cells mainly induced the formation of CaOx monohydrate (COM) crystals. Under the protection of PYPs, the state of cells was improved, and the proportion of COD crystals in the formed crystals increased. Small-molecular-weight PYP2 exhibited better abilities of inhibiting CaOx crystallization and improving cell state compared with PYP1. Under the synergistic effects of PYPs and K3Cit, the number of formed crystals was obviously reduced, and the size was obviously decreased. PYPs can repair damaged cells and inhibit the conversion of COD phase to COM phase. K3Cit can obviously inhibit the nucleation of CaOx crystal and reduce the amount of crystal formation. The repair of damaged cells by PYPs and the synergistic inhibition of CaOx crystallization by PYPs and K3Cit reduce cell damage and crystal formation on the cell surface. By simultaneously repairing damaged cells and inhibiting crystallization, this strategy is expected to exert a desirable effect in preventing the formation and recurrence of stones.

[Platelet-derived growth factor-BB induces phenotypic transformation of corpus cavernosum smooth muscle cells in SD rats].

OBJECTIVE: To evaluate the effect of the platelet-derived growth factor-BB (PDGF-BB) on the phenotypic transformation of corpus cavernosum smooth muscle cells (CCSMC) in SD rats. METHODS: CCSMCs were primarily cultured in the modified tissue sticking medium and subjected to immunofluorescence assay. The cells were divided into a blank control and four PDGF-BB groups, the latter exposed to 5, 10, 20, and 40 ng/ml of PDGF-BB, respectively, for 24 hours, and the cells in the 20 ng/ml PDGF-BB group treated for 24, 48, and 72 hours. The the relative expressions of α-SMA, SMMHC, calponin, and OPN mRNA were determined by real-time fluorescence quantitative RT-PCR (qRT-PCR). RESULTS: The α-SMA positive rate of the CCSMCs was over 95%. Compared with the blank control group, the expression levels of α-SMA, SMMHC, and calponin mRNA were significantly decreased (P < 0.05) while that of OPN mRNA remarkably increased (P < 0.05) in the PDGF-BB groups. The 20 ng/ml PDGF-BB group also showed significantly downregulated expressions of α-SMA, SMMHC, and calponin mRNA (P < 0.05) and upregulated expression of OPN mRNA (P < 0.05) at 24, 48, and 72 hours. CONCLUSION: PDGF-BB can induce the transformation of the phenotype of CCSMCs in SD rats from the contractile to the synthetic type.

miR-195 Inhibits Tumor Progression by Targeting RPS6KB1 in Human Prostate Cancer.

PURPOSE: To investigate the involvement of hsa-miRNA-195-5p (miR-195) in progression and prognosis of human prostate cancer. EXPERIMENTAL DESIGN: qRT-PCR was performed to detect miR-195 expression in both prostate cancer cell lines and clinical tissue samples. Its clinical significance was statistically analyzed. The roles of miR-195 and its candidate target gene, ribosomal protein S6 kinase, 70 kDa, polypeptide 1 (RPS6KB1) in prostate cancer progression were confirmed on the basis of both in vitro and in vivo systems. RESULTS: miR-195 downregulation in prostate cancer tissues was significantly associated with high Gleason score (P = 0.001), positive metastasis failure (P < 0.001), and biochemical recurrence (BCR, P < 0.001). Survival analysis identified miR-195 as an independent prognostic factor for BCR-free survival of prostate cancer patients (P = 0.022). Then, we confirmed the tumor suppressive role of miR-195 through prostate cancer cell invasion, migration, and apoptosis assays in vitro, along with tumor xenograft growth, angiogenesis, and invasion in vivo according to both gain-of-function and loss-of-function experiments. In addition, RPS6KB1 was identified as a novel direct target of miR-195 through proteomic expression profiling combined with bioinformatic target prediction and luciferase reporter assay. Moreover, the reexpression and knockdown of RPS6KB1 could respectively rescue and imitate the effects induced by miR-195. Importantly, RPS6KB1 expression was closely correlated with aggressive progression and poor prognosis in prostate cancer patients as opposed to miR-195. Furthermore, we identified MMP-9, VEGF, BAD, and E-cadherin as the downstream effectors of miR-195-RPS6KB1 axis. CONCLUSION: The newly identified miR-195-RPS6KB1 axis partially illustrates the molecular mechanism of prostate cancer progression and represents a novel potential therapeutic target for prostate cancer treatment.

