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Upper urinary tract stones are very common in my country, with an incidence of 1% to 5% in the North and an even higher incidence of 5% to 10% in the south. The incidence rate in the south is higher than that in the north, mainly due to the water quality, climate and eating habits of the region. From the perspective of sex, incidence is more likely in males than females. In the high-incidence population, young adults are most prone to stones. Men in the age range of 25 to 40 years are more likely to have stones.To observe the therapeutic effect of minimally invasive percutaneous nephrolithotomy (mPCNL) on upper urinary tract stones and its influence on the renal function of patients.Patients with upper urinary tract stones who were treated in our hospital from February 2017 to March 2018 were selected as research subjects and were divided into the PCNL group and the mPCNL group according to the random number table method. The general conditions of the two groups of patients were observed during the perioperative period, and the differences in stone clearance, pain, renal function indicators and complication rates were compared between the two groups to determine which were statistically significant (The operation time of the mPCNL group was longer than that of the PCNL group (mPCNL has a good therapeutic effect on upper urinary tract stones, with a high stone clearance rate without causing kidney damage or increasing the incidence of complications, and thus has good application value.

Prostate cancer is the second most common cancer in men worldwide1. Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing its genetic and epigenetic landscape in thousands of patients2,3. However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1. Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease.

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P0.01) and csPCa (0.937 vs 0.845, P0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.

ImportanceDelayed graft function (DGF) is a risk factor for acute rejection and graft failure after kidney transplant. Previous studies have suggested that dexmedetomidine may be renoprotective, but whether the use of dexmedetomidine would improve kidney allograft function is unknown.ObjectiveTo investigate the effects of perioperative dexmedetomidine on DGF following a donation-after-cardiac-death (DCD) kidney transplant.Design, setting, and participantsThis single-center, double-blind, placebo-controlled randomized clinical trial was conducted at The First Affiliated Hospital of Soochow University in Suzhou, China. Adults (18 years or older) who were scheduled for DCD kidney transplant were enrolled between September 1, 2019, and January 28, 2021, and then randomized to receive either dexmedetomidine or normal saline (placebo). One-year postoperative outcomes were recorded. All analyses were based on the modified intention-to-treat population.InterventionsPatients who were randomized to the dexmedetomidine group received a 24-hour perioperative dexmedetomidine intravenous infusion (0.4 μg/kg/h intraoperatively and 0.1 μg/kg/h postoperatively). Patients who were randomized to the normal saline group received an intravenous infusion of the placebo with the same dose regimen as the dexmedetomidine.Main outcomes and measuresThe primary outcome was the incidence of DGF, defined as the need for dialysis in the first posttransplant week. The prespecified secondary outcomes were in-hospital repeated dialysis in the first posttransplant week, in-hospital acute rejection, and serum creatinine, serum cystatin C, estimated glomerular filtration rate, need for dialysis, and patient survival on posttransplant day 30.ResultsOf the 114 patients enrolled, 111 completed the study (mean [SD] age, 43.4 [10.8] years; 64 male patients [57.7%]), of whom 56 were randomized to the dexmedetomidine group and 55 to the normal saline group. Dexmedetomidine infusion compared with normal saline reduced the incidence of DGF (17.9% vs 34.5%; odds ratio [OR], 0.41; 95% CI, 0.17-0.98; P = .04) and repeated dialysis (12.5% vs 30.9%; OR, 0.32; 95% CI, 0.13-0.88; P = .02, which was not statistically significant after multiple testing corrections), without significant effect on other secondary outcomes. Dexmedetomidine vs normal saline infusion led to a higher median (IQR) creatinine clearance rate on postoperative days 1 (9.9 [4.9-21.2] mL/min vs 7.9 [2.0-10.4] mL/min) and 2 (29.6 [9.7-67.4] mL/min vs 14.6 [3.8-45.1] mL/min) as well as increased median (IQR) urine output on postoperative days 2 (106.5 [66.3-175.6] mL/h vs 82.9 [27.1-141.9] mL/h) and 7 (126.1 [98.0-151.3] mL/h vs 107.0 [82.5-137.5] mL/h) and at hospital discharge discharge (110.4 [92.8-121.9] mL/h vs 97.1 [77.5-113.8] mL/h). Three patients (5.5%) from the normal saline group developed allograft failure by the post hoc 1-year follow-up visit.Conclusions and relevanceThis randomized clinical trial found that 24-hour perioperative dexmedetomidine decreased the incidence of DGF after DCD kidney transplant. The findings support the use of dexmedetomidine in kidney transplants.Trial registrationChinese Clinical Trial Registry Identifier: ChiCTR1900025493.

Laparoscopy surgery is the gold standard for the treatment of aldosterone-producing adenomas (APA). However, the effectiveness between laparoscopic total and partial adrenalectomy is controversial. Therefore, we retrospectively analyzed the postoperative and follow-up outcomes of these two procedures.A total of 96 APA patients underwent laparoscopic surgery in our hospital between January 2012 and December 2017. A total of 65 patients who underwent laparoscopic partial adrenalectomy (group 1) were compared with 31 patients who underwent laparoscopic total adrenalectomy (group 2). The mean follow-up time was 32.3 months and 40.8 months, respectively. Patient's preoperative characteristics, date during surgery, and postoperative clinical results of the two groups were analyzed.In both groups of patients, laparoscopic adrenalectomy was successfully carried out. The laparoscopic partial adrenalectomy group had a shorter operation time when compared to total adrenalectomy (P = .01). However, patients in the laparoscopic total adrenalectomy group were older (P = .04) and had a higher proportion of multiple adenomas (P = .01) compared to partial adrenalectomy. Five patients (7.7%) who underwent partial adrenalectomy did not show improvement in hypertension and/or serum potassium below normal levels, and review of plasma aldosterone concentration (PAC) and/or computerized tomography (CT) indicated that surgery was not successful in these patients. All 31 patients who underwent total adrenalectomy showed improvement or recovery from hypertension, and all PAC and serum potassium levels returned to normal levels after surgery.Although both surgical procedures were technically safe and feasible, laparoscopic partial adrenalectomy showed a higher failure rate (7.7%) for patients with APA. Therefore, choosing laparoscopic partial adrenalectomy requires careful consideration, and we selected laparoscopic total adrenalectomy in patients with unilateral APA.

