UPK3A+ umbrella cell damage mediated by TLR3-NR2F6 triggers programmed destruction of urothelium in Hunner-type interstitial cystitis/painful bladder syndrome.

Urothelial damage and barrier dysfunction emerge as the foremost mechanisms in Hunner-type interstitial cystitis/bladder pain syndrome (HIC). Although treatments aimed at urothelial regeneration and repair have been employed, their therapeutic effectiveness remains limited due to the inadequate understanding of specific cell types involved in damage and the lack of specific molecular targets within these mechanisms. Therefore, we harnessed single-cell RNA sequencing to elucidate the heterogeneity and developmental trajectory of urothelial cells within HIC bladders. Through reclustering, we identified eight distinct clusters of urothelial cells. There was a significant reduction in UPK3A+ umbrella cells and a simultaneous increase in progenitor-like pluripotent cells (PPCs) within the HIC bladder. Pseudotime analysis of the urothelial cells in the HIC bladder revealed that cells faced challenges in differentiating into UPK3A+ umbrella cells, while PPCs exhibited substantial proliferation to compensate for the loss of UPK3A+ umbrella cells. The urothelium in HIC remains unrepaired, despite the substantial proliferation of PPCs. Thus, we propose that inhibiting the pivotal signaling pathways responsible for the injury to UPK3A+ umbrella cells is paramount for restoring the urothelial barrier and alleviating lower urinary tract symptoms in HIC patients. Subsequently, we identified key molecular pathways (TLR3 and NR2F6) associated with the injury of UPK3A+ umbrella cells in HIC urothelium. Finally, we conducted in vitro and in vivo experiments to confirm the potential of the TLR3-NR2F6 axis as a promising therapeutic target for HIC. These findings hold the potential to inhibit urothelial injury, providing promising clues for early diagnosis and functional bladder self-repair strategies for HIC patients. © 2024 The Pathological Society of Great Britain and Ireland.

Potential regulatory effects of stem cell exosomes on inflammatory response in ischemic stroke treatment.

The high incidence and disability rates of stroke pose a heavy burden on society. Inflammation is a significant pathological reaction that occurs after an ischemic stroke. Currently, therapeutic methods, except for intravenous thrombolysis and vascular thrombectomy, have limited time windows. Mesenchymal stem cells (MSCs) can migrate, differentiate, and inhibit inflammatory immune responses. Exosomes (Exos), which are secretory vesicles, have the characteristics of the cells from which they are derived, making them attractive targets for research in recent years. MSC-derived exosomes can attenuate the inflammatory response caused by cerebral stroke by modulating damage-associated molecular patterns. In this review, research on the inflammatory response mechanisms associated with Exos therapy after an ischemic injury is discussed to provide a new approach to clinical treatment.

Smoking is an independent risk factor for stricture recurrence after the urethroplasty: a systematic review and meta-analysis

ABSTRACT Objective: To clarify the association between smoking and stricture recurrence after urethroplasty. Materials and Methods: Pubmed, Web of Science, Embase, and Cochrane databases were searched with keywords: "urethroplasty," "buccal mucosa graft urethroplasty," "oral mucosa graft urethroplasty," "excision and primary anastomosis urethroplasty," "urethral stricture recurrence" until July 1, 2022. Inclusion and exclusion criteria were based on PICOS principles. The quality of included studies was assessed by Newcastle-Ottawa Scale (N.O.S.) system. Hazard ratio (H.R.), odds ratio (OR), and relative risk (RR) with 95% confidence interval (CI) were extracted or re-calculated from included studies. Meta-analysis was performed with Stata 15.0 based on univariate and multivariate data separately. Sensitivity analysis was performed to test the stability of the meta-analysis. I2 was calculated to evaluate heterogeneity. Publication biases were assessed by Egger's and Begg's tests. Funnel plots of univariate analysis and multivariate analysis were also offered. Results: Twenty one studies with 6791 patients were involved in this meta-analysis. The analysis results of the two stages were consistent. In the univariate meta-analysis stage, 18 studies with 5811 patients were pooled, and the result indicated that smoking might promote stricture recurrence (RR=1.32, P=0.001). Based on the adjusted estimate, 11 studies with 3176 patients were pooled in the multivariate meta-analysis stage, and the result indicated that smoking might promote stricture recurrence (RR=1.35, P=0.049). There was no significant heterogeneity in both the univariate and multivariate stages. Conclusion: Our study demonstrates that smoking may prompt stricture recurrence after the urethroplasty. Quitting smoking may be a good option for patients undergoing urethroplasty surgery.

