Clinical outcomes and risk factors for mortality in recipients with carbapenem-resistant gram-negative bacilli infections after kidney transplantation treated with ceftazidime-avibactam: a retrospective study.

Background: Ceftazidime-avibactam is a treatment option for carbapenem-resistant gram-negative bacilli (CR-GNB) infections. However, the risk factors associated with ceftazidime-avibactam (CAZ-AVI) treatment failure in kidney transplant (KT) recipients and the need for CAZ-AVI-based combination therapy remain unclear. Methods: From June 2019 to December 2023, a retrospective observational study of KT recipients with CR-GNB infection treated with CAZ-AVI was conducted, with the primary outcome being 30-day mortality and secondary outcomes being clinical cure, microbiological cure, and safety. Risk factors for 30-day mortality and clinical failure were also investigated. Results: A total of 81 KT recipients treated with CAZ-AVI were included in this study. Forty recipients (49.4%) received CAZ-AVI monotherapy, with a 30-day mortality of 22.2%. The clinical cure and microbiological cure rates of CAZ/AVI therapy were 72.8% and 66.7%, respectively. CAZ-AVI alone or in combination with other medications had no effect on clinical cure or 30-day mortality. Multivariate logistic regression analysis revealed that a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (odds ratio [OR]: 4.517; 95% confidence interval [CI]: 1.397-14.607; P = 0.012) was an independent risk factor for 30-day mortality. Clinical cure was positively associated with the administration of CAZ-AVI within 48 hours of infection onset (OR: 11.009; 95% CI: 1.344-90.197; P=0.025) and negatively associated with higher APACHE II scores (OR: 0.700; 95% CI: 0.555-0.882; P=0.002). Four (4.9%) recipients experienced recurrence within 90 days after the initial infection, 3 (3.7%) recipients experienced CAZ-AVI-related adverse events, and no CAZ-AVI resistance was identified. Conclusion: CAZ-AVI is an effective medication for treating CR-GNB infections following kidney transplantation, even as monotherapy. Optimization of CAZ/AVI therapy (used within 48 hours of infection onset) is positively associated with potential clinical benefit. Further larger-scale studies are needed to validate these findings.

[Retracted] MicroRNA­539 inhibits the proliferation and invasion of bladder cancer cells by regulating IGF­1R.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell invasion assay data shown in Fig. 2C on p. 4921 were strikingly similar to data that had already been submitted for publication in different form in another article written by different authors at a different research institute. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a  reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 4917­4924, 2018; DOI: 10.3892/mmr.2018.8497].

Effect of preservation fluid contamination and associated possible donor-derived infections on early postoperative prognosis in kidney transplant recipients.

BACKGROUND: The study aims to analyze the epidemiology of preservation fluid (PF) contamination and investigate the impact of PF contamination and possible donor-derived infections(p-DDI) on early postoperative prognosis in kidney transplant (KT) recipients. METHODS: A total of 256 PF samples were collected for microbiological evaluation from all KT recipients who received deceased donor donations in our hospital from June 2018 to August 2022. Data on the baseline and clinical characteristics of these PF corresponding to recipients and donors were extracted from the electronic medical record. It mainly included the early postoperative complications and prognosis of KT recipients. RESULTS: From June 2018 to August 2022, 597 kidney transplants were performed in our center, with 260 recipients receiving kidney transplantation from donation after citizens' death. A total of 256 samples of PF were collected, of which 64.5% (165/256) were culture positive, and 24.6% (63/165) of the culture-positive PF were polymicrobial contamination. A total of 238 strains were isolated, of which coagulase-negative staphylococci (CoNS) had the highest proportion of 34.0% (81/238), followed by Klebsiella pneumoniae with 20.6% (49/238) and Escherichia coli with 8.8% (21/238). Recipients with culture-positive PF had a significantly higher incidence of postoperative infection (55.8% vs. 20.9%, P < 0.001) and DGF (38.2% vs. 24.2%, P = 0.023). In addition, the incidence of p-DDI was 12.9% (33/256). CRKP was the most common pathogen causing p-DDI. The recipients who developed p-DDI had a higher rate of graft loss (9.1% vs. 0.4%, P < 0.001), mortality (12.1% vs. 3.1%, P = 0.018), and longer postoperative hospital stay (30 days (19.5-73.5) vs. (22 days (18-32), P < 0.05) compared with recipients who did not develop p-DDI. CONCLUSIONS: Culture-positive PF is potentially significant for KT recipients, and p-DDI may increase the risk of poor prognosis for recipients. Prophylactic anti-infective treatment should be actively performed for highly virulent or multidrug-resistant (MDR) pathogens (especially Carbapenem-resistant Klebsiella pneumoniae, CRKP) in PF to avoid the occurrence of p-DDI.