Osteopontin-induced brown adipogenesis from white preadipocytes through a PI3K-AKT dependent signaling.

Recent studies have shown that OPN (osteopontin) plays critical roles in cell survival, differentiation, bio-mineralization, cancer and cardiovascular remodeling. However, its roles in the differentiation of brown adipocytes and the underlying mechanisms remain unclear. Therefore, the aim of this study was to investigate the roles of OPN in the brown adipogenesis and the underlying mechanisms. It was shown that the OPN successfully induced the differentiation of 3T3-L1 white preadipocytes into the PRDM16(+) (PRD1-BF1-RIZ1 homologous domain containing 16) and UCP-1(+) (uncoupling protein-1) brown adipocytes in a concentration and time-dependent manner. Also, activation of PI3K (phosphatidylinositol 3-kinase)-AKT pathway was required for the OPN-induced brown adipogenesis. The findings suggest OPN plays an important role in promoting the differentiation of the brown adipocytes and might provide a potential novel therapeutic approach for the treatment of obesity and related disorders.

Types of Renal Calculi and Management Regimen for Chinese Minimally Invasive Percutaneous Nephrolithotomy.

Strict selection of patients for minimally invasive percutaneous nephrolithotomy could effectively improve the success rate of surgery. This study aimed to understand the required skills and the efficacy of mini-PCNL in the treatment of five types of upper ureteral calculi. Data collected after X-ray analysis and B mode ultrasound from 633 patients with upper ureteral and renal pelvis calculi who underwent B ultrasound-guided lithotomy was reviewed, including the following: type I, upper ureteral or renal pelvis calculi with moderate hydronephrosis (154 cases); type II, upper ureteral or renal pelvis calculi with severe hydronephrosis (157 cases); type III, upper ureteral or renal pelvis calculi without hydronephrosis (61 cases); type IV, renal pelvis calculi, one or two renal calyx calculi (206 cases); and type V, renal staghorn calculi (55 cases). Operations on 611 cases were successful. The treatment method for five patients was converted to open surgery. Twelve cases were treated by indwelling double-J tube retro-catheterization and extracorporeal shock wave lithotripsy. Five patients gave up the treatment. The rate of calculus clearance was 82.3 %, and the rate of residual calculus was 17.6 %. Selective renal artery embolization was performed in nine cases. Hydropneumothorax occurred in nine cases. No intestinal fistula occurred, and no patient had to undergo nephrectomy. The difficulty and the curative effect of the operation were different because the types of calculi varied. Selection of the procedure based on the different types of calculi could effectively improve the success rate of the procedure, reduce complications, and shorten the learning curve.

Erratum to: Types of Renal Calculi and Management Regimen for Chinese Minimally Invasive Percutaneous Nephrolithotomy.

[This corrects the article DOI: 10.1007/s12262-014-1043-4.].

A role for diallyl trisulfide in mitochondrial antioxidative stress contributes to its protective effects against vascular endothelial impairment.