The association between heavy metal exposure and erectile dysfunction in the United States.

Literature regarding the impacts of heavy metal exposure on erectile dysfunction (ED) is scarce. We aimed to evaluate the correlation between 10 urinary metals and ED in a large, nationally representative adult male sample. The dataset was extracted from the National Health and Nutrition Examination Survey (NHANES) during the period of 2001-2002 and 2003-2004. Weighted proportions and multivariable logistic regression analysis adjusted for confounding variables were utilized to determine the relationship between metal exposure and ED. Weighted quantile sum (WQS) regression was utilized to evaluate the impact of a mixture of urinary metals on ED. A total of 1328 participants were included in our study. In multivariable logistic regression analysis, cobalt (Co) and antimony (Sb) were positively associated with ED (odds ratio [OR]: 1.36, 95% confidence interval [CI]: 1.10-1.73, P = 0.020; and OR: 1.41, 95% CI: 1.12-1.77, P = 0.018, respectively) after full adjustment. Men in tertile 4 for Co (OR: 1.49, 95% CI: 1.02-2.41, P for trend = 0.012) and Sb (OR: 1.53, 95% CI: 1.08-2.40, P for trend = 0.041) had significantly higher odds of ED than those in tertile 1. Furthermore, the WQS index was significantly linked with increased odds of ED after full adjustment (OR: 1.31, 95% CI: 1.04-1.72, P < 0.05). Our study expanded on previous literature indicating the possible role of heavy metal exposure in the etiology of ED. The evaluation of heavy metal exposure should be included in the risk assessment of ED.

The effect of COVID-19 vaccines on sperm parameters: a systematic review and meta-analysis.

Published data were gathered for a meta-analysis to determine the difference in sperm parameters before and after administration of different types of coronavirus disease 2019 (COVID-19) vaccines, because the reproductive toxicity of COVID-19 vaccines has not yet been evaluated in clinical trials and COVID-19 has been associated with decreases in sperm quality. The preferred procedures for systematic reviews and meta-analyses were followed in the conduct and reporting of this study. The average sperm parameters of all sperm donors' multiple sperm donations were compared before and after receiving various COVID-19 vaccinations. Semen volume, total sperm motility, total sperm count, morphological change, and sperm concentration were the primary outcome measures. We compiled and analyzed the results of six studies on total sperm motility, six studies on semen volume, six studies on sperm concentration, two studies on morphological change, and two studies on total sperm count. Parameter comparisons with patients who had and had not been vaccinated were only reported in one of the included studies. When different types of COVID-19 vaccine injections were compared, no discernible differences in parameters were observed. According to the available data, the parameters of semen are unaffected by inactivated or messenger RNA (mRNA) COVID-19 vaccinations. To support these findings, additional prospectively designed research is required.

Smoking is an independent risk factor for stricture recurrence after the urethroplasty: a systematic review and meta-analysis.

OBJECTIVE: To clarify the association between smoking and stricture recurrence after urethroplasty. MATERIALS AND METHODS: Pubmed, Web of Science, Embase, and Cochrane databases were searched with keywords: "urethroplasty," "buccal mucosa graft urethroplasty," "oral mucosa graft urethroplasty," "excision and primary anastomosis urethroplasty," "urethral stricture recurrence" until July 1, 2022. Inclusion and exclusion criteria were based on PICOS principles. The quality of included studies was assessed by Newcastle-Ottawa Scale (N.O.S.) system. Hazard ratio (H.R.), odds ratio (OR), and relative risk (RR) with 95% confidence interval (CI) were extracted or re-calculated from included studies. Meta-analysis was performed with Stata 15.0 based on univariate and multivariate data separately. Sensitivity analysis was performed to test the stability of the meta-analysis. I2 was calculated to evaluate heterogeneity. Publication biases were assessed by Egger's and Begg's tests. Funnel plots of univariate analysis and multivariate analysis were also offered. RESULTS: Twenty one studies with 6791 patients were involved in this meta-analysis. The analysis results of the two stages were consistent. In the univariate meta-analysis stage, 18 studies with 5811 patients were pooled, and the result indicated that smoking might promote stricture recurrence (RR=1.32, P=0.001). Based on the adjusted estimate, 11 studies with 3176 patients were pooled in the multivariate meta-analysis stage, and the result indicated that smoking might promote stricture recurrence (RR=1.35, P=0.049). There was no significant heterogeneity in both the univariate and multivariate stages. CONCLUSION: Our study demonstrates that smoking may prompt stricture recurrence after the urethroplasty. Quitting smoking may be a good option for patients undergoing urethroplasty surgery.