Transitional cell carcinoma (TCC) is the one of the most commonly observed types of cancer globally. The identification of novel disease-associated genes in TCC has had a significant effect on the diagnosis and treatment of bladder cancer; however, there may be a large number of novel genes that have not been identified. In the present study, the exomes of two individuals who were diagnosed with muscle-invasive TCC (MI-TCC) were sequenced to investigate potential variants. Subsequently, following algorithm and filter analysis, Sanger sequencing was used to validate the results of deep sequencing. Immunohistochemistry (IHC) was employed to observe the differences in HECT, C2 and WW domain-containing E3 ubiquitin protein ligase 1 (HECW1) protein expression between tumor tissues and para-carcinoma tissues. A total of 6 nonsynonymous mutation genes were identified in MI-TCC, identified as copine VII, RNA binding motif protein, X-linked-like 3, acyl-CoA synthetase medium-chain family member 2A, HECW1, zinc finger protein 273 and trichohyalin. Furthermore, 5 cases were identified to possess a HECW1 gene mutation in 61 MI-TCC specimens, and all of these were point mutations located at exon 11 on chromosome 7. The mutation categories of HECW1 had 4 missense mutations and 1 nonsense mutation. IHC revealed that HECW1 protein was expressed at significantly increased levels in MI-TCC compared with normal bladder urothelium (P

Cryopreservation brings sublethal damage to sperm, resulting in reduced fertile life of sperm. Rhodiola rosea polysaccharides (RPs) have antiviral, antioxidant and antitumor activities. In the present study, the cryoprotective effect of RPs on boar sperm quality parameters after frozen-thawed process was investigated. Boar sperm was cryopreserved in the extender with RPs added at concentrations of 0 (used as control), 2, 4, 6, 8 and 10mg/L and their effects on the quality of frozen-thawed boar sperm were assessed. Addition of RPs significantly improved sperm motility, mitochondrial activity, acrosomal integrity, plasma membrane integrity, superoxide dismutase and glutathione peroxidase activity and decreased sperm malonaldehyde level (p