Persistent hyperglycemia increases a systemic oxidative stress, causing the onset of vascular endothelial dysfunction and atherosclerosis. Diallyl trisulfide (DAT), a natural organosulfur compound in garlic, has been reported to have actions of dilating blood vessels and antibacteria, etc. In this study, models of obese diabetic rat in vivo and high glucose concentration (HG)-induced endothelial cell injury in vitro were used to investigate the protective effects of DAT on vascular endothelial injury and its underlying mechanisms. In the in vivo model, the obese diabetic rats were injected venously with DAT (5.0 mg kg(-1)d(-1)) and Vitamin E (1.0 mg kg(-1)d(-1)) respectively, once daily for 7 consecutive days. In the in vitro model, HG-injured HUVEC were treated with or without DAT (25 µmol L(-1), 50 µmol L(-1), 100 µmol L(-1)) or Vitamin E (25 µmol L(-1)) respectively for 24h. The extents of vascular endothelial injury and protective effects of DAT were evaluated. The results both in vivo and in vitro displayed that DAT-treatment significantly attenuated the endothelial cell impairments. Besides, DAT-treatment markedly decreased the levels of malondialdehyde (MDA) and reactive oxygen species, whereas elevated the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in mitochondrium. Moreover, DAT-treatment considerably improved mitochondrial respiration function. Taken together, our results suggest that DAT protects vascular endothelium from HG or hyperglycemia induced-injury by reducing mitochondrial oxidative stress. The findings provide a novel insight for DAT to potentially treat the oxidative stress diseases, i.e., atherosclerosis, diabetes, and neurodegenerative diseases.

Theoretical Studies on Pyrazolo[3,4-d]pyrimidine Derivatives as Potent Dual c-Src/Abl Inhibitors Using 3D-QSAR and Docking Approaches.

In recent years, the development of dual or multi-targeted inhibitors has captured extensive attention of research for treating of malignancies. In this paper, three-dimensional quantitative structure-activity relationship and docking studies were performed on 87 pyrazolo[3,4-d]pyrimidines as dual Src/Abl inhibitors. The appropriate binding orientations and conformations of these compounds interacting with both Src and Abl kinases were revealed by docking studies, and the established optimum CoMFA models yielded q(2) =0.856, R(2) =0.966 for Src and q(2) =0.869, R(2) =0.974 for Abl, and the best CoMSIA models gave q(2) =0.877, R(2) =0.979 for Src and q(2) =0.885, R(2) =0.982 for Abl. Systemic external validations further confirm the satisfactory predictive power of these models, producing R(2) pred values of 0.872 and 0.865 for Src, 0.876 and 0.867 for Abl, r(2) m values of 0.832 and 0.928 for Src, 0.838 and 0.904 for Abl, respectively. In addition, through a comparison between 3D-QSAR contour maps and docking results, it is revealed that the hydrophobic and electrostatic interactions of compounds play significant roles for the inhibitory activity against both Src and Abl kinases. Some structural factors influencing the activities of these compounds were discussed in detail. The key amino acids impacting the receptor-ligand interactions have been identified. These theoretical results can offer useful references for designing novel potential dual Src/Abl inhibitors.

Extracellular matrix metalloproteinase inducer: a novel poor prognostic marker for human seminomas.

OBJECTIVE: Extracellular matrix metalloproteinase inducer (EMMPRIN) is a glycosylated member of the immunoglobulin superfamily whose function in human seminomas is unknown. We have recently determined that EMMPRIN possesses the ability to stimulate fibroblast and endothelial cell matrix metalloproteinase production, and that its expression was frequently up-regulated in several tumours of the urinary system. Thus, EMMPRIN expression might be associated with the progression of human seminomas. The aim of this study was to investigate whether the presence of EMMPRIN in seminoma tissues might help to predict the patients' prognosis. METHODS: Paraffin-embedded tissues from 65 patients with seminomas and 20 normal testes were processed for immunohistochemical staining using a mouse monoclonal antibody generated against human EMMPRIN, as primary antibody, and a biotinylated goat-anti-mouse IgG, as secondary antibody. In addition, the correlation of EMMPRIN expression with clinicopathologic characteristics and patients' prognosis was also analysed. RESULTS: EMMPRIN was detected in cancerous tissues of 53 patients with seminoma, but not normal testes. Thirty- five patients showed weakly to moderately positive and 18 patients intensely positive expression. Moreover, positive EMMPRIN staining correlated significantly with various clinicopathological factors (increased TNM stage and higher histological differentiation type) as well as decreased tumour-specific survival (log-rank, p=0.02). In particular, EMMPRIN expression was an independent prognosticator as shown by Cox regression analysis (p<0.001). CONCLUSION: EMMPRIN expression in a primary tumour predicts an unfavourable prognosis in human seminoma, suggesting its crucial role in the progression of this tumour.