Stone removing efficiency and safety comparison between single use ureteroscope and reusable ureteroscope: a systematic review and meta-analysis.

BACKGROUND: Urologists are gradually beginning to use single-use ureteroscopes (sufURSs), despite a lack of high-level evidence as to their efficacy and safety. This systematic review was registered on PROSPERO (no. CRD42020181808). METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were searched for studies published before October 1, 2020. Jadad score tools were used to evaluate the quality of the included randomized controlled trials (RCTs) and the Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included nonrandomized studies. Two researchers independently extracted data according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) principles. A data synthesis was performed using Stata 15.0. Heterogeneity was mainly evaluated with I2 tests. In addition to funnel plots, Egger's and Begg's tests were used to detect publication bias. A sensitivity analysis was also performed. Stone-free rates and postoperative complications were the 2 primary outcomes; operation-time data were also extracted. RESULTS: Six studies (comprising 887 patients) containing the efficacy data and 5 studies (comprising 952 patients) containing the safety data that were finally included in the quantitative analysis. In relation to stone removal, no significant difference was found in terms of efficacy [Mantel-Haenszel statistic (M-H), relative risk (RR): 1.01, 95% confidence interval (CI): 0.96-1.07, P=0.658) or safety (M-H, RR: 1.30, 95% CI: 0.96-1.75, P=0.093) between the sufURS and the reusable flexible ureteroscope (rfURS), and no significant heterogeneity was found. A publication bias was detected in the efficacy comparison; however, the trim-and-fill analysis indicated that the original synthesis results remained stable. CONCLUSIONS: In relation to stone removal, sufURSs were found to be comparable to rfURS, and no compromising complications were found. However, the results should be treated with caution due to limitations related to the small number of studies included in the analysis.

Preoperative urine nitrite versus urine culture for predicting postoperative fever following flexible ureteroscopic lithotripsy: a propensity score matching analysis.

PURPOSE: Multiple studies have reported that preoperative positive urine culture is an independent risk factor for postoperative fever (POF) after ureteroscopy (URS). Urine nitrite is associated urinary tract infections (UTIs). However, none of studies has explored the role of urine nitrite in the prediction of POF after flexible URS (fURS). METHODS: Patients who underwent fURS by the same surgeon between 2009 and 2019 were screened. Sensitivity and specificity of urine culture and urine nitrite were calculated. Propensity score (PS) matching was performed to get a baseline-balanced retrospective cohort to avoid potential bias. Receiver operating characteristic-area under the curve (ROC-AUC) calculated was used to determine the predictive power of models. Decision curve analysis (DCA) was plotted to obtain the clinical benefit of the models. RESULTS: Poseoperative fever (POF) is defined as the temperature of the patient higher than 38 ℃ within 72 h after operation, with no sign of infection in other systems. 31(2.8%) of 1095 cases had POF after fURL. Urine nitrite had a better specificity than urine culture for POF diagnosis (P < 0.001). After the PS matching, a well-balanced cohort of 24 POF group and 96 no-POF group was produced. The mean AUC from the bootstrap resampling method for urine nitrite model (AUC: 0.8736; 95% CI: 0.8731-0.8743) was significantly increased than that of the urine culture model (AUC: 0.8385; 95% CI: 0.8378-0.8392). The application of two kinds of POF predicting models could bring clinical net benefit when the probability is < 35%. However, urine nitrite model showed a better clinical net benefit acquirement compared to the urine culture model. CONCLUSION: Preoperative positive urine nitrite may play a pivotal role in the prediction of POF after fURS and needs to be validated by future evidence.

Preoperative positive urine nitrite and albumin-globulin ratio are independent risk factors for predicting postoperative fever after retrograde Intrarenal surgery based on a retrospective cohort.

BACKGROUND: To determine risk factors for postoperative fever (POF) after retrograding intrarenal surgery (RIRS) and a nomogram for prediction of POF in patients undertaking RIRS has been developed based on the risk factors found. METHODS: This is a retrospective designed-study. A continuous cohort from a single-center database that consisted of 1095 cases undertaking RIRS with complete preoperative medical records from January 2009 to December 2018 was obtained. Independent risk factors were identified according to the multi-variate logistics regression and a further nomogram was developed. The performance of the nomogram was evaluated through three aspects including net clinical benefit, calibration, and discrimination. RESULTS: A total of 31(2.8%) cases had POF after the RIRS. Risk factors included time in RIRS ≥30mins (only the flexible scope use period) (OR: 2.16, 95%CI; 1.01-4.62, P = 0.047), preoperative positive urine culture (OR: 2.55, 95%CI; 1.01-6.42, P = 0.047), preoperative positive urine nitrite (OR: 9.09, 95%CI; 2.99-27.64, P < 0.001), Albumin/globulin ratio (AGR) (OR: 0.14, 95%CI; 0.03-0.74, P = 0.020) were further included in the nomogram to predict the POF probability for individuals. The Hosmer-Lemeshow test showed a goodness-of-fit. The calibration curve demonstrated good agreement between observation and prediction. Decision curve analysis (DCA) demonstrated it was clinical use in RIRS. CONCLUSIONS: The preoperative urine nitrite, AGR, RIRS time, and preoperative urine culture are found to be independent risk factors associated with POF after RIRS. Then we have developed a nomogram taking these factors into account that accurately predicted POF after RIRS.