Dual deficiency of melatonin and dihydrotestosterone promotes stromal cell damage and mediates prostatitis via the cGAS-STING pathway in sleep-deprived mice.

PURPOSE: Prostatitis is a highly prevalent condition that seriously affects men's physical and mental health. Although epidemiological investigations have provided evidence of a correlation between insufficient sleep and prostatitis, the pathogenesis of prostatitis remains unclear. We sought to identify the underlying mechanism involved and identify a promising therapeutic target. METHODS: Sleep deprivation (SD) was utilized to establish a mouse model of insufficient sleep in a special device. Prostatitis was observed at different time points post-SD. The degree of prostatitis was evaluated by pathological section and behavioural tests. Using immunofluorescence, western blot, and proteomic analyses, the underlying mechanism of SD-related prostatitis was investigated, and the development and therapeutic target of prostatitis were elucidated. RESULTS: SD, as an initial pathological trigger, resulted in a reduction in dihydrotestosterone and melatonin levels. Proteomic analysis revealed that the cGAS-STING pathway may play a significant role in inducing prostatitis. The subsequent results illustrated that the dual reduction in dihydrotestosterone and melatonin led to an accumulation of reactive oxygen species and the release of mitochondrial DNA (mt-DNA). The accumulation of mt-DNA activated the cGAS-STING pathway, which recruited inflammatory cells into the prostatic stroma through the secretion of interferon-ß. Consequently, an inflammatory microenvironment was formed, ultimately promoting the development of prostatitis. Notably, mice with SD-induced prostatitis gradually recovered to a normal state within 7 days of recovery sleep. However, after being subjected to SD again, these mice tended to have a more pronounced manifestation of prostatitis within a shorter timeframe, which suggested that prostatitis is prone to relapse. CONCLUSIONS: The cGAS-STING pathway activated by dual deficiency of dihydrotestosterone and melatonin plays a comprehensive inflammatory role in SD-related prostatitis. This research provides valuable insights into the pathogenesis, therapeutic targets, and prevention strategies of prostatitis.

Is There a Two-Way Risk between Decreased Testosterone Levels and the Progression and Prognosis of Chronic Kidney Disease? A Cohort Study Based on the National Health and Nutrition Examination Survey Database.

PURPOSE: The causal relationship between the incidence and prognosis of chronic kidney disease (CKD) and serum testosterone levels in patients is not yet fully understood. This study aims to use the National Health and Nutrition Examination Survey (NHANES), a large-scale nationally representative sample, to investigate the relationship between CKD and testosterone. MATERIALS AND METHODS: This study included six NHANES cycles for linear regression analysis, verified by multiple imputation methods. Stratified analysis and subgroup analysis were used to demonstrate the stability of CKD's effect on testosterone. Furthermore, we used Kaplan-Meier plots and log-rank tests to evaluate differences in survival rates between CKD male patients with low and normal levels of testosterone. RESULTS: From a total of 71,163 subjects, the cohort selected 28,663 eligible participants. Results showed that CKD patients had testosterone levels 28.423 ng/mL (24.762, 32.083) lower than non-CKD patients. The results of multiple imputations (ß=27.700, 95% confidence interval: 23.427, 31.974) were consistent with those of linear regression analysis, and the numerical match was good. Stratified regression analysis, and subgroup analysis results showed that CKD had a significant impact on testosterone at different dimensions. Kaplan-Meier plots showed significantly reduced survival rates in low testosterone CKD male patients (p<0.0001). CONCLUSIONS: The results of this big data analysis suggest that there may be a two-way risk between low levels of testosterone and CKD. The testosterone levels of CKD patients were significantly lower than those of the non-CKD population, and CKD patients with low testosterone levels had poorer prognoses. These results suggest that correcting testosterone levels in a timely manner can have preventive and therapeutic effects on the progression of CKD.

