Causal effects of inflammatory bowel diseases on the risk of kidney stone disease: a two-sample bidirectional mendelian randomization.

BACKGROUND: Existing epidemiological observational studies have suggested interesting but inconsistent clinical correlations between inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), and kidney stone disease (KSD). Herein, we implemented a two-sample bidirectional Mendelian randomization (MR) to investigate the causal relationship between IBD and KSD. METHODS: Data on IBD and KSD were obtained from Genome-Wide Association Studies (GWAS) summary statistics and the FinnGen consortium, respectively. Strict selection steps were used to screen for eligible instrumental SNPs. We applied inverse variance weighting (IVW) with the fix-effects model as the major method. Several sensitivity analyses were used to evaluate pleiotropy and heterogeneity. Causal relationships between IBD and KSD were explored in two opposite directions. Furthermore, we carried out multivariable MR (MVMR) to obtain the direct causal effects of IBD on KSD. RESULTS: Our results demonstrated that CD could increase the risk of KSD (IVW: OR = 1.06, 95% CI = 1.03-1.10, p < 0.001). Similar results were found in the validation group (IVW: OR = 1.05, 95% CI = 1.01-1.08, p = 0.013) and in the MVMR analysis. Meanwhile, no evidence of a causal association between UC and KSD was identified. The reverse MR analysis detected no causal association. CONCLUSIONS: This MR study verified that CD plays a critical role in developing kidney stones and that the effect of UC on KSD needs to be further explored.

Chronic Obstructive Pulmonary Disease Mortality in Bladder Cancer Patients: A SEER-Based Competing Risk Analysis.

PURPOSE: This study was designed to evaluate risk of mortality from chronic obstructive pulmonary disease (COPD) in patients with bladder cancer (BC). METHODS AND MATERIALS: Data on patients diagnosed with BC by pathology between 2000 and 2016 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Based on reference data from the general population, the standardized mortality rate (SMR) is calculated. Nelson-Aalen cumulative hazard curves were used for assessment of the risk of COPD mortality in BC patients. Multivariable competing risk models were conducted. The proportional hazards assumption was tested using Schoenfeld residuals, which were scaled and plotted over time for each risk factor. RESULTS: A total of 237,563 BC patients were identified for further analysis from the SEER database, 5,198 of these patients experienced COPD mortality; the overall SMR for COPD mortality in BC patients was 1.58 (95% CI: 1.54-1.63). Age, race, year of diagnosis, histologic type, summary stage, surgery, marital status, college education level, and median household income independently predicted COPD mortality in BC patients. CONCLUSIONS: In comparison to the general population, the risk of COPD mortality is significantly higher in patients with BC. Pre-identification of high-risk groups and respiratory care provisions are important measures to effectively improve survival in this group of patients.

Therapeutic responses to chemotherapy or immunotherapy by molecular subtype in bladder cancer patients: A meta-analysis and systematic review.

To systematically evaluate the differences in therapeutic response to chemotherapy or immunotherapy between different molecular subtypes of bladder cancer (BC). A comprehensive literature search was performed up to December 2021. Consensus clusters 1 (CC1), CC2 and CC3 molecular subtypes were used to perform meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the therapeutic response by fix-effect modeling. Eight studies involving 1,463 patients were included. For immunotherapy, CC3 showed the highest response rate (CC1 vs. CC3: OR=0.52, 95% CI=0.34-0.78, p=0.002; CC2 vs. CC3: OR=0.42, 95% CI=0.28-0.62, p<0.001), which was mainly reflected in the highest response rate to atezolizumab (CC1 vs. CC3: OR=0.47, 95% CI=0.29-0.75, p=0.002; CC2 vs. CC3: OR=0.38, 95% CI=0.24-0.59, p<0.001). For chemotherapy, CC3 had the lowest response rate to the overall chemotherapy (CC1 vs. CC3: OR=2.05, 95% CI=1.23-3.41, p=0.006; CC2 vs. CC3: OR=2.48, 95% CI=1.50-4.10, p<0.001). Compared with CC2, CC3 responded poorly to both neo-adjuvant chemotherapy (NAC) (OR=1.93, 95% CI=1.09-3.41, p=0.020) and chemoradiation therapy (CRT) (OR=6.07, 95% CI=1.87-19.71, p<0.001). Compared with CC1, CC3 only showed a poorer response to CRT (OR=4.53, 95% CI=1.26-16.27, p=0.020), and no difference in NAC. Our study suggested that molecular classifications are important predictors of cancer treatment outcomes of BC patients and could identify subgroup patients who are most likely to benefit from specific cancer treatments.