Risk Factors of Infectious Complications after Ureteroscopy: A Systematic Review and Meta-Analysis Based on Adjusted Effect Estimate.

Background: Multiple studies have reported that gender, pre-operative stent insertion, positive pre-operative urine culture results, and diabetes mellitus are associated with infectious complication after ureteroscopy. A previous meta-analysis focused on this topic is based, however, on crude estimate. Further analysis based on adjusted estimates is needed. Methods: PubMed, Web of Science, Embase, and the Cochrane Library database were searched with ureteroscopy, ureteroscopies, ureteroscopic surgical procedures, ureteroscopic surgery, ureteroscopic lithotripsy, flexible ureteroscopic lithotripsy, ureteroscopy (URS), flexible ureterorenoscopy, risk factor, predictor, predicting model, and nomogram until December 15, 2019. The quality of research was evaluated by Newcastle-Ottawa Scale system. Odds ratio (OR) and 95% confidence intervals (CI) of each risk factor were extracted. Meta-analysis was performed with Stata 15.0 software. Heterogeneity was assessed by I2. Publication bias was tested by the Egger test, and funnel plot. Meta-regressions and subgroup analysis were further performed. Results: There were 16 studies; 12,357 patients finally were included in this meta-analysis. The association between gender (OR = 1.82, 95% CI: 1.48-2.23, I2 = 0%, p = 0.701), pre-operative ureteric stent insertion (OR = 1.91, 95% CI: 1.26-2.91, I2 = 40.4%, p = 0.109), diabetes mellitus (OR: 1.40, 95% CI: 1.07-1.85, I2 = 34.1%, p = 0.168), positive urine culture before URS (OR: 2.18, 95% CI: 1.34-3.57, I2 = 47.2%, p = 0.092), operation duration (OR: 1.03, 95% CI: 1.01-1.04, I2 = 70.6%, p = 0.001) and infectious complications was positively significant. All four pooled results were different from results of meta-analysis based on crude estimate. Conclusion: Female gender, pre-operative ureteric stent insertion, diabetes mellitus, positive urine culture results before URS, and operation duration are risk factors for infectious complications after URS. Meta-analysis based on adjusted estimates may be more convincing.

Unveiling tropospheric ozone by the traditional atmospheric model and machine learning, and their comparison:A case study in hangzhou, China.

Tropospheric ozone in the surface air has become the primary atmospheric pollutant in Hangzhou, China, in recent years. Previous analysis is not enough to decode it for better regulation. Therefore, we use the traditional atmospheric model, Weather Research and Forecasting coupled with Community Multi-scale Air Quality (WRF-CMAQ), and machine learning models, Extreme Learning Machine (ELM), Multi-layer Perceptron (MLP), Random Forest (RF) and Recurrent Neural Network (RNN) to analyze and predict the ozone in the surface air in Hangzhou, China, using meteorology and air pollutants as input. We firstly quantitatively demonstrate that the dew-point deficit, instead of temperature and relative humidity, is the predominant meteorological factor in shaping tropospheric ozone. Urban heat island, daily direct solar radiation time, wind speed and wind direction play trivial role in impacting tropospheric ozone. NO2 is the primary influential factors both for hourly ozone and daily O3-8 h due to the titration effect. The most environmental-friendly way to mitigate the ozone pollution is to lower the volatile organic compounds (VOCs) with the highest ozone formation potentials. We deduce that the tropospheric ozone formation process tends to be not only non-linear but also non-smooth. Compared with the traditional atmospheric models, machine learning, whose characteristics are rapid convergence, short calculating time, adaptation of forecasting episodes, small program memory, higher accuracy and less cost, is able to predict tropospheric ozone more accurately.

Enucleation of the prostate for benign prostatic hyperplasia thulium laser versus holmium laser: a systematic review and meta-analysis.

