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Organophosphate esters (OPEs) impact health in many ways. Since its relationship with urinary incontinence remains unknown, we aimed to explore their associations in the US general population. We combined the results of urine specimens test and self-reported urinary incontinence conditions from the National Health and Nutrition Examination Survey (NHANES) 2013–2014 among 2666 participants and then conducted linear regression and logistic regression to analyse associations between log2-transformed OPE concentrations and urinary incontinence. We found that 0.92% of men and 15.74% of women complained of mixed urinary incontinence (MUI). The concentrations of diphenyl phosphate (DPHP) were significantly correlated to MUI among women when treated as a continuous variable (adjusted odds ratio (OR) = 1.15; 95% confidence interval (CI), 1.01–1.31; p = 0.0369) and as a categorical variable (adjusted OR = 1.24; 95% CI, 1.03–1.49; p for trend = 0.0245), whereas no positive correlation was found in males. There were no significant associations between the other three OPEs: bis(2-chloroethyl) phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and dibutyl phosphate (DBUP). The association of DPHP with an increased prevalence OR of MUI in women is a public health concern; future prospective studies are needed to explore its potential mechanism. Supplementary Information The online version contains supplementary material available at 10.1007/s11356-021-14153-5.

Objective: To evaluate the oncological outcomes of ductal adenocarcinoma of the prostate (DAC) managed with radical prostatectomy (RP) or radiotherapy (RT) and optimize the proper treatment modality to DAC comprehensively. Methods: The cohorts included a total of 528 patients from the Surveillance, Epidemiology and End Results (SEER) database, 354 receiving RP and 174 receiving RT. Cox proportional hazards regressions were performed to assess cancer specific mortality (CSM) and overall mortality (OM) between treatment groups. A competing risk analysis was further conducted. Subgroup analyses by age and level of prostate-specific antigen (PSA) were performed. Propensity score matching was implemented. Results: Patients managed with RP had lower risks of CSM and OM compared with RT (before matching: Hazard ratio [HR]=0.24, 95% confidence interval [CI] 0.13–0.47 and HR=0.26, 95% CI 0.17–0.40, respectively; after matching: HR=0.18, 95% CI 0.04–0.82 and HR=0.28, 95% CI 0.11–0.70, accordingly). Subgroup analyses demonstrated that patients in the middle tertile of the age or with lower tertile PSA level managed with RP took lower risks of OM significantly (HR=0.18, 95% CI 0.06–0.57, p

The purpose of this study was to evaluate the association between dietary inflammatory index (DII) and urinary incontinence (UI) among a representative sample of the US women. We performed a cross-sectional analysis of women younger than 65 years using the 1999 to 2016 NHANES (National Health and Nutrition Examination Survey) populations. DII were calculated based on baseline dietary intake using 24-h dietary recalls. UI was determined and categorized by self-reported questions. Multivariable logistic regression models were used to assess the association between DII and UI. Stratified linear regression models were applied to test for interaction in prespecified subgroup of interest. A total of 13,441 women age between 20 and 65 years were included in the final analysis. Of these participants 3230 (24.03%) complained of urgency UI, 5276 (39.25%) complained of stress UI and 2028 (15.09%) complained of mixed UI. On multivariate analysis, analysis with DII categorized as quartiles revealed significantly increase odds of urgency UI in the most pro-inflammatory quartile compared to the most anti-inflammatory quartile (OR 1.24, 95% CI 1.07–1.44, P = 0.004 for trend) in full adjustment model. Similar results were observed in SUI (OR 1.14, 95% CI 1.00–1.30, P = 0.021 for trend) and MUI (OR 1.20, 95% CI 1.02−1.43, P = 0.022 for trend). More pro-inflammatory diets, as presented by higher DII scores are associated with an increased likelihood of UI in American women younger than 65 years. Further studies are needed to explore the possible physiological mechanism and evaluate the potential therapeutic implications.

Objective:We evaluate the association between the Dietary Inflammatory Index (DII) and kidney stones.Design:We performed a cross-sectional analysis using data from National Health and Nutrition Examination Survey (NHANES). Dietary intake information was assessed using first 24-h dietary recall interviews, and the Kidney Conditions were presented by a questionnaire. The primary outcome was to investigate the association between DII and incidence of kidney stones, and the secondary outcome was to assess the association between DII and nephrolithiasis recurrence.Setting:The NHANES, 2007–2016.Participants:The study included 25 984 NHANES participants, whose data on DII and kidney stones were available, of whom 2439 reported a history of kidney stones.Results:For the primary outcome, after fully multivariate adjustment, DII score is positively associated with the risk of kidney stones (OR = 1·07; 95 % CI 1·04, 1·10). Then, compared Q4 with Q1, a significant 38 % increased likelihood of nephrolithiasis was observed. (OR = 1·38; 95 % CI 1·19, 1·60). For the secondary outcome, the multivariate regression analysis showed that DII score is positively correlated with nephrolithiasis recurrence (OR = 1·07; 95 % CI 1·00, 1·15). The results noted that higher DII scores (Q3 and Q4) are positively associated with a significant 48 % and 61 % increased risk of nephrolithiasis recurrence compared with the reference after fully multivariate adjustment (OR = 1·48; 95 % CI 1·07, 2·05; OR = 1·61; 95 % CI 1·12, 2·31).Conclusions:Our findings revealed that increased intake of pro-inflammatory diet, as a higher DII score, is correlated with increased odds of kidney stones incidence and recurrence.

Inflammation is crucial in the pathogenesis of lower urinary tract symptoms (LUTS) in men. Diet modulates inflammation. Therefore, diet could be a modifiable factor in male LUTS prevention and treatment. We aimed to investigate the association between dietary inflammatory potential and male LUTS. We used two cycles of National Health and Nutrition Examination Survey (NHANES) with self-report LUTS data. We calculated the dietary inflammatory index (DII) based on a 24 h diet recall and evaluated male LUTS. Clinical LUTS was defined as two or more coexisting symptoms. We used univariate and multivariate logistic regression models, the smooth curve fitting to analyze the relationship between clinical LUTS and the DII score. Subgroup analyses were conducted. We observed a positive non-linear relationship between clinical LUTS and DII. We found that when DII was higher than the inflection point 2.39, a 1-unit increase in DII was associated with 26.1% higher adjusted odds of clinical LUTS. Subgroup analyses showed that the DII score was only positively correlated with clinical LUTS risk in non-drinkers, smokers, and non-obese people (DII >2.39). Inflammation might be the key mechanism bridging dietary consumption to male LUTS. Excessive pro-inflammatory food intake (DII >2.39) warrants special vigilance, especially for non-drinkers, smokers, and non-obese men.

Objective: Studies have showed that different follow-up starting points might potentially impact the comparison between primary (PMIBC) and secondary muscle-invasive bladder cancer (SMIBC), but the only previous meta-analysis did not differentiate the follow-up starting points of included studies. With more trials published, we aim to update the meta-analysis comparing PMIBC and SMIBC. Methods: PubMed, Embase, Cochrane Library and ClinicalTrial.gov. systematically searched. Literatures comparing the survival outcomes of PMIBC and SMIBC were selected. Outcomes of cancer-specific mortality (CSM), overall mortality (OM) and recurrence-free survival (RFS) were pooled and grouped based on the starting point of follow-up (after initial diagnosis or radical cystectomy (RC)). Newcastle-Ottawa Scale (NOS) and funnel plot were employed to assess the study quality and publication bias, respectively. Results: A total of 17 high-quality studies were selected, with 5558 patients aged from 59.8 to 72.7 (mean value) involved. The male-to-female ratio was roughly 4:1 (4390/1124). SMIBC had lower risk of CSM after initial diagnosis (HR 0.81, 95%CI 0.67-0.98, P=0.03, I2=70%), but higher risk of CSM after RC (HR 1.45, 95%CI 1.27-1.65, P