High risk of non-cancer mortality in bladder cancer patients: evidence from SEER-Medicaid.

PURPOSE: The objective of this study was to investigate non-cancer causes of death and associated risk factors after bladder cancer (BC) diagnosis. METHODS: Eligible BC patients were obtained from the SEER database. SEER*Stat software 8.3.9.2 was used to calculate the standardized mortality ratios (SMRs). The proportions of different non-cancer cause of death were calculated and analyzed in different follow-up periods. Multivariate competing risk model was used to analyze the risk factors for death of BC and non-cancer diseases. RESULTS: In total, 240,954 BC patients were included and 106,092 patients experienced death, with 37,205 (35.07%), 13,208 (12.45%) and 55,679 (52.48%) patients experienced BC, other cancer and non-cancer disease-related deaths, respectively. Overall SMR for BC patients who died from non-cancer diseases was 2.42 (95% CI [2.40-2.44]). Cardiovascular diseases were the most common non-cancer cause of death, followed by respiratory diseases, diabetes mellitus, and infectious diseases. Multivariate competing risk analysis identified the following high-risk factors for non-cancer mortality: age > 60 years, male, whites, in situ stage, pathological type of transitional cell carcinoma, not receiving treatment (including surgery, chemotherapy, or radiation), and widowed. CONCLUSIONS: Cardiovascular diseases are the leading non-cancer cause of death in BC patients, followed by respiratory disease, diabetes mellitus and infectious diseases. Physicians should pay attention to the risk of death from these non-cancer diseases. Also, physicians should encourage patients to engage in more proactive self-surveillance and follow up.

Indocyanine Green-Loaded Nanobubbles Targeting Carbonic Anhydrase IX for Multimodal Imaging of Renal Cell Carcinoma.

Background and Purpose: The early diagnosis and differential diagnosis of renal cell carcinoma (RCC) has always been a clinical difficulty and a research focus. Carbonic anhydrase IX (CA IX) is highly expressed on the cell membrane of RCC but is not expressed in normal renal tissues. In this study, nanobubbles (NBs) targeting CA IX with ultrasound and photoacoustic multimodal imaging capabilities were prepared to explore a new method for the diagnosis and differential diagnosis of RCC. Methods: Indocyanine green (ICG)-loaded lipid NBs (ICG-NBs) were prepared by using the filming rehydration method, and anti-CA IX polypeptides (ACPs) were attached to their surfaces to prepare CA IX-targeted NBs (ACP/ICG-NBs). The particle size, zeta potential and ICG encapsulation efficiency of these nanobubbles were measured, and their specific targeting and binding abilities to RCC cells were determined. The in vitro and in vivo ultrasound, photoacoustic and fluorescence imaging characteristics of these nanobubbles were also assessed. Results: The particle size of the ACP/ICG-NBs was 475.9 nm in diameter, and their zeta potential was -2.65 mV. Laser confocal microscopy and flow cytometry both confirmed that ACP/ICG-NBs had specific binding activity and ideal affinity to CA IX-positive RCC cells (786-O) but not to CA IX-negative RCC cells (ACHN). The intensities of the in vitro ultrasound, photoacoustic and fluorescence imaging were positively correlated with the concentrations of ACP/ICG-NBs. In in vivo ultrasound and photoacoustic imaging experiments, ACP/ICG-NBs exhibited specific enhanced ultrasound and photoacoustic imaging effects in 786-O xenograft tumors. Conclusion: The ICG- and ACP-loaded targeted nanobubbles that we prepared had the capability of ultrasound, photoacoustic and fluorescence multimodal imaging and could specifically enhance the ultrasound and photoacoustic imaging of RCC xenograft tumors. This outcome has potential clinical application value for the diagnosis of RCC at the early stage and the differential diagnosis of benign and malignant kidney tumors.