Theoretical studies of QSAR and molecular design on a novel series of ethynyl-3-quinolinecarbonitriles as SRC inhibitors.

A theoretical study on the two-dimensional, three-dimensional quantitative structure-activity relationships and docking analysis of a novel series of ethynyl-3-quinolinecarbonitriles acting as Src inhibitors has been carried out. To correlate the c-Src kinase-inhibition activity of these compounds with the two-dimensional and three-dimensional structural properties for 39 known compounds, some excellent quantitative structure-activity relationships models with satisfying internal and external predictive abilities were established. A combined method of the density functional theory, molecular mechanics and statistics as well as the comparative molecular field analysis was applied to develop two-dimensional- and three-dimensional-quantitative structure-activity relationship models. The leave-one-out cross-validation q² values of two-dimensional-quantitative structure-activity relationship and comparative molecular field analysis models are 0.834 and 0.812, respectively. The predictive abilities of these models were further validated by the test set including 10 compounds, and the predicted IC50 values were in a good agreement with the experimental ones. The appropriate binding orientations and conformations of these compounds interacting with c-Src kinase were also revealed by the docking study. Based on two-dimensional- and three-dimensional-quantitative structure-activity relationship results along with docking analysis, some important factors responsible for inhibitory activity of this series of compounds were discussed in detail. These factors can be summarized as follows: selecting certain large-size substituent R2, increasing the negative charge of the first atom of substituent R1 and the net charge of the C15 atom on ring-C will enhance the activity. Meanwhile, the interaction information between protein and ligand was also revealed in detail. These results help to understand the action mechanism and designing novel potential Src inhibitors. Based on the established models and some designing considerations, three new compounds with rather high predicted Src-inhibitory activity have been theoretically designed and presented to experimenters for reference.

Expression of CD147 is associated with prostate cancer progression.

Novel molecular markers that are associated with prostate cancer (PCa) progression will provide valuable information in the diagnosis and treatment of the disease. Extracellular matrix metalloproteinase inducer (CD147) has been demonstrated to be involved in tumor invasion, metastasis, growth and survival. In our study, we examined whether the expression of CD147 can be used as a prognostic marker for predicting PCa progression. Tissue samples from 240 patients who received radical prostatectomy for PCa were obtained. CD147 expression in these samples was evaluated using immunohistochemical staining with a monoclonal antibody specifically against CD147. Increased expression of CD147 was correlated with higher Gleason scores (GS), positive surgical margin, prostate-specific antigen (PSA) failure, metastasis and reduced overall survival. Both univariate Cox regression analysis and multivariate analysis including competing biological variables demonstrated that increased CD147 expression was associated with increased risk for reduced PSA failure-free, metastasis-free and overall survival. Kaplan-Meier survival curves showed that the CD147 overexpression was a significant predictor for the PSA failure-free, metastasis-free and the overall survival in both pT2 and pT3 PCa patients. More significantly, higher expression of CD147 can serve as an independent prognostic predictor for PSA failure-free survival in PCa patients when they are stratified by GS. Our study results demonstrate the involvement of CD147 in PCa progression and suggest its potential role as an independent predictor of biochemical recurrence, development of metastasis and reduced overall survival in PCa.

Expression of hedgehog pathway components is associated with bladder cancer progression and clinical outcome.