To investigate the effects of cynomorium songaricum (CS) decoction on the testis weight, serum testosterone level, and sperm parameters of rats with oligoasthenospermia (OAS), explore its action mechanism of improving the proliferation of undifferentiated spermatogonial cells, and provide some experimental and theoretical evidence for the development of new Chinese drugs for OAS.Thirty 8-week-old male SD rats were randomly divided into five groups of equal number: blank control, model control, high-dose CS, medium-dose CS, and low-dose CS. OAS models were established by intraperitoneal injection of cyclophosphamide and, a month later, treated intragastrically with normal saline or CS at 2, 1, and 0.5 g per kg of the body weight per day, all for 4 weeks. Then, the testes of the animals were harvested to obtain the testicular weight, sperm concentration and motility, and the level of serum testosterone (T), detect the expressions of the transcription factor 1 (Oct4), Thy-1 cell surface antigen (Thy1), promyelocytic leukemia zinc finger (PLZF), KIT proto-oncogene receptor tyrosine kinase (C-kit) and glial cell-derived neurotrophic factor (GDNF) in the testis tissue of the rats in the low-dose CS group by real-time PCR.The testis weights in the blank control, model control, high-dose CS, medium-dose CS, and low-dose CS groups were (1.52±0.06), (1.55±0.06), (1.43±0.30), (1.35±0.40) and (1.34±0.04) g, respectively, not significantly different in the blank and model controls from those in the CS groups (P0.05). The visual field sperm count per 10 HP was significantly increased in the high-, medium-, and low-dose CS groups (202±20, 196±5 and 216±25) as compared with the blank and model controls (200±15 and 134±30) (P0.05). The mRNA expressions of the Oct4, Thy1, PLZF and GDNF genes were remarkably higher in the low-dose CS group than in the controls (P0.05), but that of the C-kit gene showed no significant difference from the latter (P0.05). The visual field sperm motility per 10 HP was markedly increased in the blank control (［52.1±5.5］%), model control (［38.1±2.5］%), high-dose CS (［59.1±9.5］%), medium-dose CS (［58.7±9.5］%), and low-dose CS (［49.6±1.0］%) groups, and so was the level of serum testosterone (［190±87.5］, ［82.5±25.8］, ［229±75.6］, ［331±86.7］ and ［185±82.4］ mmol/L), both remarkably higher in the CS groups than in the model controls (P0.05) but with no statistically significant difference between the CS groups and the blank controls (P0.05).CS can significantly improve sperm concentration, sperm motility and serum T level in OAS rats, probably by inducing the expression of GDNF in the rat Sertoli cells, promoting the proliferation of undifferentiated spermatogonial cells, and enhancing spermatogenesis.目的： 探究锁阳对少、弱精子症大鼠睾丸重量、血清睾酮浓度、以及精子数量、活动率等精子参数的影响，及促进未分化精原细胞增殖的机制，为开发新的治疗男性少、弱精子症的中药提供实验和理论依据。方法： 选取8周龄，体重约(220±10) g的SD大鼠30只，随机分为5组（n=6）：空白对照组、模型对照组、3组实验组（低、中、高锁阳浓度剂量）；将模型对照组与锁阳实验组予以环磷酰胺［30 mg/（kg·d）］腹腔注射，连续5 d，构建大鼠少、弱精子症模型；将3组实验组分别用低浓度［0.5 g/（kg·d）］、中浓度［1 g/（kg·d）］及高浓度［2 g/（kg·d）］锁阳水煎液灌胃，每天1次，连续4周后观察各组精子数量、活动率，测量各组大鼠血清睾酮浓度，并取各组大鼠睾丸称重；采用Real-time PCR方法检测低浓度组睾丸组织中精原干细胞标志物（Oct4、Thy1、PLZF、C-kit）表达情况，采用β-actin作为内参；采用Real-time PCR方法检测低浓度组睾丸组织中胶质细胞源性神经营养因子(GDNF)表达情况。结果： 空白对照组、模型对照组及低、中、高浓度锁阳实验组的大鼠睾丸重量分别为(1.52±0.06) g、(1.55±0.06) g、(1.34±0.04) g、(1.35±0.40) g、(1.43±0.30) g，不同浓度锁阳实验组大鼠睾丸重量与空白对照组、模型对照组比较未见明显差异（P0.05）。空白对照组、模型对照组及低、中、高浓度实验组在每10个高倍镜视野精子数（精子数/10HP）分别为200±15、134±30、216±25、196±5、202±20个,锁阳实验组与模型对照组比较可显著提高大鼠的精子数量（P0.05）；低浓度锁阳水提物组睾丸组织中Oct4、Thy1、PLZF、GDNF基因mRNA表达水平较模型对照组增加，差异有统计学意义（P0.05），C-kit基因mRNA表达水平未见明显差异（P0.05）; 空白对照组、模型对照组及低、中、高浓度锁阳实验组的大鼠每10个高倍镜视野精子活动率（精子活动率/10HP）分别为(52.1±5.5)%、(38.1±2.5)%、(49.6±1.0)%、(58.7±9.5)%、(59.1±9.5)%；大鼠血清睾酮浓度分别为(190.0±87.5)、(82.5±25.8)、(185.0±82.4)、(331.0±86.7)、(229.0±75.6) mmol/L，锁阳实验组与模型对照组比较可显著提高大鼠的精子活动率及血清睾酮浓度（P均0.05），但与空白对照组比较无明显差异(P0.05)。结论： 锁阳能显著提高少、弱精子症大鼠的精子数量、精子活动能力、血清睾酮水平，其改善机制可能是：①通过诱导睾丸Sertoli细胞中GDNF表达，促进未分化精原细胞增殖，从而促进精子发生过程，增加附睾尾部精子数目；②通过促进睾酮分泌，提高血清睾酮水平，进而改善精子活动率。.

Introduction Polymorphisms in the prostate stem cell antigen (PSCA) gene have been hypothesized to increase the genetic susceptibility to cancers. The common sequence variation in PSCA rs2294008 (C>T) has been implicated in cancer risk. However, results of the relevant published studies were somewhat underpowered and controversial in general.

Dysregulation of Maspin expression and constitutive activation of NF-κB subunits are important events in tumorigenesis of prostate cancer. Recent finding points that RelB, which contributes to the alternative NF-κB activity, interferes with carcinogenesis in the prostate. We report here, that both the classical and the alternative NF-κB activities are constitutively present in androgen-insensitive human prostate cancer cells. Maspin and RelB expression is correlated negatively in prostate cancer tissues at the later stage. TNF-α signaling triggers the nuclear accumulation of RelB and the concomitant reduction of Maspin expression in a time-dependent manner. In addition, the proteasome inhibitor-induced Maspin expression is accompanied by the reduction of RelB expression. A successful depletion of RelB expression, but not RelA expression, induces Maspin expression. RelB-deficiency abrogates the proteasome inhibitor-induced Maspin expression. Moreover, we demonstrate that the enforced expression of RelB protein in prostate cancer cells inhibits Maspin expression. We propose that RelB is an essential molecule controlling the endogenous and the proteasome inhibitor-induced Maspin expression. Developing a RelB-targeted therapeutic intervention, which might be coupled with the induction of a tumor suppressor Maspin, is valuable in treating advanced, metastatic prostate cancer.

Objective The aim of the study was to investigate the expressions of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of MMP-2 (TIMP-2) mRNA in transitional cell carcinomas of bladder and discuss their clinical significances.

Dendritic cells (DC) are key factors in regulating immune responses, and they induce immune response or tolerance depends on its maturation states. Previous studies demonstrated that blocking IKK2 in bone marrow-derived dendritic cells (BMDC) by adenoviral transfection with a kinase-defective dominant negative form of IKK2 (IKK2dn) could inhibit NF-kappaB activation and impair DC maturation. Here, we transfected IKK2dn into recipient rat (Lewis) BMDC by adenovirus vector (Adv-IKK2dn-DC) and found that Adv-IKK2dn-DC had reduced B7-2 and B7-1 expression under alloantigen stimulation. Their ability to induce allogeneic T-cell proliferation was markedly reduced in comparison with uninfected DC. A higher IL-10 secretion and a lower IFN-gamma secretion were detected in Adv-IKK2dn-DC-stimulated allogenic T cells. Furthermore, we showed that Adv-IKK2dn-DC pulsed with BN (Brown Norway rats) splenocyte lysates markedly prolonged the survival of renal allografts in an antigen-specific manner. These findings suggested that Adv-IKK2dn-DC loaded with BN antigen could suppress anti-alloimmune response and induce tolerance to allografts, which provided an experimental base for immune tolerance induction by recipient DC loaded with donor antigens. Our finding may provide a more feasible strategy for deceased-donor renal transplantation.