NUF2 is correlated with a poor prognosis and immune infiltration in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies. Recently, immunotherapy has been considered a promising treatment for metastatic ccRCC. NUF2 is a crucial component of the Ndc80 complex. NUF2 can stabilize microtubule attachment and is closely related to cell apoptosis and proliferation. This research is dedicated to investigating the role of NUF2 in ccRCC and the possible mechanisms. METHODS: First, analysis of NUF2 mRNA expression levels in ccRCC and normal tissues by The Cancer Genome Atlas (TCGA) database and further verified by analysis of independent multiple microarray data sets in the Gene Expression Omnibus (GEO) database. Moreover, we evaluated and identified correlations between NUF2 expression, clinicopathologic variable, and overall survival (OS) in ccRCC by various methods. We investigated the relationship between NUF2 and tumor immune infiltration and the expression of corresponding immune cell markers via the Gene Expression Profiling Interactive Analysis (GEPIA) and Tumor Immune Estimation Resource (TIMER) databases. Then, we performed functional enrichment analysis of NUF2 co-expressed genes using R software and protein-protein interactions (PPIs) using the search tool used to retrieve interacting genes/proteins (STRING) databases. RESULTS: We discovered that NUF2 mRNA expression was upregulated in ccRCC tissues and was associated with sex, grade, pathological stage, lymph node metastasis, and worse prognosis. In addition, NUF2 was positively linked to tumor immune cells in ccRCC. Moreover, NUF2 was closely related to genetic markers of different immune cells. Finally, functional enrichment and protein-protein interaction (PPI) analysis suggested that NUF2 and its closely related genes may be involved in the regulation of the cell cycle and mitosis. Our results suggested that NUF2 is correlated with a poor prognosis and immune infiltration in ccRCC.

Incidence, Prognostic Factors, and Survival of Patients with Renal Cancer: A Population-Based Study.

BACKGROUND: The main objective of this article is to understand trends in the incidence of renal cancer and to construct a nomogram to predict the prognosis of patients with renal cancer by analyzing clinical parameters. METHODS: We extracted data from the Surveillance, Epidemiology and End Results (SEER) database for patients with renal cancer from 2010 to 2015. The incidence rate was calculated to understand the trend of renal cancer in recent years, and the Kaplan-Meier method was used to analyze the relationship between patients' clinical variables and overall survival. Nomogram and calibration curves were constructed based on factors predicted by multivariate Cox regression. RESULTS: Data from 68,496 eligible renal cancer patients were included in the study. The incidence of renal cancer was higher in men than women and tended to stabilize over time. We further found that age, gender, marital status, AJCC stage, histological type, metastatic disease, and surgery were independent parameters for prognosis in renal cancer patients. Finally, a nomogram was constructed based on the above parameters, and its validity was verified with the agreement index and calibration curve. CONCLUSION: Renal cancer incidence trend gradually stabilized. Seven independent parameters for renal cancer patients were obtained by analysis and utilized to construct a nomogram that could provide guidance for clinical practice.

A positive feedback loop between tryptophan hydroxylase 1 and ß-Catenin/ZBP-89 signaling promotes prostate cancer progression.