Safety and effectiveness of tigecycline combination therapy in renal transplant patients with infection due to carbapenem-resistant gram-negative bacteria.

Background: Carbapenem-resistant gram-negative bacterial (CRGNB) infections are increasing among kidney transplant recipients, and effective therapeutic options are limited. This study aimed to investigate the efficacy and adverse events associated with combination therapy tigecycline in renal transplant patients with CRGNB infections. Methods: This study retrospectively analyzed 40 Chinese patients with confirmed or suspected CRGNB infections who received tigecycline therapy. The patients' case features and clinical and microbiological data were analyzed. Results: A total of 40 renal transplant recipients received tigecycline therapy for a median duration of 9 (range, 3-25) days. CRGNB isolates were obtained from the organ preservation solution of the donor kidney in 28 patients, with confirmed transmission in 4 patients. Infections were detected in the bloodstream, urinary tract, sputum, and wound. The most prevalent isolates were Klebsiella pneumoniae (75%, 30/40), Acinetobacter baumannii (15%, 6/40), and Escherichia coli (10%, 4/40). A clinical response was observed in 32 (80%) patients. The 28-day all-cause mortality rate was 7.5% (3/40), while the one-year all-cause mortality rate was 2.5% (1/40). While one patient died owing to severe pancreatitis, no serious adverse events related to tigecycline therapy were reported. However, multiple indices of liver function and pancreatitis precursors increased after treatment with tigecycline compared to before treatment. Conclusion: Tigecycline therapy appears to be well tolerated in renal transplant recipients with multidrug-resistant bacterial infections. Nevertheless, attention should be paid to adverse reactions related to tigecycline therapy, especially gastrointestinal reactions, and the related laboratory tests should be closely monitored.

Development and external validation of a nomogram for predicting renal function based on preoperative data from in-hospital patients with simple renal cysts.

OBJECTIVE: To develop and validate a nomogram for predicting renal dysfunction in patients with simple renal cysts (SRCs). METHODS: We performed a multivariable logistic regression analysis of an in-hospital retrospective cohort of patients with SRCs in the Urology Department of the First Affiliated Hospital of Anhui Medical University. For prognostic model development, 386 patients with SRCs were enrolled from January 2016 to December 2018. External validation was performed in 46 patients with SRCs from January 2019 to April 2019. The primary outcome was renal dysfunction. RESULTS: Patients were divided into normal or abnormal estimated glomerular filtration rate groups (293 vs. 93) based on the cut-off value of 90 mL/minute/1.73 m2. Logistical regression analysis determined that age, haemoglobin, globulin, and creatinine might be associated with renal dysfunction, and a novel nomogram was established. Calibration curves showed that the true prediction rate was 77.42%, and decision curve analysis revealed that the nomogram was more effective with threshold probabilities ranging from 0.1 to 0.8. The area under the curves were 0.829, 0.752, and 0.888 in the overall training, internal, and external validation cohorts, respectively. CONCLUSIONS: We established a nomogram to predict the probability of developing renal dysfunction in patients with SRCs.

Effects of preservative fluid associated possible donor-derived carbapenem-resistant Klebsiella Pneumoniae infection on kidney transplantation recipients.