Objective To establish an orthotopic bladder cancer model bearing human bladder cancer for experimental research, and monitor tumor progression by magnetic resonance imaging (MRI).

The objective of this study was to investigate the possible association of the ABCB1 gene C3435 T polymorphism and the CYP3A5 gene A6986G polymorphism with sirolimus (SRL) trough concentration and dose requirements in Chinese stable renal transplant recipients. Blood samples were collected from 105 healthy volunteers and 50 renal transplant patients, whose polymorphisms of the ABCB1 and CYP3A5 genes were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Plasma concentrations of SRL were determined with HPLC. The allele frequencies of the ABCB1 mutation in Chinese healthy volunteers and renal transplant recipients were 51.0% and 44.0% (p0.05), while the allele frequencies of the CYP3A5 mutation were 72.9% and 71.0% (p0.05). The SRL concentration/dose ratio (C/D) in patients with CYP3A5 (*)3/(*)3 were significantly higher than that of those with (*)1 allele (p0.05). However, no significant differences were observed between C/D and ABCB1 SNPs (p0.05). These results confirm that when treated with a SRL-based therapy and low-dose steroids, patients carrying the CYP3A5(*)1 allele required significantly more SRL to achieve adequate blood trough concentrations. In patients with SRL-based therapy, genotyping of the CYP3A5 genes may help to optimize the SRL management in renal transplant recipients.

The present study was performed to investigate the effect of retinoic acid fluoro chalcone (RAFC) on lipopolysaccharide (LPS) induced epithelial-mesenchymal transition (EMT) in PC3 and CWR22rv1 prostate cell lines. Lipo-polysaccharide (LPS) was used to induce epithelial-mesenchymal transition in prostate carcinoma cell lines. The results revealed that treatment of PC3 and CWR22rv1 cells with LPS resulted in significant changes in the morphological features of the EMT. The mesenchymal marker, vimentin expression was significantly increased whereas the expression level of E‑cadherin was markedly decreased after the treatment. We also observed increased cell motility and higher level of transcription factor glioma‑associated oncogene homolog 1 (Gli1) expression on LPS treatment. Treatment of prostate cells with RAFC reversed the morphological changes induced by LPS in prostate cells. RAFC also reduced the expression of EMT markers induced by LPS and suppressed the Gli1 expression. The resultant effect of these changes was the suppression of motility and invasiveness of the prostrate cells. Thus, RAFC exhibited anti‑invasive effect on prostrate cells by inhibition of the EMT process via Hedgehog signaling pathway.

BACKGROUND Bladder cancer is the most common type of urinary system tumours. It is frequently associated with genetic mutations that deregulate the cell cycle and render these tumours resistant to apoptosis. Survivin, a newly discovered member inhibitor of apoptosis protein (IAP) family in several human cancers, by inducing cell proliferation and inhibiting apoptosis is frequently activated in bladder cancer. We studied the influence of small interfering RNA (siRNA) targeting survivin on the biological behaviour of bladder cancer cells. METHODS A double strand survivin target sequence specific siRNA was designed and synthesized. After transfection of bladder cancer cell line T24 by siRNA/liposome complex with increasing concentrations (50200 nmol/L), the transfectant cells were intratumourally injected at different doses (5 microg or 50 microg). The effects were measured in vitro and in vivo. RESULTS The selected siRNA efficiently down-regulated survivin mRNA expression in a dose and time dependent manner. The maximal effect was achieved at the concentration of 100 nmol/L, at which survivin expression level was down-regulated by 75.91%. The inhibition rate of cell growth was 55.29% (P < 0.01) and the markedly increased apoptotic rate was 45.70% (P < 0.01). In vivo intratumoural injection of 50 microg siRNA-survivin could notably prevent the growth of bladder cancer (P < 0.01) in xenografted animals. CONCLUSION The application of siRNA-survivin could markedly inhibit survivin expression in bladder cancer cell line by inducing apoptosis and inhibiting the growth of the tumour. It may become a new gene therapy tool for bladder cancer.

Bladder cancer is the most malignant cancer of the urinary system. However a noninvasive and sensitive method of the early diagnosis for bladder cancer has not been developed. This study was to explore the expression of survivin mRNA in urine exfoliated cells of preoperative and postoperative patients with bladder transitional cell carcinoma (BTCC), and to analyze its value in early diagnosis and postoperative monitoring.Urine of 30 patients with initially diagnosed BTCC was collected before operation and one week, one month, six months and 15 months after operation. Urine of 10 healthy volunteers and 15 patients with cystitis was used as control. Expression of survivin mRNA in urine exfoliated cells was detected by real-time fluorescent quantitative polymerase chain reaction (real-time PCR).The relative copy number of survivin mRNA in the patients was (96.01+/-42.33) before operation, which was significantly higher than that of healthy volunteers and cystitis patients (P0.05). The level of survivin mRNA was apparently declined one week after operation (25.30+/-1.51) compared with its preoperative level (P0.05); and the level became as low as the control group after one month (13.20+/-1.49) and six months (13.90+/-1.36) (P0.05). Patients were followed up for 15 months, and three patients recurred, whose survivin mRNA level (97.83+/-27.47) was significantly higher than that at six months after operation (P0.05).Detecting survivin mRNA in urine exfoliated cells is sensitive for the diagnosis of BTCC. Detection survivin mRNA after operation can monitor recurrence.