This study used National Health and Nutrition Examination Surveys data from 1999 to 2006 to investigate the association between dietary inflammatory potential, represented by dietary inflammatory index (DII) scores, and the risk of sarcopenia in U.S. adults. A total of 25,781 participants were included in the study. The DII scores were calculated based on dietary information collected from 24-hour recalls. Men and women were classified as sarcopenic if appendicular lean mass (ALM) adjusted for BMI (ALMBMI) was

Background Patients with metastatic prostate cancer (mPCa) have a very low 5-year survival rate. How to choose proper treatment of mPCa remains controversial. Method Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015), we performed analyses of cancer-specific mortality (CSM) and overall mortality (OM) in the comparisons of local treatment (LT) versus no local treatment (NLT) and radical prostatectomy (RP) versus radiation therapy (RT). To balance the characteristics between 2 treatment groups, propensity score matching was performed. Considering the selection bias, we additionally used an instrument variate (IVA) to calculate the unmeasured confounders. Result Multivariate regression showed that patients receiving LT had the lower risks of OM and CSM after adjustment of covariates (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.35-0.44 and HR 0.39, 95% CI 0.34-0.45). In the IVA-adjusted model, LT showed more survival benefits compared with NLT, with HR of 0.57 (95% CI 0.50-0.65) and cancer-specific HR of 0.59 (95% CI 0.51-0.68), respectively. For those receiving LT, adjusted multivariate regression indicated that RP is superior to RT (HR 0.60; 95% CI 0.43-0.83 for OM and HR 0.61; 95% CI 0.42-0.91 for CSM). The IVA-adjusted model also showed that RP presented with potentially better survival outcome compared with RT, although the effect was not statistically significant (HR 0.63; 95% CI 0.26-1.54 for OM and HR 0.47; 95% CI 0.16-1.35 for CSM). Conclusion Among patients with metastatic prostate cancer, LT might bring better survival benefits in decreasing CSM and all-cause mortality compared with NLT. For those receiving LT, RP showed better survival outcomes than RT.

Immunotherapy has been a milestone for muscle-invasive bladder cancer (MIBC), but only a small portion of patients can benefit from it. Therefore, it is crucial to develop a robust individualized immune-related signature of MIBC to identify patients potentially benefiting from immunotherapy. The current study identified patients from the Cancer Genome Atlas (TCGA) and immune genes from the ImmPort database, and used improved data analytical methods to build up a 45 immune-related gene pair signature, which could classify patients into high-risk and low-risk groups. The signature was then independently validated by a Gene Expression Omnibus (GEO) dataset and IMvigor210 data. The subsequent analysis confirmed the worse survival outcomes of the high-risk group in both training (p < 0.001) and validation cohorts (p = 0.018). A signature-based risk score was proven to be an independent risk factor of overall survival (p < 0.001) and could predict superior clinical net benefit compared to other clinical factors. The CIBERSORT algorithm revealed the low-risk group had increased CD8+ T cells plus memory-activated CD4+ T-cell infiltration. The low-risk group also had higher expression of PDCD1 (PD-1), CD40, and CD27, and lower expression of CD276 (B7-H3) and PDCD1LG2 (PD-L2). Importantly, IMvigor210 data indicated that the low-risk group had higher percentage of “inflamed” phenotype plus less “desert” phenotype, and the survival outcomes were significantly better for low-risk patients after immunotherapy (p = 0.014). In conclusion, we proposed a novel and promising prognostic immune-related gene pair (IRGP) signature of MIBC, which could provide us a panoramic view of the tumor immune microenvironment of MIBC and independently identify MIBC patients who might benefit from immunotherapy.

Introduction: We aimed to develop an easy-to-use individual survival prognostication tool based on competing risk analyses to predict the risk of 5-year cancer-specific death after radical prostatectomy for patients with prostate cancer (PCa).Methods: We obtained the data from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2016). The main variables obtained included age at diagnosis, marital status, race, pathological extension, regional lymphonode status, prostate specific antigen level, pathological Gleason Score. In order to reveal the independent prognostic factors. The cumulative incidence function was used as the univariable competing risk analyses and The Fine and Gray's proportional subdistribution hazard approach was used as the multivariable competing risk analyses. With these factors, a nomogram and risk stratification based on the nomogram was established. Concordance index (C-index) and calibration curves were used for validation.Results: A total of 95,812 patients were included and divided into training cohort (n = 67,072) and validation cohort (n = 28,740). Seven independent prognostic factors including age, race, marital status, pathological extension, regional lymphonode status, PSA level, and pathological GS were used to construct the nomogram. In the training cohort, the C-index was 0.828 (%95CI, 0.812–0.844), and the C-index was 0.838 (%95CI, 0.813–0.863) in the validation cohort. The results of the cumulative incidence function showed that the discrimination of risk stratification based on nomogram is better than that of the risk stratification system based on D'Amico risk stratification.Conclusions: We successfully developed the first competing risk nomogram to predict the risk of cancer-specific death after surgery for patients with PCa. It has the potential to help clinicians improve post-operative management of patients.

Background: Urolithiasis is the most common complication of horseshoe kidney (HK), which can be treated by extracorporeal shock wave lithotripsy (ESWL), flexible ureteroscopy (FURS), and percutaneous nephrolithotomy (PCNL). When comparing treatments of ESWL and FURS, it is unclear which is more efficient and safe. The objective of this study was to compare the efficacy and safety of FURS and SWL for the treatment of urolithiasis in HK patients.Methods: A systematic search of the Web of Science, PubMed, and EMBASE was performed in February 2021. Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias in each study.Results: Five studies published between 2008 and 2018 were synthesized in the present meta-analysis. The study revealed that FURS compared with SWL had greater initial and overall stone-free rates (SFRs). Risk ratios (RRs) were 2.46 (P < 0.00001) in initial SFRs, 1.36 (P = 0.02) in overall SFRs. No differences were found in the retreatment ratio, RRs were 0.49 (P = 0.43). In addition, no major complications were encountered, and all the complications were mild to moderate.Conclusion: The study demonstrated that FURS and SWL are effective and safe treatments for patients with HK with stones (

Objective: The aim of this study is to investigate the associations between phthalate exposure and UI in a nationally representative sample of US adults.Methods: Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) database was used for analysis. In total, 2,818 participants with measurements for phthalate metabolites and complete UI questionnaire data were enrolled in our study. Further, seven phthalate metabolites were measured, which were obtained from urine samples and creatinine-standardized in the subsequent analyses. After divided these phthalate metabolites into three groups, multivariable regression models were performed to evaluate the association between phthalate metabolites and UI rates. Moreover, interaction analyses and subgroup analyses stratified by gender were performed.Results: In these seven phthalate metabolites, high level of mono-carboxynonyl phthalate (MCNP), mono-carboxyoctyl phthalate (MCOP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP) and mono-3-carboxypropyl phthalate (MCPP) showed increased risk of UI [odds ratio (OR) = 1.52, 1.42, 1.43, 1.50, 1.51, respectively, all p value < 0.05]. Trend test showed that incidence of UI increased significantly with concentration. A higher incidence of UI among participants was observed in the maximal tertile of phthalate when comparing with the lowest tertile. Subgroup analysis found that different phthalates have varying influence for different types of UI. Moreover, the analyses stratified for sex indicated that the high concentrations of MCNP and median concentrations of MCCP were associated with increase of the odds of UI in women and in men, respectively.Conclusion: Overall, the exposure to phthalates was positively associated with UI among US adults. Notably, different phthalates have varying influence for different types of UI, and male and female exposure to phthalate could result in the different prevalence of UI.