BACKGROUND: Infections remain a major cause of morbidity and mortality in kidney transplant (KT) recipients. This study aimed to investigate the preservation fluid (PF) samples from deceased donors and report the impacts of possible donor-derived carbapenem-resistant Klebsiella pneumoniae (pdd-CRKP) infections on KT recipients. METHODS: A retrospective study was performed that included all recipients who received kidney transplantation from deceased donors in our hospital between December 2018 and December 2020. A total of 212 patients received kidney transplantation from deceased donors, a total of 206 PF samples were collected, and 20 recipients had a CRKP-positive culture. Both donors and recipients with CRKP-positive PF cultures were divided into two groups, and continuous variables between the two groups were compared using independent-sample t tests and Mann-Whitney tests. Categorical variables were compared using the chi-square test or Fisher's exact test. The significance level of p values was set at 0.05. RESULTS: A total of 337 recipients underwent kidney transplantation, including 212 recipients of organs from deceased donors and 110 corresponding deceased donors. A total of 206 PF samples were collected, and 20 recipients had CRKP-positive PF cultures. The donors' length of ICU stay was a potential risk factor for CRKP positivity in the PF culture (P < 0.05). Fifteen recipients were infected with pdd-CRKP, and the incidence of pdd-CRKP infection was 7.3% (15/206). The use of antibiotics, including ceftazidime-avibactam (CAZ-AVI), was a potential protective factor against death and graft loss in recipients with a CRKP-positive PF culture (P < 0.05). CONCLUSIONS: This study shows that the incidence of pdd-CRKP is high in our centre, recipients with pdd-CRKP infection can still achieve a good prognosis with the use of antimicrobial agents including CAZ-AVI.

A Statistical Prediction Model for Survival After Kidney Transplantation from Deceased Donors.

BACKGROUND In an environment of limited kidney donation resources, patient recovery and survival after kidney transplantation (KT) are highly important. We used pre-operative data of kidney recipients to build a statistical model for predicting survivability after kidney transplantation. MATERIAL AND METHODS A dataset was constructed from a pool of patients who received a first KT in our hospital. For allogeneic transplantation, all donated kidneys were collected from deceased donors. Logistic regression analysis was used to change continuous variables into dichotomous ones through the creation of appropriate cut-off values. A regression model based on the least absolute shrinkage and selection operator (LASSO) algorithm was used for dimensionality reduction, feature selection, and survivability prediction. We used receiver operating characteristic (ROC) analysis, calibration, and decision curve analysis (DCA) to evaluate the performance and clinical impact of the proposed model. Finally, a 10-fold cross-validation scheme was implemented to verify the model robustness. RESULTS We identified 22 potential variables from which 30 features were selected as survivability predictors. The model established based on the LASSO regression algorithm had shown discrimination with an area under curve (AUC) value of 0.690 (95% confidence interval: 0.557-0.823) and good calibration result. DCA demonstrated clinical applicability of the prognostic model when the intervention progressed to the possibility threshold of 2%. An average AUC value of 0.691 was obtained on the validation data. CONCLUSIONS Our results suggest that the proposed model can predict the mortality risk for patients after kidney transplants and could help kidney specialists choose kidney recipients with better prognosis.

Efficacy of Ceftazidime-Avibactam in the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infection After Kidney Transplantation.

PURPOSE: The clinical efficacy of ceftazidime-avibactam (CAZ-AVI) in treating carbapenem-resistant Klebsiella pneumoniae (CRKP)-infected recipients after kidney transplantation (KT) has not been well evaluated. We aimed to assess its efficacy in a single-center cohort of KT recipients infected with CRKP. MATERIALS AND METHODS: We retrospectively observed KT recipients diagnosed with CRKP infection from June 2019 to July 2021. The primary outcome was 30-day mortality and secondary outcomes were 14-day clinical cure and 14-day microbiological cure. Logistic regression analysis was used to evaluate the relationship between CAZ-AVI treatment and prognosis. RESULTS: A total of 54 CRKP-infected KT recipients were recorded in this study. Twenty-two recipients received CAZ-AVI and 32 received other antibiotic regimens. Recipients in both groups had similar baseline characteristics, with the most common site of infection being surgical site infections (n=27; 50.0%) and bloodstream infections (n=23; 42.6%). Recipients treated with CAZ-AVI had significantly lower 30-day mortality (3/22 vs 14/32, P=0.019), significantly higher 14-day clinical cure (18/22 vs 17/32, P=0.030) and 14-day microbiological cure (19/22 vs 15/32, P=0.003) compared with recipients receiving other treatment regimens. Kaplan-Meier survival curves for 30-day mortality confirmed the findings (log-rank=0.014). In a multivariate logistic regression model, receiving CAZ-AVI was found to be an independent protective factor for 30-day mortality (odds ratio=0.148, 95% confidence interval, 0.027-0.800; P=0.026). No significant side effects were recorded. CONCLUSION: CAZ-AVI may be more valuable than other antibiotic regimens for the treatment of CRKP infection after kidney transplantation, and further large randomized controlled trials are needed to assess its efficacy.