Humoral immunity is an important factor for long-term survival of renal allograft. Here we performed a four-year follow-up to explore the clinical significance of monitoring anti-human leukocyte antigens (HLA) and anti-major histocompatibility complex class I-related chain A (MICA) antibody expression after kidney transplantation.We obtained serial serum samples from 84 kidney transplant patients over a four-year period. All patients were followed up at least 6 months after transplantation and had at least two follow-up points. Anti-HLA and anti-MICA antibody titres and serum creatinine (SCr) levels were evaluated at each follow-up. Patients were divided into 4 groups: HLA(+) MICA(-), HLA(-)MICA(+), HLA(+)MICA(+) and HLA(-)MICA(-). The impact of post-transplant antibody level on kidney allograft function was evaluated.Antibodies were detected in 38.1% (32/84) of the renal allograft recipients. HLA, MICA and HLA+MICA expression was observed in 18.89%, 14.44% and 5.93% of the recipients respectively. The most frequent anti-HLA and anti-MICA specific antibodies identified were A11, A24, A29, A32, A33, A80; B7, B13, B37; DR17, DR12, DR18, DR52, DR53, DR1, DR4, DR9, DR51; DQ7, DQ4, DQ8, DQ2, DQ9, DQ5, DQ6 and MICA02, MICA18, MICA19, MICA07, MICA27. As the time after transplantation elapsed, more recipients developed de novo antibody expression. Total 11.91% (10/84) of the recipients had de novo antibody expression during the follow up. The average level of SCr and the percentage of recipients with abnormal allograft function were significantly higher in recipients with anti-HLA and/or anti-MICA antibody expression than those without. The appearance of anti-HLA and anti-MICA antibody expression always preceded the increase in SCr value.Anti-HLA and anti-MICA antibody expression has predictive value for early and late allograft dysfunction. The presence of donor specific antibody is detrimental to graft function and graft survival.

Previous studies have demonstrated that recipient-derived immature dendritic cells transfected by recombinant adenovirus-mediated IKK2dn (Adv‑IKK2dn) and loaded with donor splenocyte lysate generate CD4+CD25- T cells (Adv-IKK2dn-CD4+CD25- T cells). These cells may inhibit T cell responses in vitro. In the present study, Lewis (LW) rats were administered with an intravenous injection of naive CD4+ T cells, empty adenovirus (Adv-0)-dendritic cell-generated CD4+CD25- T cells (Adv-0-CD4+CD25- T cells), Adv-IKK2dn-CD4+CD25- T cells or an equal volume of normal saline, seven days prior to transplantation. The potency and the mechanism of action of Adv-IKK2dn-CD4+CD25- T cells was analyzed, as well as an investigation of their tolerogenic properties in vivo. Administration of Adv-IKK2dn-CD4+CD25- T cells in vivo to LW rats was observed to markedly prolong the survival of a kidney allograft from Brown Norway rats. Furthermore, the Adv-IKK2dn-CD4+CD25- T cell-treated group exhibited significantly reduced levels of interleukin (Il)-2 and interferon-γ production and increased Il-10 and transforming growth factor-β (TGF-β) secretion. The serum creatinine levels remained at low levels in the Adv-IKK2dn-CD4+CD25- T cell-treated group. Their ability to induce allogeneic T cell proliferation was markedly reduced compared with the other groups. These observations indicated that Adv-IKK2dn-CD4+CD25- T cells induce prolongation of kidney allograft survival in vivo, which is hypothesized to be due to the high expression levels of Il-10 and TGF-β.

To investigate the effects of the downregulated expression of the prostate androgen regulated (PAR) gene on the cell cycle and apoptosis of PC3 cells as well as on the expression level of Bcl-2/Bax.After transfecting PC3 cells with small interfering RNA (siRNA) targeting PAR, we detected the inhibitory effect of PAR depletion on the proliferation of the PC3 cells by MTT assay, determined their apoptosis by flow cytometry, and measured the expression levels of Bcl-2 and Bax by Western blot.The expression of PAR was suppressed by siRNA, the G2-M phase PC3 cells were increased to (29.95 +/- 3.25)%, and the apoptosis of the cells was enhanced to (20.61 +/- 2.73)%, with statistically significant difference from the control group (P0.01). Western blot showed a decreased expression of Bcl-2, an increased expression of Bax, and an elevated ratio of Bax to Bcl-2.Downregulation of the PAR expression increases the Bax/Bcl-2 ratio and Bax expression, and thus induces the G2-M phase arrest and apoptosis of PC3 cells.

Background: Prostate cancer (Pca) is one of the most common complex and polygenic diseases in men. The X-ray repair complementing group 1 gene (XRCC1) is an important candidate in the pathogenesis of Pca. The purpose of this study was to evaluate the association between single nucleotide polymorphisms in the XRCC1 gene and susceptibility to Pca. Materials and Methods: XRCC1 gene polymorphisms and associations with susceptibility to Pca were investigated in 193 prostate patients and 188 cancer-free Chinese men. Results: The c.910A>G variant in the exon9 of XRCC1 gene could be detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods. Significantly increased susceptibility to prostate cancer was noted in the homozygote comparison (GG versus AA: OR=2.95, 95% CI 1.46-5.42, χ 2 =12.36, P=0.001), heterozygote comparison (AG versus AA: OR=1.76, 95% CI 1.12-2.51, χ2=4.04, P=0.045), dominant model (GG/AG versus AA: OR=1.93, 95% CI 1.19-2.97, χ2=9.12, P=0.003), recessive model (GG versus AG+AA: OR=2.17, 95% CI 1.33-4.06, χ2=8.86, P=0.003) and with allele contrast (G versus A: OR=1.89, 95% CI 1.56-2.42, χ2=14.67, P G polymorphism of the XRCC1 gene is associated with susceptibility to Pca in Chinese men, the G-allele conferring higher risk.