Membrane vesicles, including exosomes and microparticles (MPs), serve to package and transfer the cellular cargo during inter/extracellular communication, which is of great interest in cancer development, especially in the dissemination of signal transduction-associated traits from donor cells to recipient cells. Although increasing evidence suggests that microparticles (MPs) contribute to the development of cancer, their unique characteristics remain to be exploited. Here, we examined the secretion of MPs in tumor tissues from triple-negative breast cancer (TNBC) patients and found that the tumor cells could release MPs loaded with immune checkpoint molecular programmed cell death ligand 1 (PD-L1), especially in patients treated with traditional clinical interventions, such as chemotherapy and radiotherapy. These PD-L1-loading MPs contribute to the suppressive immune microenvironment, eventually resulting in the tumor progression in TNBC. Mechanically, we proved that PD-L1-loading MPs could suppress the activation and function of functional cluster of differentiation CD8+ T cells. Meanwhile, the PD-L1-loading MPs could mediate the differentiation of macrophages toward the immune-suppressive M2 phenotype via the activation of the TANK-binding kinase 1 (TBK1)/signal transducer and activator of transcription 6 (STAT6) signal and suppression of the serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signal. Given the increasing MP production induced by traditional clinical interventions, we further combined chemotherapy with the PD-L1 inhibitor atezolizumab (ATZ) to efficiently abrogate the immunosuppression caused by the PD-L1-loading MPs. Therefore, our study unveils the mechanism by which tumor cells systemically evade immune surveillance by releasing the PD-L1-loading MPs, and provides new insights into clinical TNBC immunotherapy.

Background: Previous meta-analysis evaluated a limited number of parameters regarding the comparison of BTPV and TURP for BPH. Method: PubMed, Embase and Cochrane Library were searched for literature comparing BTPV with TURP. Data of efficacy (IPSS, Qmax, PVR and QoL) and safety were extracted and evaluated using either SMD or OR with 95% CI. All analyses were performed by RevMan 5.3. Results: Eleven trials with 1690 patients were selected. Compare to BTPV, TURP had better 6-month IPSS (SMD=0.36, 95% CI 0.08 to 0.63), better 1- (SMD=-0.38, 95% CI -0.63 to -0.12), 6- (SMD=-0.73, 95% CI -0.99 to -0.46) and 12-month Qmax (SMD=-0.47, 95% CI -0.85 to -0.10), better 6-month PVR (SMD=1.18, 95% CI 0.87 to 1.48), as well as better 3- (SMD=-0.24, 95% CI -0.48 to -0.01) and 6-month QoL (SMD=-0.62, 95% CI -0.91 to -0.33). However, BTPV had shorter catheterization time (SMD=-0.96, 95% CI -1.12 to -0.79) and hospital stay (SMD=-0.71, 95% CI -0.89 to -0.53), less hemoglobin decrease (SMD=-1.09, 95% CI -1.27 to -0.91) and virtually shorter operation time (SMD=-0.15, 95% CI -0.31 to 0.01). Moreover, BTPV had fewer occurrence of overall complications (OR=0.52, 95% CI 0.40 to 0.69), Clavien III-IV complications (OR=0.61, 95% CI 0.37 to 1.02), blood transfusion (OR=0.25, 95% CI 0.09 to 0.69), hematuria (OR=0.27, 95% CI 0.13 to 0.56) and capsular perforation (OR=0.19, 95% CI 0.08 to 0.48). Subgroup analysis indicated BTPV and bipolar TURP had similar total complications (OR 1.08, 95% CI 0.40-2.88, P=0.88) and Clavien III-IV complications (OR 1.42, 95% CI 0.36-5.57, P=0.61) and blood transfusion rate (OR 0.28, 95% CI 0.04-1.73, P=0.17). Conclusion: Both TURP and BTPV could significantly improve IPPS, Qmax, PVR and QoL. TURP had slightly better short-term efficacy, while BTPV had better safety. However, subgroup analysis found bipolar TURP and BTPV had similar safety.

Previous studies have revealed lymph node density (LND) to be an independent prognostic factor in cancer. However, data from 20 years ago failed to demonstrate the prognostic value of LND in node-positive renal-cell carcinoma (RCC). This study was undertaken to comprehensively investigate the prognostic value of LND in node-positive RCC.Within the Surveillance, Epidemiology and End Results database, we accessed data on patients diagnosed with histologically confirmed node-positive RCC from 2004 to 2014. The cubic spline smoothing technique and Cox regression were used to evaluate the correlation between LND and cancer-specific mortality (CSM). The X-Tile program was used to identify the optimal cut point of LND in node-positive RCC. Robustness of the results in various subgroups was also explored. Univariable and multivariable analyses were performed to determine predictors of CSM. Sensitivity analyses were performed.A total of 1750 node-positive RCCs were identified. We found a nonlinear positive correlation between the likelihood of CSM and LND. X-Tile analysis identified best cut point of LND as 35% with a maximum chi-square of 18.58. Every 10% increase in LND increased CSM by 5% (hazard ratio = 1.05; 95% confidence interval, 1.02-1.07; P .0001), and LND ≥ 35% was associated with 41% increase in CSM (hazard ratio = 1.41; 95% confidence interval, 1.20-1.65; P .0001) in fully adjusted Cox regression. Results of sensitivity analyses were consistent with those of the primary analysis.LND is an independent prognostic factor in node-positive RCC and should be incorporated into the cancer staging system.

Purpose To evaluate the association between tertiary Gleason pattern 5 (TGP5) and biochemical recurrence (BCR) in patients with prostate cancer (PCa) with a Gleason score (GS) of 7 after radical prostatectomy (RP). Patients and methods This retrospective study identified 350 patients who received RP and were graded as GS 7 (3+4 or 4+3) at the West China Hospital from January 2009 to December 2017. Initially, the patients were divided into two groups, TGP5 absence and TGP5 presence, independent of Gleason score. We further stratified the patients by adding the Gleason score into four groups: GS 3+4, GS 3+4/TGP5, GS 4+3, and GS 4+3/TGP5. Cox proportional-hazards models were used to evaluate the association between the status of TGP5 and BCR after adjusting for the confounding factors. Results The risk of BCR was significantly higher in patients with TGP5 when compared to patients without TGP5 (P=0.04, HR=2.17 95%, Cl: 1.03-4.59). For patients with primary Gleason pattern 4, the risk of BCR for patients with Gleason 4+3/TGP5 was statistically significantly higher than Gleason 4+3 (P=0.04, HR=2.45, 95% Cl: 1.04-5.76). Conclusion The TGP5 in patients with GS 7 had strong association with the risk of BCR and was an independent predictor for BCR. Further research on larger data sets is needed to confirm these findings.

Objective: Administration of drugs targeting anti-cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) is often associated with serious immune-related adverse events (irAEs). Here, we performed a comprehensive analysis of organ-specific irAEs and treatment-related hematologic abnormalities and musculoskeletal disorders resulting from anti-CTLA-4 treatment. Materials and methods: PubMed, the Cochrane library, Web of Science, and ClinicalTrials.gov were searched for studies between January 1990 and March 2018 reporting AEs associated with anti-CTLA-4 therapies. Results: A total of 11 clinical trials with 7,088 patients were included; of these, data were accessible for 10 on ClinicalTrials.gov. Compared with control therapies (placebo, chemotherapy, radiation therapy, or vaccine), anti-CTLA-4 therapies (ipilimumab and tremelimumab) were associated with an increased risk of serious irAEs, predominantly dermatologic (rash: odds ratio [OR] 3.39, P

Background Lipid profiles are believed to play an important role in the tumorigenesis and progression of prostate cancer (PCa), but research combining those data is lacking. Therefore, this meta-analysis aims to assess the prognostic role of lipid profiles after RP. Method We systematically searched PubMed, Embase, and Cochrane Library Central Register of Controlled Trials for articles evaluating association between lipid profiles and prognosis after RP. Odds ratio (OR) and hazard ratio (HR) of lipid profiles for advanced pathological tumor features and biochemical recurrence (BCR) were extracted and pooled OR and HR were calculated. Newcastle-Ottawa scale was used for study quality assessment and funnel plot was used for evaluating publication bias. Results Twelve articles involving 11,108 patients were eventually selected. We found low HDL was associated with more frequent occurrence of pathological T stage (pT) ≥ T3 (pooled OR = 1.29, 95% CI 1.07–1.56) and Gleason score (GS) ≥8 (pooled OR = 1.32, 95% CI 1.02–1.72) after RP. Hypertriglyceridemia was also linked with higher risk of pT ≥ T3 (pooled OR = 1.20, 95% CI 1.01–1.42) and positive surgical margin (PSM) (pooled OR = 1.36, 95% CI 1.11–1.65). However, no significant association was observed between BCR and abnormal lipid profile levels. Conclusion Low HDL level was associated with more common occurrence of pT ≥ T3 and GS ≥8, and elevated triglycerides level was linked higher risk of pT ≥ T3 and PSM, but none of the lipid subfractions was correlated with biochemical recurrence after RP. Electronic supplementary material The online version of this article (10.1186/s12944-019-1068-6) contains supplementary material, which is available to authorized users.