Development and Validation of Nomogram for Predicting Delayed Graft Function After Kidney Transplantation of Deceased Donor.

BACKGROUND: Delayed graft function (DGF) is a major complication of kidney transplantation (KT), especially in patients receiving donor of decease (DD) KT. Therefore, the kidney donor pool is rare worldwide, it is critical to evaluate the risk coefficient of DGF using preoperative data of donors and recipients and provide a reference for clinical decision-making and resource allocation. METHOD AND ANALYSIS: A total of 238 DD recipients were performed in our center. Finally, 211 patients were included. The clinical database was divided into 34 clinical blood indicators (CBIs) and 6 demographics indexes (DIs). CBIs and DIs were screened for variables with P<0.05 and demonstrated the best cut-off value using multivariable logistics regression. The selected CBIs were passed through the least absolute shrinkage and selection operator (LASSO) to obtain the predictive factors and synthesized into a Riskscore, forming a nomogram with the selected DIs. We used receiver operating characteristic (ROC), calibration, and decision curve analysis (DCA) to verify the discrimination and clinical effects of this nomogram. Finally, 10-fold cross-validation was conducted internally to show the effect of the model. RESULTS: The 34 CBIs of the database finally screened out 12 predictors, which were synthesized into Riskscore. The 6 DIs selected 3 variables. Riskscore and 3 DIswere constructed into a nomogram, and the ROC of the nomogram has an AUC value of 0.725. Calibration and DCA showed excellent verification effects on the nomogram. The 10-fold crossover internal validation also demonstrated the model's excellent discrepancy. CONCLUSION: The nomogram has an excellent ability to predict DGF and provides an essential reference for decision-making and resource allocation in a clinical setting.

Analysis of Risk Factors for Carbapenem-Resistant Klebsiella pneumoniae Infection and Its Effect on the Outcome of Early Infection After Kidney Transplantation.

Background: Infections remain a major cause of morbidity and mortality in kidney transplant (KT) recipients. This study was performed to identify the overall prevalence of early infections, prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection after KT, one-year postoperative mortality in patients with early infections and risk factors for CRKP infections. Methods: We conducted a retrospective study of all patients who received KT in our hospital between January 2017 and December 2019. We evaluated the demographic, clinical, infection characteristics and the one-year postoperative outcomes. Results: Among the 419 patients who received KT between January 2017 and December 2019, 150 patients had at least one infection within 90 days after KT. The total prevalence of early infections was 36.1% (150/415), the prevalence of early CRKP infections was 10.4% (43/415), and the one-year postoperative mortality was 15.3% (23/150) in patients with early infections. The risk factors independently related to one-year postoperative mortality were mechanical ventilation (MV) > 48 h (Odds ratio (OR)= 13.879, 95%Confidence interval (CI): 2.265~85.035; P=0.004) and CRKP infection (OR=6.751, 95% CI: 1.051~43.369; P =0.044). MV> 48 h was independently related to CRKP infection (OR=3.719, 95% CI: 1.024~13.504; P=0.046). Kaplan-Meier survival curves showed that the one-year survival rate of patients infected with CRKP in the early postoperative stage was significantly lower than that of uninfected patients. Conclusions: In general, the prevalence of early infections after KT is high, and CRKP infection is closely correlated with poor prognosis. The effective prevention and treatment of CRKP infection is an important way to improve the one-year survival rate after KT.

Meta-Analysis for Social Support Degree of Kidney Transplant Recipients: Evidence from China.

Social support refers to the subjective and (or) objective influence of various social relationships on individuals, which has a certain influence on the negative emotions of the kidney transplant patients. But there are still significant differences among various studies, so we performed a meta-analysis to analyze the social support degree of kidney transplant recipients. This article searched and selected the relevant cross-sectional surveys from PubMed, Embase, VIP, CNKI, Wanfang, and CBM databases according to the inclusion and exclusion criteria and used the STROBE list combined with the observational research quality evaluation tools of Sanderson to conduct the quality appraisal. The "meta" and "metaphor" packages of the R software version 3.5.1 were used for the meta-analysis. A total of 17 studies with 2697 patients were included. The total scores of the social support and objective support of the renal transplant patients were abundant after the operation, indicating that the economic, physical, and emotional supports from the family, society, and the official organization are accepted. But the subjective support and support utilization degree were general. The support utilization was different among different genders, and female patients were lower than the males. In particular, the female patients relatively presented autism and the social support utilization degree was low. Medical staffs are needed to join the family, hospital, and society to create favorable conditions and improve the social support system and the utilization degree of the social support, thereby promoting the physical and mental health development of the patients.