To evaluate the clinical efficacy and safety of thulium laser vapoenucleation/enucleation of the prostate (ThuEP) versus holmium laser enucleation of the prostate (HoLEP) in the management of benign prostatic hyperplasia (BPH). A systematic literature search was performed using PubMed, Embase, and Web of Science to identify eligible studies published before July 2018. Meta-analysis of extracted data was performed with RevMan version 5.3. We chose the fixed- or random-effect model to fit the pooled heterogeneity. Five eligible studies including two randomized controlled trials (RCTs) and three non-RCTs involving 1010 patients were enrolled in our meta-analysis. ThuEP provided less enucleation time when compared with HoLEP (WMD = - 7.73, 95% CI - 14.39-1.07, P = 0.02). During the 1st, 6th, and 12th months of postoperative follow-ups, statistically significant differences were found in Qmax (WMD = 2.05, 95% CI 0.52~3.58) and PVR (WMD = - 6.50, 95% CI - 7.35~- 5.66, P < 0.001) in the 1st month after the operation, also in IPSS (IPSS: WMD = - 1.29, 95% CI - 2.39~- 0.19, P = 0.02) in the 12th month after the operation. As regards other perioperative, postoperative parameters, and complication rates, we found no significant difference. Both ThuEP and HoLEP provided satisfactory micturition improvement with low morbidity after the 1st and 6th months of the operation. However, ThuEP showed higher enucleation efficacy and less intraoperative blood loss and may get a better outcome as compared to the HoLEP group in the early postoperative period with regard to Qmax/PVR and IPSS after the 1st and 12th months of the operation respectively.

[Clinical Research on the Post-operative Hemodynamics Changes in Donors after Living Donor Liver Transplantation].

OBJECTIVE: To investigate the postoperative hemodynamics changes and their influence factors in the donors after right lobe living donor liver transplantation. METHODS: A total of 53 consecutive living donors from Dec 2010 to Aug 2015 who underwent donor right lobe hepatectomy were retrospectively analyzed. We measured residual liver hemodynamics with color doppler ultrasound, detected liver stiffness by transient elastography, also analyzed postoperative liver function, hemodynamics, and the long term variation tendency of hepatocirrhosis and spleen. RESULTS: One week after operation, transient liver damage was observed. Post-operative hemodynamics within the follow-up time showed:portal vein diameter was gradually increasing, the velocity decreased gradually;Hepatic vein diameter increased, and the velocity decreased gradually. There was a negative correlation between portal vein diameter and portal vein velocity (P=0.012, r=-3.11). Liver stiffness (Kpa value) decreased gradually with time, while spleen volume gradually increased. Correlation analysis showed that postoperative liver stiffness (Kpa value) was negatively related to portal vein diameter (P=0.013, r=-0.338) and positively related to hepatic venous velocity (P=0.038,r=0.246). CONCLUSIONS: The donor presented a transient liver injury after operation, but tended to be recovery after one week. Despite post-operative hemodynamic undergo a series of changes, but it does not affect the post-operative long-term donor safety.

Relevant markers of cancer stem cells indicate a poor prognosis in hepatocellular carcinoma patients: a meta-analysis.

The potential prognostic value of stem cell markers is variably reported, such as CD133 and epithelial cell adhesion molecule. However, their clinical value and significance in hepatocellular carcinoma (HCC) remain controversial. The aim of this study was to carry out a meta-analysis of literature evaluating CD133 and epithelial cell adhesion molecule expression as prognostic factors in HCC and to determine the association between cancer stem cells (CSCs) and common clinical and pathologic features of HCC. The relevant literature was identified using Science Direct, EMBASE, and PubMed. Outcome measures included disease-free survival, overall survival, and relevant pathological parameters. Meta-analyses were carried out using Review Manager, version 5.2. Twelve eligible articles involving 1344 patients were included. Meta-analyses showed that the presence of CSCs was significantly associated with a poor histological grade (OR=3.16, P=0.003) and elevated serum α-fetoprotein level (OR=2.68, P<0.00001). However, there were no significant relations between the presence of CSCs and tumor size, tumor stage, hepatitis, or cirrhosis. The presence of CSCs was significantly associated with poor survival, including overall survival (HR=1.62, P<0.00001) and disease-free survival (HR=1.85, P<0.00001). On the basis of current retrospective evidence, the presence of CSCs is associated with poor histopathologic grade and worse survival in patients with HCC and CD133 plays a significant role in predicting the clinical outcome. Further extensive experimental and clinical research should be carried out to evaluate the role of these markers in clinical practice.