Background For localized prostate cancer (PCa), radical prostatectomy (RP) and radiotherapy (RT) are two standard interventions to decrease PCa mortality. Contemporary studies contained the elderly people; analyses focusing on patients over 75 years of age were still lacking. Method In the Surveillance Epidemiology and End Results (SEER) database (2004‐2015), people over 75 years of age with cT2 stage were selected in our research. Multivariable Cox proportional hazard models were used to analyze cancer‐specific mortality (CSM) and overall mortality (OM) after adjustment. The propensity score matching was performed to assume the randomization. An instrument variate (IVA) was used to calculate the unmeasured confounders. Results Radical prostatectomy is superior to RT in OM and CSM after adjustment for covariates (HR = 0.54, 95% CI = 0.47‐0.62, P

Previous study compared limited number of parameters post the treatment of cold knife and laser urethrotomy for urethral stricture and controversy about the superiority of those two techniques still remains. This study aims to update the evidence and provide better clinical guidance. We systematically searched Pubmed, Embase, ClinicalTrial.gov, and Cochrane Library Central Register of Controlled Trials for articles comparing cold knife and laser urethrotomy for urethral stricture. Parameters including maximum urinary flow (Qmax), recurrence, reoperation, complications, operation time, and Visual Analog Scale (VAS) pain score were compared using RevMan 5.3. Seven articles involving 453 patients were eventually included. The cold-knife group had better 6-month Qmax (MD – 0.95, 95% CI – 1.49 to – 0.41) and similar 3-month and 12-month Qmax compared with the laser group. No significance was observed regarding the comparison of recurrence rate. The laser group had lower risk of bleeding (OR 0.08, 95% CI 0.01–0.43), lower rate of reoperation (OR 0.39, 95% CI 0.19–0.81) and longer operation time (MD 4.09, 95% CI 3.35–4.82). There was no significant difference in terms of other complications and VAS pain score. Cold knife and laser urethrotomy had similar efficacy regarding short-term and long-term recurrence rate and Qmax, except that the cold-knife group had slightly better 6-month Qmax. However, the laser group had less risk of bleeding and lower rate of reoperation but also longer operation time.

This study investigated the association between Dietary Inflammatory Index and sex hormones in a large, nationally representative adult male sample.We utilized data from the 2013-2014 and 2015-2016 National Health and Nutrition Examination Survey. Males aged ≥20 years who provided a 24-hour dietary intake history and underwent serum sex hormone testing were included in analysis. Weighted proportions and multivariable analysis controlling for age, race, energy, smoking status, education level, body mass index and time of venipuncture were used to evaluate the associations between Dietary Inflammatory Index and sex hormones.For 4,151 participants, Dietary Inflammatory Index ranged from -5.05 to 5.48. Mean±SD total testosterone was 419.30±176.27 ng/dl. Mean±SD total testosterone was lower among men in the highest tertile compared with men in the lowest tertile group (410.42±171.97 vs 422.71±175.69, p0.001). A per unit increase in Dietary Inflammatory Index was related to 4.0% (95% CI 0.5-7.6) higher odds of testosterone deficiency. In the fully adjusted multivariable model, males in Dietary Inflammatory Index tertile 3 (the most pro-inflammatory) had 29.6% (3.1-63.0) higher odds of testosterone deficiency than those in tertile 1 (p trend=0.025). Interaction tests revealed no significant effect of body mass index on the association of Dietary Inflammatory Index with testosterone deficiency and all sex hormone parameters.Men adhering to a more pro-inflammatory diet appear to have a higher risk of testosterone deficiency, indicating the important role of diet in male reproductive health.

Background Controversy remains despite several studies have discussed the role of bariatric surgery in improving male’s sexual function. This study aims to evaluate the efficacy of bariatric surgery in promoting male’s erectile function. Methods PubMed, EMbase, The Cochrane Library, CNKI and Clinical Trails.gov were searched from database inception to May 2019. The language of publication was limited in English. The International Index of Erectile Function (IIEF) score and Brief Male Sexual Function Inventory (BSFI) score were set as the primary outcome. Results Eleven studies with a total of 370 patients were enrolled in this meta-analysis. The results showed significant improvement in the IIEF score (erectile function: MD = 5.33, 95% CI 4.12–6.54; intercourse satisfaction: MD = 2.57, 95% CI 1.19–3.94; orgasmic function: MD = 0.50, 95%CI 0.60–0.94; overall satisfaction: MD = 1.67, 95% CI 0.78–2.56; sexual desire: MD = 1.27, 95% CI 0.61–1.93; total erectile function: MD = 7.21, 95% CI 4.33–10.10) and the BSFI score (erection: MD =2.53, 95% CI 2.39–2.67; ejaculation: MD = 1.40, 95% CI 1.28–1.51; desire: MD =1.40, 95% CI 1.32–1.49; problem assessment: MD = 2.20, 95% CI 2.06–2.34; sexual satisfaction: MD = 0.70, 95% CI 0.60–0.76) in obese individuals after bariatric surgery. Conclusions This systematic review and meta-analysis indicated that bariatric surgery could be effective in promoting males’s sexual function for obese individuals.

There is a significant heterogeneity in the immunotherapeutic responsiveness of each muscle-invasive bladder cancer (MIBC) patient. In our research, we aimed to identify a novel classification of MIBC based on immunogenomic profiling that may facilitate the reasonable stratification of prognosis and response to immunotherapy. The single-sample gene-set enrichment analysis (ssGSEA) was used to analyze the RNA-seq data of 29 important immune signatures from TCGA. Unsupervised hierarchical clustering was performed to identify an immunogenomic classification of MIBC. Then, we assessed the features of the classification in prognosis, immune infiltration, tumor-infiltration lymphocytes, HLA genes, and PD-L1 expression level. A total of 399 MIBC samples were included and three subtypes named Immunity_High, Immunity_Medium, and Immunity_Low were identified. The Immunity_High had a significant advantage in overall survival over the Immunity_Medium and Immunity_Low (p = 0.046 and p = 0.024). From Immunity_Low to Immunity_High, immune cell infiltration and stromal content showed an upward trend (p < 0.001). Meanwhile, Immunity_High was associated with a significantly higher proportion of TILs including dendritic cells resting, macrophages M1, mast cells resting, T cells CD4 memory activated, and T cells CD8+. And the expression levels of all HLA genes and PD-L1 of Immunity_High were the highest, consistent (p < 0.001). Two hundred ninety eight MIBC patients treated with immunotherapy from the IMvigor210 were included to form an independent validation cohort to verify the robustness of immunogenomic classification and the ability to predict the response to immunotherapy. This classification had potential clinical implications for predicting prognosis and immunotherapeutic responsiveness of MIBC patients.