Genetic polymorphisms in metabolic enzymes and transporters have no impact on mycophenolic acid pharmacokinetics in adult kidney transplant patients co-treated with tacrolimus: A population analysis.

WHAT IS KNOWN AND OBJECTIVE: Mycophenolate mofetil, an ester prodrug of mycophenolic acid (MPA), is widely used to prevent graft rejection after kidney transplantation. The pharmacokinetic (PK) of MPA has been extensively studied, which revealed a high degree of variability. An integrated population PK (PopPK) model of MPA and its main metabolite mycophenolic acid glucuronide (MPAG) was developed using the adult patients who underwent kidney transplant and were administered oral mycophenolate mofetil combined with tacrolimus. METHODS: In total, 917 MPA and 740 MPAG concentrations in191 adult patients were analysed via nonlinear mixed-effects modelling. The concentration-time data were adequately described using a chain compartment model, including central and peripheral compartments for MPA and a central compartment for MPAG. Stepwise forward inclusion and backward elimination procedures were used to investigate the effects of genetic polymorphisms, including in UGT1A8, UGT1A9, UGT2B7, ABCB1, ABCC2, ABCG2, SLCO1B1, SLCO1B3, and HNF1α. RESULTS AND DISCUSSION: These genetic polymorphisms in metabolic enzymes and transporters have no obvious impact on the PK of MPA in adult patients who underwent kidney transplant and were co-treated with tacrolimus. The post-transplant time, serum albumin, and creatinine clearance were identified as significant covariates affecting the PK of MPA and MPAG, which should be considered in the clinical use of mycophenolate mofetil. WHAT IS NEW AND CONCLUSION: We established a PopPK model of MPA and MPAG in Chinese adult patients who underwent kidney transplant and were co-treated with tacrolimus. Genetic polymorphisms in metabolic enzymes and transporters showed no obvious impact on MMF PK. A model-informed dosing strategy was proposed by the established model, and MMF dose adjustment should be based on ALB levels and the post-transplantation time.

Kidney transplantation improve semen quality in patients with dialysis: A systematic review and meta-analysis.

Kidney transplantation has been considered as the most effective therapy for patients with end-stage renal disease. However, less attention was attached to infertility. The present meta-analysis was conducted to compare the semen quality between patients with dialysis and patients after kidney transplantation. An extensive search in MEDLINE, PubMed and Web of Science was conducted from inception to March 2021. The data extracted for meta-analysis included sample size and characteristics, main reported outcomes like semen quality and hormone levels. For the semen quality and hormone levels, the standardized mean difference (SMD) and 95% confidential interval (CI) were calculated to evaluate the effect size. Finally, 5 studies were included in meta-analysis. Kidney transplantation could improve the sperm density of patients undergoing dialysis (SMD 1.58 [0.02, 3.15]). Additionally, the sperm motility was also improved after the kidney transplantation (SMD 3.26 [0.73, 5.79]). The sperm density of kidney transplantation patients was lower than that in healthy subjects (SMD -0.75 [-1.42, -0.07]), same as the sperm motility (SMD -0.50 [-0.80, -0.20]). Our meta-analysis suggests kidney transplantation could improve semen quality of patients with ESRD, including sperm density and sperm motility. Of note, semen quality of renal transplantation recipient still is inferior to healthy subjects.

NLRC5 mediates cell proliferation, migration, and invasion by regulating the Wnt/ß-catenin signalling pathway in clear cell renal cell carcinoma.