Hedgehog (Hh) pathway has been implicated in the tumorigenesis of a large number of human tumors. But its effects on the progression and prognosis of bladder cancer remain poorly understood. The aim of this study was to investigate expression patterns of Hh pathway components in bladder cancer and to elucidate their prognostic values in this tumor. The expression of sonic hedgehog (Shh), its receptor Patched (Ptch1), and downstream transcription factor Gli1 in 118 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between the expression of these three proteins and clinicopathologic features and prognosis. Immunohistochemical staining results showed the localizations of Shh and Ptch1 proteins to be mainly located in the cytoplasm of bladder cancer cells, whereas Gli1 was mainly localized in the nuclear of tumor cells. Additionally, positive expression of Shh, Ptch1 and Gli1 proteins was correlated with pathological stage (P = 0.006, 0.006 and 0.008, respectively), venous invasion (P = 0.01, 0.01 and 0.012, respectively) and lymph node metastasis (P = 0.009, 0.01 and 0.013, respectively), but not with other factors including age, gender, tumor grade and recurrence of superficial cancer. Moreover, patients with positive expression of Shh, Ptch1 and Gli1 proteins respectively showed poorer disease-free (P = 0.002, 0.002 and 0.001, respectively) and overall survival (all P < 0.001) than those with negative expression of these three proteins. Univariate and multivariate analysis of prognostic factors in bladder cancer patients indicated that the expression patterns of Shh, Ptch1 and Gli1 proteins were independent unfavorable prognostic factors (all P < 0.001). This is the first report describing about the correlation between Hh pathway and the prognosis of bladder cancer. Expression of Shh, Ptch1 and Gli1 proteins was greater in bladder cancers than in the adjacent normal tissues. The examination of their expression is potentially valuable in prognostic evaluation of bladder cancer.

Classical and alternative nuclear factor-κB pathways: a comparison among normal prostate, benign prostate hyperplasia and prostate cancer.

Nuclear factor-κB (NF-κB) is controlled by the classical and alternative NF-κB pathways, the role of which in prostate cancer (PCa) is not clearly defined. To provide this missing translational link, we compared the classical and alternative NF-κB pathways in normal prostate, benign prostate hyperplasia (BPH) and PCa. Prostate specimens were divided into three groups: group A, PCa (n = 68); group B, BPH (n = 60); and group C, normal prostates (n = 15). The gene expression levels of NF-κB1 and NF-κB2 were determined by real-time quantitative RT-PCR. Additionally, we analyzed the expression and sub-cellular localization of phosphorylated P50 (p-P50) and phosphorylated P52 (p-P52) proteins by immunohistochemical staining. Furthermore, associations were made between NF-κB pathway proteins and patients' prognosis. Compared with BPH and normal prostate tissues, the expression of NF-κB1 gene was differentially down-regulated by >1.5-fold, whereas NF-κB2 gene was differentially up-regulated by >2-fold in PCa tissues. The proportion of p-P50 positive patients in group A (26.5%) was significantly lower than in group B (88.3%, p = 0.005) and C (100%, p = 0.002). The proportion of p-P52 positive patients in group A (42.6%) was significantly higher than in group B (11.7%, p = 0.009) and C (6.7%, p = 0.008). Comparison of the survival curves in group A according to p-P52 expression showed a significant difference between positive and negative patients. The p-P52 positive patients showed worse prognosis (p = 0.019). Our findings suggest for the first time that the classical and alternative NF-κB pathways have an important role in PCa. p-P52 might be a predictor of poor prognosis for PCa.

Extracellular matrix metalloproteinase inducer expression has an impact on survival in human bladder cancer.

AIM: Extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to promote tumor invasion and metastasis via stimulating matrix metalloproteinase synthesis in neighboring fibroblasts, to enhance angiogenesis via vascular endothelial growth factor, to induce chemoresistant tumor cells via the production of hyaluronan, and to confer resistance of cancer cells to anoikis through inhibition of Bim. The purpose of this study was to investigate the expression of EMMPRIN in human primary bladder cancer and to evaluate its prognostic value. METHODS: EMMPRIN expression patterns were detected by immunohistochemistry. In order to determine its prognostic value, overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. RESULTS: Of the 101 cases with bladder cancers, 68 (67.3%) cases were positive for EMMPRIN expression. When categorized into negative vs. positive expression, EMMPRIN was associated with the stage (p=0.006), the grade (p=0.002), carcinoma in situ (p=0.01), the recurrence (p=0.009), the progression (p=0.009), and the death (p=0.01) of patients with bladder cancer. Moreover, positive EMMPRIN expression clearly predicted poorer PFS (p=0.008) and OS (p=0.006). In the multivariate analysis, positive EMMPRIN expression was an independent prognostic factor for PFS (p=0.03) and OS (p=0.03). CONCLUSION: EMMPRIN expression was greater in bladder cancers than in the adjacent normal tissues and may be a useful prognostic marker for patients with bladder cancer.