Alterations in tryptophan (Trp) metabolism facilitate the continuous modulation of tumor progression, including tumor growth, distant metastasis, and chemoresistance development. Although there is a high correlation between Trp metabolism and tumor progression, it is unknown whether and how Trp metabolism affects the development of prostate cancer. In this study, we reported that the overexpression of Trp hydroxylase 1 (TPH1) caused the upregulation of Trp hydroxylation and mediated the production of 5-hydroxytryptamine (5-HT), contributing to tumor growth and poor prognosis in patients with prostate cancer. An increase in 5-HT levels triggered the activation of the Axin 1/ß-catenin signaling pathway, thus enhancing cell proliferation and migration. Consequently, ß-catenin cooperated with the Krüppel-type zinc finger family transcription factor ZBP-89 to upregulate TPH1 expression, further promoting Trp hydroxylation and forming the TPH1/5-HT/ß-catenin/ZBP-89/THP1 positive feedback signaling loop. Interruption of the signaling loop by the THP1 inhibitor 4-chloro-dl-phenylalanine (PCPA) significantly improved anticancer effects and suppressed lung metastasis in prostate cancer-bearing mice. Our findings revealed a mechanism by which TPH1 promotes prostate cancer growth by inducing Trp hydroxylation and identified a novel THP1 target for an innovative prostate cancer therapeutic strategy.

Incidence, prognostic factors and survival in bladder cancer patients: a population-based study.

Background: The aim of this study was to investigate the incidence, epidemiologic characteristics, prognostic factors and survival of patients with bladder cancer. Methods: Bladder cancer patients diagnosed between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox proportional hazards regression analyses were used to identify the independent prognostic factors for overall survival. Kaplan-Meier survival analysis and nomogram analysis were constructed based on the identified independent prognostic factors. Results: A total of 95,329 eligible bladder cancer patients were included in this study. Eight independent risk factors, including age, histologic type, race, tumor, node and metastasis (TNM) stage, American Joint Committee on Cancer (AJCC) stage, surgery, tumor metastasis and summary stage, were recognized by using multivariate logistic regression models. By comprising these factors, a predictive nomogram was constructed to predict the 1-, 3-, and 5-year overall survival possibilities. The concordance index and calibration curve showed that the nomogram had robust and accurate performance. Conclusions: Bladder cancer is the most common cancer of the urinary system, but the overall incidence has been decreasing yearly since 1992. Our results demonstrate eight factors significantly associated with overall survival in bladder cancer patients. Based on these factors, we established and validated a nomogram, which has the potential to provide an individualized prediction of overall survival in patients with bladder cancer.

Cardiovascular Mortality Risk in Patients with Bladder Cancer: A Population-Based Study.

BACKGROUND: The purpose of this study was to evaluate the risk of cardiovascular mortality (CVM) among patients with bladder cancer (BC). METHODS AND MATERIALS: Data were collected from the Surveillance, Epidemiology, and End Results (SEER) database for patients who were diagnosed with BC by pathology between 2000 and 2016. The standardized mortality rate (SMR) was calculated based on reference data from the general population. Nelson-Aalen cumulative hazard curves were used to assess the risk of experiencing CVM in BC patients. Multivariate competing risk models were performed. RESULTS: In total, data from 237,563 BC patients were obtained from the SEER database for further analysis, of which 21,822 patients experienced CVM; the overall SMR for CVM in BC patients was 1.16 (95% CI: 1.14-1.17). Age, race, sex, year of diagnosis, histologic type, summary stage, surgery, marital status, and college education level were independent predictors of CVM in patients with BC. CONCLUSIONS: Patients with BC have a significantly increased risk of experiencing CVM compared to the general population. Pre-identification of high-risk groups and cardiovascular protection interventions are important measures to effectively improve survival in this group of patients.

A Novel Pyroptosis-Related Gene Signature for Predicting Prognosis in Kidney Renal Papillary Cell Carcinoma.

Pyroptosis is defined as an inflammatory form of programmed cell death. Increasing studies have demonstrated that pyroptosis is closely related to tumor development and antitumor process. However, the role of pyroptosis in kidney renal papillary cell carcinoma (KIRP) remains obscure. In this study, we analyzed the expression of 52 pyroptosis-related genes (PRGs) in KIRP, of which 20 differentially expressed PRGs were identified between tumor and normal tissues. Consensus clustering analysis based on these PRGs was used to divided patients into two clusters, from which a significant difference in survival was found (p = 0.0041). The prognostic risk model based on six PRGs (CASP8, CASP9, CHMP2A, GPX4, IL6, and IRF1) was built using univariate Cox regression and LASSO-Cox regression analysis, with good performance in predicting one-, three-, and five-year overall survival. Kaplan-Meier survival analysis showed that the high-risk group had a poor survival outcome (p < 0.001) and risk score was an independent prognostic factor (HR: 2.655, 95% CI 1.192-5.911, p = 0.016). Immune profiling revealed differences in immune cell infiltration between the two groups, and the infiltration of M2 macrophages was significantly upregulated in the tumor immune microenvironment, implying that tumor immunity participated in the KIRP progression. Finally, we identified two hub genes in tumor tissues (IL6 and CASP9), which were validated in vitro. In conclusion, we conducted a comprehensive analysis of PRGs in KIRP and tried to provide a pyroptosis-related signature for predicting the prognosis.