At present, focal laser ablation (FLA) as a new PCa local treatment has attracted attention. We aim at comparing the survival outcomes between radiotherapy (RT) and FLA to reveal whether FLA can be used as an alternative to RT for patients with low and intermediate-risk localized PCa.We conducted analyses with data from the SEER database (2004–2015). Propensity score matching and instrumental variate (IV) were used to reduce the influence of bias and unmeasured confounders maximally.In the adjusted multivariate regression, FLA had lower overall survival (OS) benefits (HR = 1.49; 95%CI: 1.18–1.87; p

Background: Papillary renal carcinoma (PRCC) is one of the important subtypes of kidney cancer, with a high degree of heterogeneity. At present, there is still a lack of robust and accurate biomarkers for the diagnosis, prognosis and treatment selection of PRCC. Considering the important role of tumor immunity in PRCC, we aim to construct a signature based on immune-related gene pairs (IRGPs) to estimate the prognostic of patients with PRCC.Methods: We obtained gene expression profiling and clinical information of patients with PRCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), which were divided into discovery and validation cohorts, respectively. The immune-related genes in the samples were used to construct gene pairs, and the immune-related genes pairs (IRGPs) with robust impact for overall survival (OS) were screened out to construct the signature by univariate analysis, multivariate Cox analysis, and least absolute shrinkage and selection operator (Lasso) analysis. Then we verified the prognostic role of the signature, and assessed the relationship between this signature with tumor immune infiltration and functional pathways.Results: A total of 315 patients were included in our study, and divided to discovery (n=287) and validation (n=28) cohorts. Finally, we selected 14 IRGPs with a panel of 22 unique genes to construct the prognostic signature. According to the signature, we stratified patients into high-risk group and low-risk group. In both discovery and validation cohorts, the results of Kaplan-Meier analysis showed that there were significant differences in OS between the two groups (p+ T cells, Tregs, and T follicular cell helper were significantly higher in the high-risk group. Functional analysis showed that multiple immune-related signaling pathways were enriched in the high-risk group.Conclusions: We successfully established an individualized prognostic immune-related gene pairs signature, which can accurately and independently predict the OS of patients with PRCC.

In zones of violent conflict in the tropics, social disruption leads to elevated child mortality, of which malaria is the leading cause. Understanding the social determinants of malaria transmission may be helpful to optimize malaria control efforts. We conducted a cross-sectional study of healthy children aged 2 months to 5 years attending well-child and/or immunization visits in the Democratic Republic of Congo (DRC). Six hundred and forty-seven children were tested for malaria antigenemia by rapid diagnostic test and the accompanying parent or legal guardian simultaneously completed a survey questionnaire related to demographics, socioeconomic status, maternal education, as well as bednet use and recent febrile illness. We examined the associations between variables using multivariable logistic regression analysis, chi-squared statistic, Fisher’s exact test, and Spearman’s rank correlation, as appropriate. One hundred and twenty-three out of the 647 (19%) children in the study tested positive for malaria. Higher levels of maternal education were associated with a lower risk of malaria in their children. The prevalence of malaria in children of mothers with no education, primary school, and beyond primary was 41/138 (30%), 41/241 (17%), and 39/262 (15%), respectively (p = 0.001). In a multivariable logistic regression model adjusting for the effect of a child’s age and study site, the following remained significant predictors of malaria antigenemia: maternal education, number of children under five per household, and HIV serostatus. Higher maternal education, through several putative causal pathways, was associated with lower malaria prevalence among children in the DRC. Our findings suggest that maternal education might be an effective ‘social vaccine’ against malaria in the DRC and globally.

Supplemental Digital Content is available in the text, Background: Previous evidence directly evaluating the efficacy and safety of abiraterone and enzalutamide treatment for castration-resistant prostate cancer (CRPC) is limited. We aim to include more randomized controlled trials (RCTs) to comprehensively assess the efficacy and safety of abiraterone and enzalutamide treatment. Methods: PubMed, Embase, and ClinicalTrial.gov were systematically searched. Pooled hazard ratios (HRs) were calculated using Stata 12.0 software. The comparison of the prostate-specific antigen (PSA) response rate and adverse events (AEs) between the treatment and control groups were performed using RevMan 5.3 software. Results: Eight eligible RCTs with 6,490 patients were selected. Pooled HRs were 0.72 for overall survival, 0.45 for radiographic progression-free survival (rPFS), and 0.36 for PSA PFS. abiraterone and enzalutamide could significantly increase the PSA response rate OR = 8.67, 95%CI 4.42–17.04) and any AE occurrence (OR = 1.98, 95%CI 1.46–2.68). The treatment group had more occurrence of fatigue (OR = 1.34, 95%CI 1.20–1.49), back pain (OR = 1.15, 95%CI 1.01–1.15), hot flush (OR = 1.76, 95%CI 1.50–2.06), diarrhea (OR=1.22, 95%CI 1.07–2.40) and arthralgia (OR = 1.34, 95%CI 1.16–1.54). Particularly, AEs of special interest including any grade hypertension (OR = 2.06, 95%CI 1.71–2.47), hypokalemia (OR = 1.80, 95%CI 1.42–2.30) and fluid retention or edema (OR = 1.38, 95%CI 1.17–1.63) also occurred less in the control group. Moreover, a higher incidence of high-grade hypertension (OR = 2.60, 95%CI 1.79–3.79) and extremity pain (OR = 4.46, 95%CI 2.81–7.07) was observed in the treatment group. Conclusion: The survival benefits of abiraterone and enzalutamide for CRPC were evident and promising, while the risk of AE occurrence was also acceptably higher in the treatment group than in the placebo group.

Combining immune checkpoint inhibitors has shown its efficacy compared to monotherapy in advanced malignancies. We conducted this meta-analysis to provide latest evidence on the objective response rate (ORR) and incidence of treatment-related high-grade adverse events (AEs) during nivolumab and ipilimumab combination treatment and further explore from different drug dose level. PubMed and the 2019 American Society of Clinical Oncology (ASCO) annual meeting abstracts were searched for qualified clinical trials up to June 2019. Of the 23 clinical trials (13 from publications and 11 from ASCO abstracts) included, 2,114 and 2,674 patients were eligible for efficacy and safety analysis, respectively. Pooled analysis suggested that the overall ORR was achieved in 34.5% [95% confidence interval (CI), 29.1–40.4%] of patients. There was no significant difference between nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks (N3I1-Q3W) and nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (N1I3-Q3W) arms in ORR [30.8% vs 41%; odds ratio (OR), 0.72; 95% CI, 0.39–1.30; P = 0.275]. Grade 3–4 AEs related to combination therapy occurred in 39.9% (95% CI, 33.5–46.7%) of patients; the most commonly reported grade 3–4 treatment-related AEs were diarrhea (5.28%), colitis (3.96%) and increased alanine aminotransferase (3.51%). Incidence of grade 3–4 AEs were significant lower in N3I1-Q3W arm than in N1I3-Q3W arm (31.3% vs 55.9%; OR 0.52; 95% CI, 0.32–0.87; P = 0.012). Treatment-related death was rare and occurred in 2.0% (95% CI, 1.5–2.7%) of patients. Our comprehensive study provides more precise data on the incidence of treatment-related high-grade AEs and ORR among patients receiving nivolumab and ipilimumab combination regimens. Patients on the N3I1-Q3W arm had comparable ORR and significantly occurred less grade 3–4 AEs than patients on the N1I3-Q3W arm. Our finding is of great importance in assisting clinical trial design and clinical medication choice.