CK20 and Ki-67 as significant prognostic factors in human bladder carcinoma.

Aberrant expression of CK20 and Ki-67 has been documented in many kinds of primary tumors and has proved useful as an ancillary diagnostic aid for those tumors. The aim of this study was to analyze the expression patterns of CK20 and Ki-67 in human bladder carcinomas (BCa) and to evaluate their clinical significance in the progression of BCa. CK20 and Ki-67 expression in BCa and normal bladder tissues were detected by immunohistochemical staining. The Spearman correlation was calculated between the expression of CK20 and Ki-67 in BCa tissues. The correlation of CK20 and Ki-67 expression with the clinicopathological characteristics and the prognosis of BCa were subsequently assessed. CK20 expression was positively expressed in 103/154 (66.9%) of BCa and 2/30 (6.67%) of normal bladder tissues, respectively. The positive expression rate of Ki-67 in BCa tissues was also significantly higher than those in normal bladder tissues (81.8 vs. 10%, p < 0.01). The Spearman analysis indicated that the expression level of CK20 has a significant positive correlation with that of Ki-67 (rs = 0.86, p = 0.02). Pathologic findings demonstrated that the intensity of CK20 and Ki-67 staining in cancerous tissues was associated significantly with tumor grades (p = 0.03, p < 0.01), distant metastasis (both p < 0.01) and TNM grades (p = 0.01, p = 0.03) of BCa. The progression-free survival of the patients with CK20 (+)/Ki-67 (+) expression was poorest (p < 0.01). The results suggest that the expression of CK20 and Ki-67 may be an important feature of BCa, and the detection of their co-expression may benefit the prediction of BCa prognosis.

Expression and clinical significance of CD147 in genitourinary carcinomas.

BACKGROUND: CD147/extracellular matrix metalloproteinase inducer (EMMPRIN) expressed by tumor cells stimulates peri-tumorous fibroblasts to produce matrix metalloproteinases (MMPs), thus contributing to tumor invasion and metastasis. To assess its suitability as a potential therapeutic target, as well as its association with the clinicopathologic features and the prognosis of patients, the expression of CD147/EMMPRIN in neoplastic tissues of the genitourinary system were analyzed. METHODS: CD147/EMMPRIN expression in 52 patients with renal carcinoma, 58 patients with bladder carcinoma, 101 patients with prostate carcinoma, 17 patients of penis carcinoma, and 17 patients of testis carcinoma were examined by immunostaining on paraffin-embedded tumor specimens using monoclonal antibodies. Then, the association of its expression with clinicopathologic characteristics to the patients' prognosis was analyzed. The RNA interference approach was used to silence CD147/EMMPRIN expression in the human prostate carcinoma cell line LNCAP and human bladder carcinoma cell line J82. The in vitro proliferative ability of CD147/EMMPRIN-deficient cells was determined by a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay. RESULTS: CD147/EMMPRIN was expressed in neoplastic tissues, but not in normal tissues. Positive expression was shown in 42 of 52 (80.77%) of the patients with renal carcinoma, 41 of 58 (70.69%) of the patients with bladder carcinoma, 67 of 101 (66.34%) of the patients with prostate carcinoma, 16 of 17 (94.12%) of the patients with penis carcinoma and testis carcinoma. Positive CD147/EMMPRIN staining was significantly associated with TNM stages and histological subtypes of patients with various urinary carcinomas (P < 0.05). In all five groups, for different expression levels of CD147/EMMPRIN, the patients with a highly positive expression of CD147/EMMPRIN had the poorest prognosis. The siRNA-treated cells exhibited significantly decreased growth ability compared with control cells in vitro. CONCLUSION: These results may assist in defining the suitability of CD147/EMMPRIN as a therapeutic target and as a method for predicting a poor outcome in patients with various urinary carcinomas.