Effect of Brachytherapy vs. External Beam Radiotherapy on Sexual Function in Patients With Clinically Localized Prostate Cancer: A Meta-Analysis.

Purpose: The aim of this study was to compare the effect of brachytherapy (BT) versus external beam radiotherapy (EBRT) on sexual function in patients with localized prostate cancer (PCa). Methods: Data were retrieved from the PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang Database until March 4, 2021. Analysis was performed by using RevMan 5.4.1. The main clinical outcomes were the Prostate Cancer Symptom Indices (PCSI) scale and the Expanded Prostate Cancer Index Composite (EPIC) scale scores for sexual function. A meta-analysis was performed to calculate standardized mean differences (SMDs) and their 95% CI. This study has undergone PROSPERO registration (No. CDR42021245438). Results: Among the 962 studies retrieved, eight prospective cohort studies met the inclusion criteria, covering a total of 2,340 patients, including 1,138 treated with BT alone and 1,202 treated with EBRT alone. The results demonstrated that BT was to some extent advantageous over EBRT in overall sexual function scores in patients with localized PCa during the immediate post-treatment period (SMD = -0.09, 95% CI: -0.18 to -0.01, p = 0.03), but this difference was not detectable at 3 months (SMD = -0.07, 95% CI: -0.18-0.05, and p = 0.25), 12 months (SMD = -0.01, 95% CI: -0.21-0.20, and p = 0.96), and 24 months (SMD = -0.09, 95% CI: -0.20-0.01, and p = 0.09) after treatment. Conclusion: Our analysis showed that BT showed a short-term advantage over EBRT in terms of sexual function in patients with localized PCa, but this difference diminished over time, though the conclusion needs to be further verified by a longer-term follow-up study.

Squamous cell carcinoma of the renal parenchyma presenting as hydronephrosis: a case report and review of the recent literature.

BACKGROUND: Primary squamous cell carcinoma of the renal parenchyma is extremely rare, only 5 cases were reported. CASE PRESENTATION: We probably report the fifth case of primary Squamous cell carcinoma (SCC) of the renal parenchyma in a 61-year-old female presenting with intermittent distending pain for 2 months. Contrast-enhanced computed tomography (CECT) revealed hydronephrosis of the right kidney, but a tumor cannot be excluded completely. Finally, nephrectomy was performed, and histological analysis determined that the diagnosis was kidney parenchyma squamous cell carcinoma involving perinephric adipose tissue. CONCLUSIONS: The present case emphasizes that it is difficult to make an accurate preoperative diagnosis with the presentation of hidden malignancy, such as hydronephrosis.

A Propensity Score-Matched Comparison Between Sutureless and Suture Techniques in Laparoscopic Nephron-Sparing Surgery: A Retrospective Non-Randomized Observational Study.