Retrograde ureteroscopic marsupialization is a pure natural orifice translumenal endoscopic surgery (NOTES). We retrospectively examined the feasibility and safety of this technique to manage symptomatic simple renal cysts.Sixteen patients with simple renal cysts were selected and treated by incising the cyst wall to drain into the collecting system through retrograde ureteroscopy. A retrospective observational study was performed to evaluate the patient's symptomatic and radiologic results after ureteroscopic marsupialization. Symptomatic success based on pain relief was evaluated using a visual analog pain scale preoperatively and postoperatively. Radiologic success was defined as no recurrence of the cyst or a reduction in cyst size by at least half.There were no intraoperative or postoperative complications observed. The mean operative time was 35 minutes (range 20-50 min). The mean hospital stay was 3.4 days (range 2-5 d). Of the 16 patients, one patient was lost at follow-up. The symptoms based on pain had resolved in 13 (83%) cases but remained in 2 cases at a mean follow-up of 24.2 months (range 6-36 mos). The average visual analog pain scale decreased from 6.7 (range 4-9) to 1.1 (range 0-5) at the sixth month. The mean size of all cysts decreased from 6.8 cm (range 4-10 cm) to 1.3 cm (range 0-5 cm). Radiographic success was achieved in 93% (14/15) of patients. Cytology and cyst wall pathology reports revealed no evidence of malignancy.Retrograde ureteroscopic marsupialization is a complete transurethral NOTES marsupialization. With appropriate patient selection, the minimally invasive retrograde ureteroscopic marsupialization is feasible, safe, and effective. It can be preferred to more invasive laparoscopic or open surgical approaches.

To study the protection of gene transfer-induced human heme oxygenase-1 over-expression against renal ischemia reperfusion injury in rats.The model of kidney ischemia-reperfusion injury was established with Sprague-Dawley rats. In the therapy group (n=18), the left kidney was perfused and preserved with Ad-hHO-1 at 2.5×10(9) pfu/1.0 ml after flushed with 0-4°C HC-A organ storage solution via donor renal aorta. The rats in control groups were perfused with 0.9% saline solution (n=12) or the vector carrying no interest gene Ad-EGFP 2.5×10(9) pfu/1.0 ml (n=18) instead of Ad-hHO-1. BUN and Cr in serum were measured by slide chemical methods. The kidney samples of rats were harvested for assay of histology, immunohistochemistry and quantification of HO enzymatic activity. Apoptosis cells in the kidney were measured by TUNEL.Ad-hHO-1 via donor renal aorta could transfect renal cells of rats effectively, enzymatic activity of HO in treated group [(1.62±0.07) nmol×mg(-1)×min(-1)] is higher than in control groups treated with saline solution team [(1.27±0.07) nmol×mg(-1)×min(-1)] and vector EGFP team [(1.22±0.06) nmol×mg(-1)×min(-1)] (P0.01). Immunohistochemically, we found that the rats treated with Ad-hHO-1 expressed hHO-1 in kidneys at a high level. Corresponding to this, the level of BUN and Cr, as well as the number of apoptosis cells, were decreased, and the damage in histology by HE staining was ameliorated.Over-expression of human HO-1 can protect the kidney from ischemia/reperfusion injury in rats.

BACKGROUND AND OBJECTIVE Studies on survivin over the past 5 years have shown that survivin participates in the genesis of several human cancers, including bladder cancer. Recent studies have indicated that survivin splice variants appeared to have unique subcellular localizations and functions as well. This study was to explore the roles of survivin and its two splice variants survivin-2B and survivin-DeltaEx3 in transitional cell carcinoma of bladder (BTCC). METHODS The relative amount of survivin, survivin-2B, and survivin-DeltaEx3 mRNA of fresh carcinoma tissues from 60 patients with BTCC and 12 non-cancerous bladder tissues were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR), and the relationships of their expression levels in different pathologic grades to clinical stages of bladder cancer were analyzed. The time of follow-up was 4-24 months. RESULTS Survivin, survivin-2B, and survivin-DeltaEx3 mRNA were detected in all BTCC tissues, and their relative expressions were 0.333+/-0.163, 0.056+/-0.017, and 0.124+/-0.096, respectively. In the control group,three and four samples expressed survivin and survivin-DeltaEx3 mRNA respectively, and all samples expressed survivin-2B mRNA. The expressions of survivin and survivin-DeltaEx3 mRNA were positively correlated with the pathologic grades and clinical stages (0 < r 's < 1,P < 0.05), however, survivin-2B mRNA was negatively correlated with those (-1 < r 's < 0, P < 0.05). CONCLUSION Detecting the expression levels of survivin and its two splice variants survivin-2B and survivin-DeltaEx3 mRNA in BTCC by real-time PCR could have potential values to evaluate tumor progression and recurrence rate.