[Treatment of urinary tract calculi in preschool children with endoscopy].

OBJECTIVES: To investigate the safety and feasibility of endoscopy in treating urinary tract calculi in preschool children. METHODS: From August 2004 to August 2008, 28 preschool children with urinary tract calculi were treated by endoscopy, 11 cases received ureterolithotripsy (URL) and 17 cases received minimally invasive percutaneous nephrolithotomy (MPCNL). RESULTS: Of 11 cases with ureteric calculi, 5 cases were rendered stone free in the first session, the other 6 cases received passive dilation by indwelling of ureteric stents for 1 to 3 weeks and underwent successful ureteroscopy with a 8/9.8 Fr rigid ureteroscope. Seventeen cases with renal calculi received MPCNL and were rendered stone free. CONCLUSION: Our study shows that endoscopy in treating urinary tract calculi is safe and feasible in preschool children.

CD147 and VEGF expression in advanced renal cell carcinoma and their prognostic value.

AIM: To investigate the clinicopathologic characteristics of extracellular matrix (ECM) metalloproteinase inducer (CD147) and vascular endothelial growth factor (VEGF) expression in advanced renal cell carcinoma (RCC), and to evaluate the clinical significance of these two markers in the prognosis of advanced RCC. METHODS: CD147 and VEGF expression in paraffin-embedded specimens gathered from 53 patients with advanced RCC and 12 healthy controls were detected by the method of immunohistochemistry. The Spearman correlation was calculated between the expression levels of CD147 and VEGF in advanced RCC tissues. The association of CD147 and VEGF expression with the clinicopathologic features and prognosis of advanced RCC was subsequently assessed. RESULTS: CD147 and VEGF were positively expressed in 47/53 (88.7%) and 45/53 (84.9%) of patients with advanced RCC, respectively. Positive expression of CD147 (p= 0.02) and VEGF (p< 0.01) was significantly correlated with TNM stage of advanced RCC. A significant correlation was found between the expression of CD147 and VEGF in advanced RCC (r= 0.629, p= 0.04). Additionally, tumor CD147 and tumor VEGF expressions were significantly associated with the prognosis of advanced RCC patients. The survival rate of the patients with CD147-/VEGF- expression was the lowest (p< 0.01), and conjoined expressions of CD147-/VEGF- and CD147+/VEGF+ were independent prognostic indicators of advanced RCC (both p< 0.01). CONCLUSION: The expression of CD147 or VEGF may be an important feature of advanced RCC. A combined detection of CD147/VEGF coexpression may benefit us in the prediction of the prognosis of advanced RCC.

Pathogen incidence and antibiotic resistance patterns of catheter-associated urinary tract infection in children.

The aim of this study was to characterize the pathogens and their antibiotic susceptibilities in children with catheter-associated urinary tract infection (CAUTI) in order to optimize empirical antibiotic therapy and prophylaxis. from 2001 to 2006, 895 children with an indwelling catheter from 3 hospitals in China were included in this study, of whom 335 (37.4%) had CAUTI. Antimicrobial susceptibility testing of 450 bacterial isolates was performed using the ClSi broth and Kirby-bauer agar dilution methods. Escherichia coli was the most frequently isolated pathogen, followed by Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus spp. E. coli had higher susceptibility to ceftazidime (87.4%), cefuroxime (85.1%) and cefatrizine (76.6%) than to sulfamethoxazole (SMZ) (8.0%), amoxicillin (21.7%), ampicillin (17.1%) and cefazolin (37.7%). Isolates of Klebsiella pneumoniae and Proteus species had similar patterns as E. coli. S. aureus had lower susceptibility to SmZ (6.8%), ampicillin (8.2%), and amoxicillin (24.7%); the trend of S. epidermidis was similar. This study demonstrates that the Gram-negative species are the predominating uropathogens of CAUti in children. it is important to know the bacterial spectrum and the susceptibility patterns to various classes of antibiotic agents to improve empiric antibiotic therapy of children with CAUTI in China.