Objective: To compare the surgical feasibility, oncological and functional results between sutureless and suture techniques in retroperitoneal laparoscopic nephron-sparing surgery (LNSS). Materials and Methods: This retrospective study collected consecutive patients with a renal mass who underwent retroperitoneal LNSS in two high-volume centers. Propensity score matching (PSM) analysis was conducted to select two baseline homogeneous cohorts. Descriptive statistics was performed both before and after PSM. Moreover, univariate and multivariate logistic analyses were carried out to identify the risk factors of postoperative acute kidney injury (AKI), whereas Kaplan-Meier analysis for functional deterioration (new-onset stage 3 chronic kidney disease [CKD], estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2, or CKD upstaging after surgery) was utilized to compare the two cohorts. Results: After PSM at a ratio of 1:3, the sutureless group (n = 65) was compared with the suture group (n = 152) with no remaining statistically significant differences in baseline characteristics. With regard to patient outcomes, differences in warm ischemia time (WIT) (P < .001), estimated blood loss (P < .001), AKI (P = .002), length of hospital stay (P = .020), and eGFR at discharge (P < .001) were statistically significant. Meanwhile, the postoperative complication rates (9.2% versus 13.8%, P = .378) and positive surgical margins (0% versus 2.0%, P = .556) were not statistically different. At the last follow-up, the eGFR decline percent was the same (-1.5% versus -2.2%, P = .192). No difference was detected on Kaplan-Meier analysis for functional deterioration (log-rank test, P = .304). Conclusions: Sutureless technique in LNSS is safe and feasible, compared with the traditional suture method, with shorter WIT, lower AKI rate, and comparable long-term oncological and functional outcomes.

A Combination of the Mayo Adhesive Probability Score and the RENAL Score to Predict Intraoperative Complications in Small Renal Masses.

INTRODUCTION: To evaluate the potential predictive value of the Mayo Adhesive Probability (MAP) score combined with the RENAL score for intraoperative outcomes in retroperitoneal laparoscopic nephron-sparing surgery (NSS) in an Eastern Asian population. METHODS: An initial of 388 patients undergoing retroperitoneal laparoscopic NSS were identified. MAP and RENAL scores were calculated according to CT and a logistic regression model was adopted as a combination of the RENAL score and the MAP score. RESULTS: A total of 293 patients were included. The overall intraoperative complication rate was 7.5% (21 cases). The MAP score was found to correlate with operation time (OT; r = 0.169), estimated blood loss (EBL; r = 0.318), and intraoperative complications (r = 0.242). The RENAL score was correlated with warm is-chemia time (r = 0.503), OT (r = 0.334), intraoperative complications (r = 0.178), and EBL (r = 0.218). The MAP score and the RENAL score were reliable predictors of overall intraoperative complications, with areas under the curve (AUC) of 0.728 and 0.759, respectively. After combination of these 2 scores, the AUC of overall intra-operative complications was improved with statistical significance (AUC = 0.847, combination vs. RENAL score: p = 0.044 < 0.05; combination vs. MAP score: p = 0.005 < 0.05). CONCLUSION: The MAP score is an important predictor of EBL, OT, and intraoperative complications in retroperitoneal laparoscopic NSS and its combination with the RENAL score showed a superior predictive value compared to a single score in overall intraoperative complications. The MAP score might be considered in preoperative radiologic aspects as regularly as the RENAL score.

Gene expression profile determination in rat retinal tissue after ocular hypertension through oligo microarray.

Increased intraocular pressure is the main cause of glaucoma development. However, the systemic information of genes related to ocular hypertension has not yet been clarified. In the present study, oligomicroarray determined the profile of gene expression in the retina after ocular hypertension. A rat ocular hypertension model was constructed through photocoagulation by diode lasers. On postoperative days 7, 35, 60, 90, 180 and 360, the intraocular pressure and the gene expression profile were determined using an ophthalmotonometer and an Oligochip containing 35,000 oligonucleotides, respectively. Oligochip reliability was verified by real-time PCR, and the Oligochip data were analyzed through functional distribution analysis. In our study, we found that the intraocular pressure was significantly increased in a time-dependent manner but returned to the normal level on postoperative day 360. We also found that 1,692 genes were differentially expressed, including 719 upregulated and 973 downregulated genes. The χ² value of gene clusters related to transport function is significantly higher than that of other gene clusters as determined through function distribution analysis, suggesting that this group of genes plays an important role in the repair process of the optical nerve. In conclusion, the gene expression pattern at different time points of ocular hypertension was determined, which may contribute to clarify the molecular mechanism of glaucoma and to establish better therapeutic strategies to treat glaucoma.