To investigate an appropriate treatment for patients with upper ureteral stones,15 mm in size, by comparing the therapeutic outcomes for those undergoing retroperitoneoscopic ureterolithotomy (RPUL) and rigid ureteroscopic pneumatic lithotripsy (URSPL) retrospectively.During the study period, 81 patients with a large upper ureteral stone (15 mm) were divided into two groups. RPUL was performed with retroperitoneal approach, and the stone was removed in group A. URSPL was conducted using a rigid ureteroscope, and pneumatic probe was used for lithotripsy in group B. The patient characteristics, success rate, stone-free rate, operation time, and complications were analyzed prospectively in the two groups.The success rates of operation were 94.5% (34/36) in group A and 88.8% (40/45) in group B, but there were no significant differences between two groups (P0.05). After 4 weeks of follow-up, the stone-free rate after RPUL (100%, 34/34) and URSPL (77.5%, 31/40) groups were statistically different (P = 0.006). Furthermore, simultaneous ureterolithotomy and ureteroplasty by retroperitoneal laparoscopic surgery were performed on four patients combined with ureteral stricture. However, the mean operation time and hospital staying time after surgery in group A were longer than that in group B, and the differences were statistically significant (P0.05). The complication rate after RPUL (17.6%, 6/34) was lower than that after URSPL (20%, 8/40), but the differences were not statistically significant (P0.05).RPUL is a safe and effective treatment technique for large, impacted, upper ureteral stones15 mm in size when first-line treatments have failed or are unlikely to be effective. It can handle with combined pathologies simultaneously.

TNFR-associated factors (TRAFs) participate in diverse biological processes, such as adaptive and innate immunity, stress response, and bone metabolism. We report that all TRAFs except TRAF3 are expressed at mRNA and protein levels in B cell-derived Hodgkin's lymphoma cell lines (L428 and KM-H2). Both the classical (p50-RelA) and the alternative NF-kappaB activity (p52-RelB) are sustained in L428 and KM-H2 cells. A successful depletion of TRAF1 protein expression by means of RNA interference abrogates the anti-apoptosis activity in L428 cells. The TRAF1-deficiency reduces the classical NF-kappaB activity but not the alternative activity. The expression of the NF-kappaB targeting genes, such as ICAM-1, c-Flip, and Cyclin D1, is suppressed in the TRAF1-depleted cells. On the other hand, CD30 signaling upregulates the TRAF1 expression while reducing the expression of TRAF2 and TRAF5. Importantly, the CD30-induced alternative NF-kappaB activation is inhibited by the depletion of the TRAF1 expression. We also demonstrate that the phosphorylation of the extracellular signal-regulated kinase (ERK) upon CD30 stimulation in Hodgkin's lymphoma cells is independent of TRAF1 expression. Our data shed new light on the function of TRAF1 in B cell-derived lymphoma cells. We conclude that TRAF1 is an important molecule mediating both the CD30 signaling-dependent and independent NF-kappaB activation, which prevents the lymphoma cells from spontaneous and induced apoptosis.

To investigate the expressions of endothelial nitric oxide synthase (eNOS) and connexin 43 (Cx43) in the penile tissue of rats with diabetes mellitus induced erectile dysfunction (DMED) and their correlation with DMED.SD rat models of DM were established by intraperitoneal injection of alloxan, and 8 weeks later, apomorphine was administered to induce ED in the DM models. The expressions of eNOS and Cx43 were measured by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively.Alloxan did not influence the expressions of eNOS mRNA and Cx43 mRNA in the penile tissue. Compared with the DM models, the expression of eNOS mRNA significantly decreased in the DMED group (0.155 +/- 0.157 vs 0.508 +/- 0.242, P0.01), while that of Cx43 mRNA markedly increased (0.993 +/- 0.157 vs 0.545 +/- 0.138, P0.01), with a negative correlation between the two expressions (r = -0.987). The same results were shown by immunohistochemistry in the penile smooth muscle cells of the DMED rats.The decrease of eNOS expression in the penile tissue might play a key role in the development of ED in diabetic patients, while the accompanying compensative elevation of the Cx43 level has yet to be further studied.

To investigate the enhancing effect of all-trans retinoic acid (ATRA) on the bystander effect of the herpes simplex virus thymidine kinase(HSV-TK)/ganciclovir (GCV) against androgen unresponsive prostate cancer.The bystander effect of the HSV-TK/GCV system was measured by methyl thiazolyl tetrazolium (MTT) assay on PC-3 cells before and after ATRA treatment. The growth and the histopathology of transplant tumors were observed in 4 groups of nude mice with prostate cancer.ATRA augmented significantly the bystander effect of the HSV-TK/GCV system by reducing TK positive PC-3 cells from 50% to 30% (P0.05). HSV-TK showed an inhibiting effect, while ATRA with the HSV-TK/GCV system produced significant effect on prostate cancer 1 week earlier than the former (P0.05).ATRA can argument the in vivo and in vitro bystander effect of the HSV-TK/GCV system in the treatment of androgen unresponsive prostate cancer.

To study the influence of small interfering RNA (siRNA) targeting survivin on the biological behavior of bladder cancer.One pair of survivin target sequence-specific siRNA was designed, then siRNA/liposome complex was used to transfect bladder cancer cell line-T24. The efficiency of transfection and the apoptosis were detected by flow cytometry. The transcriptional level of survivin was analyzed using real time PCR. DNA sequence corresponding to siRNA targeting survivin was cloned into pRNAT-U6.1/Neo to produce plasmid targeting surviving.The ratio of T24 cells releasing fluorescence in total cells were 92.3%; siRNA-survivin efficiently down-regulated survivin expression (mRNA) in a dose-and time-dependent manner. Its maximal effect was achieved at the concentration of 100 nmol/L, at which survivin expression level was down regulated by 75.91%. Similar results were found in the inhibition ratio of cell growth, which was 55.29%(P0.01). Simultaneously the apoptotic rate was markedly increased, which was 45.70%(P0.01). After cutting the vector with Bam H I and Hin d III and ligating the vector with the insert by using T4 ligase, the recombinant vector was confirmed by restriction digestion and DNA sequencing.The application of siRNA-survivin can markedly inhibit survivin expression in bladder cancer cell line, induce apoptosis and inhibit the growth of the tumor. It may be a new gene therapy tool for bladder cancer. The successful construction of the siRNA expressing plasmid will facilitate the application of RNA interference technique, and lay a foundation for further studies on the function of surviving.