NLRC5, a newly discovered member of the NLR family, has been reported to regulate immune responses and promote cell proliferation, migration, and invasion in hepatocellular carcinoma. However, to date, the potential regulatory roles and molecular mechanisms by which NLRC5 affects the development and progression of clear cell renal cell carcinoma (ccRCC) remain largely unknown. In this study, human clinical data from The Cancer Genome Atlas database revealed that increased NLRC5 expression was associated with advanced stage and poor prognosis in ccRCC patients. Moreover, experimental results showed that NLRC5 is aberrantly overexpressed in human ccRCC tissues and cell lines. Depletion of NLRC5 attenuated ccRCC cell proliferation, migration, and invasion and suppressed ccRCC growth in a nude mouse model. By contrast, overexpression of NLRC5 promoted the proliferation, migration, and invasion of ccRCC cells in vitro. Additionally, NLRC5 expression is not only positively correlated with ß-catenin but also coordinates the activation of the downstream Wnt/ß-catenin signalling pathway. Together, our data suggest that NLRC5 may be a potential therapeutic target for ccRCC therapy.

MicroRNA­539 inhibits the proliferation and invasion of bladder cancer cells by regulating IGF­1R.

Bladder cancer is the most frequent malignancy of the urinary tract and the seventh most common cancer worldwide. The abnormal expression of microRNAs has been frequently observed in various types of human cancers, including bladder cancer. In addition, an increasing body of evidence has demonstrated that microRNAs are potential targets for cancer diagnosis, treatments and prognosis. The aim of the present study was to investigate the expression patterns and potential roles of microRNA­539 (miR­539) in bladder cancer and its underlying mechanism. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was performed to detect miR­539 expression in the bladder cancer tissues and cell lines. Following transfection, MTT and cell invasion assays were used to investigate the effects of miR­539 overexpression or IGF1R underexpression on bladder cancer cell proliferation and invasion. Bioinformatics analysis, a luciferase reporter assay, RT­qPCR and western blot analysis were utilized to determine the potential targets of miR­539 in bladder cancer. The results revealed that miR­539 levels were relatively decreased in bladder cancer tissues and cell lines when compared with those observed in the matched adjacent normal bladder tissues and normal bladder epithelial cell line. miR­539 expression was associated with the tumor stage and lymph node metastasis of patients with bladder cancer. In addition, the expression of miR­539 suppressed bladder cancer cell proliferation and invasion. Insulin like growth factor 1 receptor (IGF­1R) was identified as a direct target of miR­539, and miR­539 was also observed to regulate the protein kinase B and extracellular signal­regulated kinases signaling pathways. IGF­1R was markedly upregulated in bladder cancer tissues and negatively associated with miR­539 expression levels. Furthermore, IGF­1R knockdown in bladder cancer cells significantly inhibited cell proliferation and invasion. To the best of our knowledge, these results demonstrated for the first time that miR­539 may act as a tumor suppressor and serve important roles in tumorigenesis and progression of bladder cancer. Thus, miR­539/IGF­1R may be a potential therapeutic target for the treatment of bladder cancer.

Prevalence of Prostatitis-Like Symptoms and Outcomes of NIH-CPSI in Outpatients with Lifelong and Acquired PE: Based on a Large Cross-Sectional Study in China.

Premature ejaculation (PE) is one of the most common sexual dysfunctions, which were associated with prostatitis-like symptoms (PLS). We intended to explore the prevalence of prostatitis-like symptoms and outcomes of National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) scores in outpatients with lifelong (LPE) and acquired premature ejaculation (APE). From December 2013 to December 2015, a total of 498 consecutive heterosexual men with PE and 322 male healthy subjects without PE were enrolled. Each of them completed a detailed questionnaire on demographics information, sexual and medical histories, and the NIH-CPSI. Assessment of NIH-CPSI and definition of PLS and PE were used to measure the PLS and NIH-CPSI scores and ejaculatory function for all subjects. Finally, a total of 820 subjects (including 498 men in PE group and 322 men in control group) were enrolled in our study. The mean ages were significantly different between PE and no PE groups. Men with PE reported worse PLS and higher NIH-CPSI scores (P < 0.001 for all). Similar findings were also observed between men with LPE and APE. Men with APE also reported higher rates of PLS and scores of NIH-CPSI (P < 0.001 for all). Multivariate analysis showed that PLS and NIH-CPSI scores were significantly associated with PE.