The high potential for cancer relapse has emerged as a crucial challenge of human bladder cancer treatment. To date, those stem-like bladder cancer cells (BCSCs) have been considered as seeds that induce frequent tumor recurrence. However, the cell origin of cancer stem cells (CSCs) is still a controversial issue, due in part to the findings that CSCs not only origin from normal stem cells but also converted from differentiated tumor cells. Here, we describe a biomaterial 3D collagen I gel culture system, where non-tumorigenic cells can obtain tumorigenic potential and revert back into CSCs through the integrin α2β1/PI3K/AKT/NF-κB cascade, resulting in the tumorigenesis in bladder tissues. Furthermore, inhibiting this integrin α2β1/PI3K/AKT/NF-κB signal pathways can significantly impair the tumorigenic capacity of CSCs. Simultaneously, in vivo studies demonstrate that IFN-γ secreted by T cells can trigger those CSCs into dormancy through the IDO/Kyn/AHR/P27 cascade, which elicit chemotherapy resistance and cancer relapse. To address the challenges of suppressing bladder tumor growth and preventing tumor reoccurrence, we use IDO and integrin α2β1 signal pathway inhibitors combine with chemotherapeutic agents to awaken dormant bladder CSCs and inhibit their tumorigenic ability as well as effectively eliminate CSCs. The therapeutic approaches we propose provide new insights for eradicating tumors and reducing bladder cancer relapse after therapy.

The continuous intake of antithrombotic drugs during holmium laser enucleation of the prostate (HoLEP) remains nonconsensual. We aim to pool those controversial evidence and provide practical guidance of oral antithrombotics on HoLEP for benign prostate hyperplasia (BPH). PubMed, Embase and CENTRAL database were systematically searched up to June 2019 for trials on patients with and without oral antithrombotics undergoing HoLEP. Number of events and mean value with standard deviation were, respectively, extracted for dichotomous and continuous parameters. Subgroup analyses of anticoagulation and antiplatelet were also performed. All statistical analyses were conducted with Review Manager v.5.3 software. Newcastle–Ottawa Scale (NOS) was used to assess the quality of selected trials. Nine studies with 5528 patients were eventually selected, and patients included were generally older than 65 years. It revealed that the non-antithrombotic group had a lower rate of blood transfusion (OR 0.21, 95% CI 0.10–0.45, P

Background: For localized prostate cancer (PCa) with a low disease burden, whole-gland resection seems like overtreatment, while focal therapy, including cryosurgery, can achieve similar outcomes. We aimed at comparing the long-term survival outcomes of cryotherapy and radical prostatectomy (RP) and further exploring whether RP can be replaced by cryosurgery for those with low-risk PCa. Methods: We conducted analyses from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015) and performed propensity score matching and used an instrumental variate to reduce the influence of bias and unmeasured confounders to the greatest extent. Results: In the multivariate regression, patients who received cryotherapy had higher risk of overall mortality (OM) (hazard ratio [HR] = 2.52, 95% confidence interval [CI] 1.99-3.20, p < 0.001), but no significant difference was observed in decreasing cancer-specific mortality (CSM) (HR = 1.38, 95% CI 0.63-3.03, p = 0.41) after adjusting the confounders. After propensity score matching, patients who underwent cryotherapy had higher OM and CSM rates (HR = 2.70 [95% CI 1.99-3.66, p < 0.001] and HR = 2.99 [95% CI 1.19-7.48, p = 0.02], respectively). In the IV-adjusted analyses, RP was superior to cryotherapy in decreasing OM (HR = 2.52, 95% CI 1.99-3.20), while no obvious decrease of CSM was observed in the comparison of RP and cryotherapy (HR = 1.38, 95% CI 0.63-3.03). The subgroup analyses showed that RP displayed an obvious benefit in decreasing CSM (HR = 5.02, 95% CI 1.30-19.39, p = 0.02) for those with a prostate-specific antigen (PSA) level higher than 10 ng/ml. Conclusion: RP ranked as the best treatment in regard to tumor control, but the advantages of cryotherapy became evident when taking functional and oncological outcomes into account, especially for low- and intermediate-risk PCa with low PSA levels.

Background: Previous evidence directly evaluating the efficacy and safety of the treatment for castration-resistant prostate cancer (CRPC) by androgen receptor (AR) signaling-axis inhibitors was limited by the quantity of randomized controlled trials (RCT) and biased by non-RCTs. We aim to comprehensively assess the efficacy and safety of abiraterone and enzalutamide using only RCTs. Patients and methods: We systematically searched Pubmed, Embase, MEDLINE and ClinicalTrial.gov for RCTs providing data of treatment outcomes by AR inhibitors (abiraterone and enzalutamide). Pooled hazard ratios (HR) with 95%CI for survival benefits were calculated using STATA 12.0. Comparison of prostate-specific antigen (PSA) response rate, aggregated adverse event (AE) statistics, any grade AE, high-grade AE (grade ≥3), AE of special interest between the treatment and control groups were performed by RevMan 5.3 and STATA 12.0. Results: Eight eligible RCTs with 6296 patients were selected. Pooled HR were 0.72 for overall survival, 0.45 for radiographic progression-free survival and 0.36 for PSA PFS. AR inhibitors could significantly increase the rate of PSA response (OR=8.67, 95%CI 4.42-17.04) and AE occurrence (OR=1.98, 95%CI 1.46-2.68). The treatment group had a higher occurrence of any-grade fatigue (OR=1.34, 95%CI 1.20-1.49), back pain (OR=1.15, 95%CI 1.01-1.15), hot flush (OR=1.76, 95%CI 1.50-2.06), diarrhea (OR=1.22, 95%CI 1.07-2.40) and arthralgia (OR=1.34, 95%CI 1.16-1.54). Particularly, the outcomes for AEs of special interest including any grade hypertension (OR=2.06, 95%CI 1.71-2.47), hypokalemia (OR=1.80, 95%CI 1.42-2.30) and fluid retention or edema (OR=1.38, 95%CI 1.17-1.63) also favored the control group. In terms of high-grade AEs, a higher occurrence of hypertension (OR=2.60, 95%CI 1.79-3.79) and pain in extremity (OR=4.46, 95%CI 2.81-7.07) was observed in the treatment group. There was no significant difference regarding other AEs analyzed in this study. Conclusion: The survival benefits by AR inhibitors for CRPC were evident and promising at the cost of acceptably higher risk of AEs occurrence.

Biochemical recurrence (BCR) is important for measuring the oncological outcomes of patients who undergo radical prostatectomy (RP). Whether transurethral resection of the prostate (TURP) has negative postoperative effects on oncological outcomes remains controversial. The primary aim of our retrospective study was to determine whether a history of TURP could affect the postoperative BCR rate. We retrospectively reviewed patients with prostate cancer (PCa) who had undergone RP between January 2009 and October 2017. Clinical data on age, prostate volume, serum prostate-specific antigen levels (PSA), biopsy Gleason score (GS), metastasis stage (TNM), D'Amico classification, and American Society of Anesthesiologists (ASA) classification were collected. Statistical analyses including Cox proportional hazard models and sensitivity analyses which included propensity score matching, were performed, and the inverse-probability-of-treatment-weighted estimator and standardized mortality ratio-weighted estimator were determined. We included 1083 patients, of which 118 had a history of TURP. Before matching, the non-TURP group differed from the TURP group with respect to GS (P = 0.047), prostate volume (mean: 45.19 vs 36.00 ml, P < 0.001), and PSA level (mean: 29.41 vs 15.11 ng ml−1, P = 0.001). After adjusting for age, PSA level, T stage, N stage, M stage, and GS, the TURP group showed higher risk of BCR (hazard ratio [HR]: 2.27, 95% confidence interval [CI]: 1.13–3.94, P = 0.004). After matching (ratio 1:4), patients who underwent TURP were still more likely to develop BCR according to the adjusted propensity score (HR: 2.00, 95% CI: 1.05–3.79, P = 0.034). Among patients with PCa, those with a history of TURP were more likely to develop BCR after RP.