All-trans retinoic acid (ATRA) has been shown to inhibit the growth of many malignancies by altering gap junctional intercellular communication (GJIC) and the expression of connexin (Cx) 43. Here, we report that the alteration of GJIC by ATRA may directly enhance the bystander effect (BE) of suicide gene therapy against prostate cancer in vitro and in vivo.PC-3 cells were exposed to different concentrations of ATRA for varying lengths of time in culture. Flow cytometry was performed to measure Cx43-positive cells and the GJIC function of the cells was examined with the scrape-loading dye transfer assay. Cells were treated with ATRA in combination with an adenovirus/ganciclovir (Ad-TK/GCV) system encoding herpes simplex virus-thymidine kinase, and the BE was assessed in the treatment of androgen-independent prostate cancer both in vitro and in vivo. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were performed to assess the expression of Cx43 mRNA and protein in tumor tissues.ATRA significantly increased the amount of Cx43-positive cells in a time- and dose-dependent manner (P0.05). GJIC functions were enhanced 3- to 5-fold in the presence of ATRA, although ATRA did not augment GCV toxicity of PC-3 cells. In the mixing assay, ATRA significantly increased cell killing when the ratio of TK-positive cells in the coculture ranged from 30% to 60% compared with ATRA-untreated cell (P0.05), and attained 50% cell killing cells when the ratio of TK-positive cell was 30%, but the same result did not appear until the ratio of TK-positive cell was up to 60% in the ATRA-untreated cell. Mice treated with a combination of ATRA and GCV had significantly smaller Ad-TK infected tumors than those treated with GCV or ATRA alone after 3-weeks of therapy (P0.05). However, from the fourth-week of therapy, there was no difference in tumor growth inhibition between GCV treatment and GCV + ATRA treatment (P0.05), as two tumors in the latter group started to grow more quickly than tumors in the control group. This phenomenon was not found in other groups.ATRA could enhance the efficiency of cell killing in suicide gene therapy against prostate cancer by strengthening the BE in vitro and in vivo. Induction of Cxs and GJIC by ATRA might provide an element of selectivity to suicide gene therapy. Future studies should focus on safety and tailoring this cooperative therapy to the patient.

The recurrence rate of superficial bladder cancer is still high even the patients received postoperative intravesical infusion of chemotherapeutic drugs, such as mitomycin C (MMC). Some studies showed that intravesical infusion of small interfering RNA (siRNA) could suppress the growth of bladder cancer in nude mice. This study was to establish an orthotopic animal model bearing human bladder cancer, monitor tumor progression by magnetic resonance imaging (MRI), and observe the synergistic effect of survivin short hairpin RNA (shRNA) in combination with MMC for intravesical treatment using this animal model.Human bladder cancer cell line T24 was inoculated into the bladders of 25 BALB/c nude mice to establish orthotopic bladder cancer model. MRI was performed to monitor tumor progression, using Gd-DTPA as contrast agent. The pathologic morphology of the bladders was observed. Eighteen mice bearing bladder cancer were randomized into 3 groups: untreated group, MMC group, and combination group. The bladders were weighed after 6 intravesical infusions.All the 25 mice developed bladder cancer after T24 cell inoculation. On MRI, no change in the bladders was observed at 7 days after inoculation, filling defect in the bladders, accordant to actual tumor size, was detected at 14, 21, and 28 days after inoculation. Pathologic examination showed that tumors grew in mucosa of the bladders at 7 days after inoculation, infiltrated into muscle layer at 14-28 days after inoculation, and invaded serosa at 35 days after inoculation. The inhibition rate of tumor growth was significantly higher in combination group than in MMC group (56.34% vs. 33.45%, P0.05).We successfully established an orthotopic bladder cancer model, which could simulate the progression of human bladder cancer approximately. MRI is a reliable way for dynamic detection of murine orthotopic bladder tumor. Down-regulating survivin expression by RNA interference could enhance the antitumor effect of MMC.

Objective To address whether hypercalciuria can stimulate calcium oxalate (CaOx) crystal deposition in kidney through osteopontin (OPN). Materials and Methods Rat tubular epithelial NRK cells were exposed to calcium. The cell viability, the cellular malondialdehyde content as a marker of reactive oxygen species (ROS), and the release of lactate dehydrogenase as markers of injury were detected. The production and gene expression of OPN were also examined. CaOx crystal attachment to cells was accomplished by measuring the calcium concentration of the cell lysates with atomic absorption analysis. Results Exposure to calcium produced signs of cell injury and ROS-induced lipid peroxidation. The messenger ribonucleic acid expression and production of OPN increased significantly. OPN knockdown can significantly decrease the amount of CaOx crystal attachment to NRK cells. Conclusion In response to exposure to high concentration of calcium, renal tubular epithelial NRK cells increase the production of OPN, which may have a promoting role in CaOx crystal adhesion to NRK cells by calcium stimulation.