Management of complete ureteral avulsion and literature review: a report on four cases.

OBJECTIVE: The aim of this study was to investigate the treatment modality of complete ureteral avulsion. PATIENTS AND METHODS: This study retrospectively analyzed the data of four patients with complete ureteral avulsion who were treated between November 2003 and March 2008 in our hospital. Of the four patients, one had ureteropelvic junction avulsion, one had proximal ureteral avulsion, and the other two had distal ureteral avulsion. One patient underwent autotransplantation of kidney for treatment of severe proximal ureteral avulsion. Pyeloureterostomy plus greater omentum investment outside the native distal ipsilateral ureter was performed in the patient with ureteropelvic junction avulsion. The other two patients underwent ureterovesical anastomosis. All four patients were followed up for an average time of 29 months (16-45 months). RESULTS: Renal function recovered well in the patient who underwent autotransplantation of kidney and ureterovesical anastomosis and the two patients who underwent ureterovesical anastomosis. The other patient who underwent pyeloureterostomy developed hydronephrosis and nonfunctioning kidney. The patient then underwent nephrectomy. CONCLUSIONS: Complete ureteral avulsion is a rare but severe complication. Autotransplantation of kidney and ureterovesical anastomosis may result in positive outcomes in patients with proximal ureteral avulsion.

Administration of dendritic cells dual expressing DcR3 and GAD65 mediates the suppression of T cells and induces long-term acceptance of pancreatic-islet transplantation.

Pancreatic-islet transplantation is currently regarded as the only approach to cure type 1 diabetic patients (T1D). However, recurrent autoimmunity is a critical factor contributing to graft rejection along with alloreactivity. Recently, the glutamic acid decarboxylase 65 (GAD65) was identified as the one of the major pancreatic antigens targeted by self-reactive T cells in T1D. Therefore, the T cells specific for GAD65 may be the important therapeutical target of T1D. In this study, dendritic cells (DCs) were transfected with the recombinant adenovirus, dual expressing DcR3 and GAD65 in vitro, and NOD mice were administrated with the genetically modified DCs in vivo after islet transplantation. The results demonstrated that the genetically modified DCs significantly suppressed the T cell response to GAD65, delayed onset of diabetes, improved the success and survival of islet transplantation. The findings suggest that the adoptive transfer of genetically modified DCs dual expressing DcR3 and GAD65 represent a future therapeutic potential in T1D and pancreatic-islet transplantation.

Construction of a DNA vaccine encoding Flk-1 extracellular domain and C3d fusion gene and investigation of its suppressing effect on tumor growth.

Although the critical role of complement component C3d as a molecular adjuvant in preventing virus infection is well established, its role in cancer prophylaxis and treatment is unclear. In this study, we constructed a recombinant plasmid encoding Flk-1 and C3d3 fusion proteins and investigated its transient expression in vitro in transfected eukaryotic cells and its antibody response in immunized mice. Subsequently, we investigated the vaccine's ability to elicit an immune response leading to suppression of angiogenesis and tumor growth in mice bearing bladder transitional cell carcinoma. Using Western blotting, immunocytochemistry, and flow cytometry, we detected the expression of Flk-1 and C3d3 fusion proteins in COS-7 cells transfected with these recombinant plasmids. Further binding experiment using CR2 (C3d receptor) positive Raji cells that were incubated with transfected COS-7 supernatant indicated that C3d was successfully fused to Flk-1. Although both vaccines elicited peak antibody levels at 5 weeks, Flk-1-specific antibody titer in pSG.SS.Flk-1(ECD).C3d3.YL-immunized mice was significantly higher when compared to pSG.SS.Flk-1(ECD).YL-immunized mice. The results of experiments with bladder tumor-bearing mice showed that the vaccine inhibited tumor growth significantly. These results suggest that C3d plays a critical role in tumor immunotherapy by promoting antibody response in Flk-1-based DNA vaccines. This approach may provide a new strategy for the rational design of anti-angiogenic therapies for the treatment of solid tumors and provide a basis for the further exploitation and application of the anti-angiogenesis DNA vaccines.