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. The classic manifestation of IgAN is episodic hematuria and proteinuria. Nephrotic syndrome (NS) is not very common in IgAN, reported to occur in only 5–10% of IgAN patients. However, the clinical and pathological characteristics and long-term outcomes of patients with NS-IgAN at onset remain unknown. A retrospective study was conducted, enrolling 1165 patients with biopsy-proven IgAN from West China Hospital in 2008–2015. Patients with renal biopsy of minimal change disease with mesangial IgA deposits were excluded. The renal endpoint was defined as 50% decrease in eGFR or progressing into end-stage renal disease (ESRD). A total of 1165 patients were enrolled with average age of 34.58, and 171 (14.7%) patients were presented with NS. Comparing NS and non-NS groups, significance differences were shown in hypertension (HTN), 24-h urine protein, serum albumin, serum creatine, eGFR and uric acid. NS group had severe pathological changes such as endocapillary hypercellularity, tubular atrophy or interstitial fibrosis and crescent, but less segmental glomerulosclerosis or adhesion and global sclerosis. During the average follow-up of 44.27 months, 29.8% (51/171) NS patients and 15.8% (157/994) non-NS patients progressed to the renal endpoint. 5-year renal survival rates were 73.1% and 87.8% (P

Background Focal therapy for localized prostate cancer (PCa) remains investigational. We aimed to investigate the oncologic outcomes of focal laser ablation (FLA) and compare them with those of radical prostatectomy (RP). Patients and Methods Patients treated with FLA or RP for localized PCa between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier curves and multivariate Cox proportional hazard models were utilized to calculate the survival benefits. Propensity score (PS) matching and adjusted standardized mortality ratio weighting (SMRW) models were used to balance the 2 groups. Subgroup analyses according to tumor stage, prostate-specific antigen level, and Gleason score were also conducted. Results A total of 12,875 patients were included, of whom 12,433 were treated with RP, whereas 442 were treated with FLA; 321 pairs of patients were eventually matched. Baseline characteristics were well-balanced by PS matching. The mean follow-up was 59.62 months for the RP group and 62.26 months for the FLA group. Before matching, the FLA group had lower but statistically insignificant cancer-specific mortality (CSM) (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.15-2.45; P = .4879) and higher any-cause mortality (ACM) (HR, 2.35; 95% CI, 1.38-3.98; P = .0016) compared with the RP group, which was supported by the outcomes in the PS-matched cohort (CSM: HR, 0.82; 95% CI, 0.18-3.67; P = .7936; ACM: HR, 2.35; 95% CI, 1.38-3.98; P = .0016) and the SMRW model (CSM: HR, 0.61; 95% CI, 0.15-2.44; P = .4877; ACM: HR, 2.01; 95% CI, 1.18-3.42; P = .0103). Conclusion Our study suggests that FLA had a higher risk of ACM but an insignificantly lower risk of CSM compared with RP. More high-quality trials are needed to confirm and expand our findings.

The tumor microenvironment is associated with various tumor progressions, including cancer metastasis, immunosuppression, and tumor sustained growth. Tumor‐associated macrophages (TAMs) are considered an indispensable component of the tumor microenvironment, participating in the progression of tumor microenvironment remodeling and creating various compounds to regulate tumor activities. This study aims to observe enriched TAMs in tumor tissues during bladder cancer development, which markedly facilitated the proliferation of bladder cancer cells and promoted tumor growth in vivo. We determined that TAMs regulate tumor sustained growth by secreting type I collagen, which can activate the prosurvival integrin α2β1/PI3K/AKT signaling pathway. Furthermore, traditional chemotherapeutic drugs combined with integrin α2β1 inhibitor showed intensive anticancer effects, revealing an innovative approach in clinical bladder cancer treatment.

Xiaonan Zheng,1,* Shi Qiu,1,2,* Xinyang Liao,1 Xin Han,3 Kun Jin,1 Lu Yang,1 Qiang Wei1 1Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Center of Biomedical Big Data, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3West China Medical School, Sichuan University, Chengdu, Sichuan, People’s Republic of China *These authors contributed equally to this work Objective: To evaluate the association between metabolic syndrome (MetS) and the accumulation of its components with prostate cancer (PCa). Patients and methods: Patients undergoing radical prostatectomy were retrospectively included. Patients were grouped by low risk and intermediate-high risk according to International Society of Urological Pathology grade. Multivariable logistic regression and Cox hazard regression model were utilized to assess the association of MetS with overall survival, biochemical recurrence, upgrading, upstaging, and positive surgical margin (PSM) after prostatectomy. Besides, trend test was also performed to evaluate the impact of the accumulation of MetS components on postoperative pathological feature. Results: A total of 1,083 patients were eventually enrolled. With a median follow-up of 40.45 months, 197 patients were diagnosed with MetS. No significant association between MetS and survival outcomes and pathological features was found. However, we did notice that the accumulation of the MetS components could lead to an elevated gradient of the PSM risk in the entire cohort (one component: OR=1.46; two components: OR=1.89; ≥3 components: OR=2.07; P for trend=0.0194) and intermediate-high risk group (one component: OR=1.4; two components: OR=1.85; ≥3 components: OR=2.05; P for trend=0.0127). Conclusion: The accumulation of MetS components could lead to increasing risk of PSM on the entire PCa cohort and patients with intermediate-high risk PCa after prostatectomy, but not for the low-risk patients. Keywords: prostate cancer, PCa, metabolic syndrome, MetS, International Society of Urological Pathology, ISUP, positive surgical margin, PSM

Indoor positioning technique is the foundation of Internet of Things (IoT) and location big data, which provides IoT function and location data for retail, manufacturing, energy, medical, emergency, logistics, robotics and other industries. Indoor positioning performance is an important performance indicator of IoT intelligent communication terminals. In order to accurately evaluate the indoor positioning performance of IoT intelligent communication terminals, this paper constructs an indoor positioning performance test system for IoT intelligent communication terminals. The test results show that the uncertainty of horizontal positioning accuracy of Wi-Fi positioning and Bluetooth positioning can be limited within 0.32 m (k=2).

Currently, the standard management for locally advanced prostate cancer (PCa) is still controversial. In our study, we aimed to compare the survival outcomes of radical prostatectomy (RP) versus external beam radiotherapy (EBRT). We conducted analyses with a large cohort of 38,544 patients from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2016). Propensity score matching, Kaplan-Meier method, and Cox proportional hazard regression were used to reduce the influence of bias and compare the overall survival (OS) and cancer specific survival (CSS). Several different sensitivity analyses including inverse probability of treatment weighting and standardized mortality ratio weighting were used to verify the robustness of the results. Totally, 33,388 men received RP and 5,156 men received EBRT with cT3-4N0M0 PCa were included in this study. According to the Kaplan-Meier curves, RP performed better in both OS and CSS compared with EBRT (P

The necessity to cease anticoagulation before photoselective vaporization (PVP) surgery remains nonconsensual. We aimed at assessing the efficacy and safety of PVP among high-risk benign prostate hyperplasia (BPH) patients on or off anticoagulation. We systematically searched Pubmed, Embase, and Cochrane Library Central Register of Controlled Trials (CENTRAL). 2299 patients from 11 studies were eventually included. Newcastle–Ottawa Scale (NOS) was employed to assess the quality and risk of bias of each study. All statistical analyses were conducted with Review Manager v.5.3 software. Ten parameters (operation time, laser time, blood transfusion, urethral stricture, urinary tract infection, reoperation, dysuria, capsule perforation, catheterization time, and re-catheterization) from patients on or off anticoagulant therapy were collected. The patients without anticoagulants performed better at catheterization time [MD − 0.54, 95% CI (− 0.82, − 0.26), P = 0.96, I2 = 0] with a reduction of 0.54 day than those on anticoagulants. Significant statistical difference was not observed from other parameters. Subgroup analysis, grouped by the power output of PVP systems (80 W, 120 W and 180 W), consistently showed no statistical significant difference except at catheterization time in the 180-W PVP subgroup. PVP, a safe and effective option for high-risk BPH patients, work comparably regardless of anticoagulant therapy, despite non-anticoagulant patients have shorter catheterization time. It is implied that the use of anticoagulants might be unnecessary to stop for high-risk BPH patients undergoing PVP for the sake of safety, which certainly requires further investigations to confirm.

Background: For localized prostate cancer (PCa), radical prostatectomy (RP) and radiotherapy (RT) are two standard interventions to decrease PCa mortality. Contemporary studies contained the elderly people, analyses focusing on patients over 75 years old were still lacking. Method: In the Surveillance Epidemiology and End Results (SEER) database (2004-2015), old people over 75-year-old with cT2 stage were selected in our research. Multivariable Cox proportional hazard models were used to analyze cancer-specific mortality (CSM) and overall mortality (OM) after adjustment. The propensity score matching was performed to assume the randomization. An instrument variate (IVA) was used to calculate the unmeasured confounders. Results: It showed that RP is superior to RT in OM and CSM after adjustment for covariates (hazard ratio [HR] = 0.54, 95% CI = 0.47-0.62, p

Background Ketamine, a noncompetitive N-methyl-D-aspartate receptor antagonist, is widely used as an intravenous anesthetic agent and has also been shown to possess anti-inflammatory effects, but its effects on high-mobility group box-1(HMGB1) have not been well defined. In the present study, we investigated the effects of ketamine on HMGB1 in lipopolysaccharide (LPS)-induced Raw264.7 cells and in a mouse model of cecal ligation and puncture-induced sepsis. Materials and methods Raw264.7 cells were incubated with or without 1 μg/mL LPS in the presence or absence of ketamine, mitogen-activated protein kinases (MAPKs) inhibitor, or small interfering RNA (siRNA). The protein and expression levels of inflammatory mediators, such as HMGB1, nitric oxide (NO), and heme oxygenase-1(HO-1), were measured using enzyme-linked immunosorbent assays, Western blot analysis, and real-time polymerase chain reaction. The effect of ketamine on nuclear factor erythroid 2-related factor 2 (Nrf2) and MAPKs activation was evaluated using enzyme-linked immunosorbent assays and Western blot analysis. Results In vitro , ketamine inhibits HMGB1 and NO release and induces HO-1 expression in a concentration-dependent manner, whereas HO-1 siRNA antagonizes the inhibition of HMGB1 and NO. The effect of ketamine is inhibited by the p38 MAPK inhibitor SB203580 and Nrf2 siRNA, indicating that ketamine induces HO-1 via p38 MAPK and Nrf2. In vivo , ketamine increases survival and decreases serum and lung HMGB1 levels in cecal ligation and puncture-induced sepsis. Conclusions Ketamine inhibits LPS-induced HMGB1 release through HO-1 induction, and these effects may be mediated by blockade of p38 MAPK and Nrf2 signaling pathways.

Background: IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide and up to 40% will develop end-stage renal disease (ESRD) within 20 years. However, predicting which patients will progress to ESRD is difficult. The purpose of this study was to develop a predictive model which could accurately predict whether IgAN patients would progress to ESRD. Methods: Six machine learning algorithms were used to predict whether IgAN patients would progress to ESRD: logistic regression, random forest, support vector machine (SVM), decision tree, artificial neural network (ANN), k nearest neighbors (KNN). Nineteen demographic, clinical, pathologic and treatment parameters were used as input for the prediction models. Results: Random forest is best able to predict progression to ESRD. The model had accuracy of 93.97% and sensitivity and specificity of 80.60% and 95.27%, respectively. Conclusions: Machine learning algorithms can effectively predict which patients with IgA nephropathy will progress to end stage renal disease.

Metabolic syndrome (MetS) has been reported to be associated with adverse outcomes in cancer patients. However, the relationship between MetS and upper tract urothelial carcinoma (UTUC) has yet to be explored.To investigate the prognostic value of MetS in UTUC after radical nephroureterectomy.A total of 644 patients with UTUC after radical nephroureterectomy were identified at West China Hospital from May 2003 to December 2016. MetS was defined as the co-existence of 3 or more of 5 components (obesity, hypertension, elevated fasting glucose, decreased high-density lipoprotein-cholesterol, and hypertriglyceridemia). Logistic and Cox regression analyses were performed to evaluate the associations of MetS with pathological features and survival outcomes. Decision curve analysis and Harrell concordance index were used to determine the clinical utility of the prediction models.Of 644 patients, 157 (24.4%) had MetS. Over a median follow-up of 39 months, 269 (41.8%) experienced disease recurrence, 233 (36.2%) died, and 185 (28.7%) died of UTUC. MetS was independently associated with high-grade disease, advanced pT stage (≥pT3), and lymphovascular invasion (each P0.05). Multivariate Cox regression analysis showed that MetS was an independent factor for decreased cancer-specific survival (hazard ratio [HR]: 1.38, 95% confidence intervals [CI]: 1.01-1.89, P = 0.042) but not for recurrence-free survival (HR: 1.27, 95% CI: 0.97-1.67, P = 0.078), and overall survival (HR: 1.24, 95% CI: 0.95-1.62, P = 0.121). The estimated c-index of the multivariate models for cancer-specific survival was 0.763 compared with 0.769 when MetS added.MetS is a negative prognostic factor in UTUC. Further studies of MetS in UTUC are demanded.

117 Background: To evaluate the association between tertiary Gleason pattern (TGP) 5 and the biochemical recurrence (BCR) in patients with prostate cancer (PCa) of Gleason score (GS) 7 after radical prostatectomy(RP). Methods: This retrospective study collected 387 patients received RP and diagnosed GS 7 (3+4 or 4+3) in the West China Hospital from January 2009 to December 2017.Regardlessly the first Gleason pattern, patients were divide into 2 groups: TGP5 absence and TGP5 presence. Furthermore, we added the primary Gleason pattern to divided patients into 4 groups: GS 3+4, GS 3+4/TGP 5, Gleason 4+3, Gleason 4+3/TGP 5. Cox proportional-hazards models was used to evaluate the association between the status of TGP5 and BCR after adjusting the confounding factors with follow-up time as the underlying time scale. All the analyses were conducted with the use of statistical software packages Rnand EmpowerStats and conducted as two sides and P values less than 0.05 were considered statistical significance. Results: In the results by using Cox proportional-hazards model, regardless the primary Gleason pattern, comparing TGP5 absence (89.7%) and presence (10.3%), the risk of BCR for patients with tertiary Gleason pattern 5 presence was statistically significantly higher than absence (P = 0.02, HR = 2.24, 95%Cl: 1.12-4.49). In terms of the patients with primary Gleason pattern 4, the risk of BCR for patients with Gleason 4+3/TGP5 was statistically significantly higher than Gleason 4+3.(P = 0.02, HR = 2.56, 95%Cl: 1.16-5.67). There was a marked trend that patients with Gleason 3+4/TGP 5 has a higher risk of BCR compared with patients with Gleason 3+4, although there was no statistical difference (P = 0.58, HR = 1.82, 95%Cl: 0.22-14.96). Conclusions: The TGP5 in patients with GS 7 had strong association with the risk of BCR and it was an independent predictor for BCR. This result was more obvious in patients with GS 7 (4+3) in our study. Further researches with larger data size were needed to confirm these funding.

Objective:Endothelin has many biological activities, including regulation of the functions of the cochlear lateral wall. The present study aimed to analyse the expression of endothelin receptors in the cochlear lateral wall, and to investigate the significance of such receptors in maintaining the homeostatic environment of the cochlea.Methods:The cochleae of healthy guinea pigs were fixed, decalcified, embedded in paraffin and serially sectioned. Expression of the endothelin receptor subunits A and B in the cochlear lateral wall was examined using an immunohistochemical technique.Results:Different degrees of endothelin receptor subunit A and endothelin receptor subunit B like activity were found distributed in the cells of the cochlear lateral wall.Conclusion:These findings support the theory that endothelin, via its receptors, plays an important role in maintaining the homeostatic environment of the cochlea.