NRP1 downregulation correlates with enhanced ILC2 responses during IL-33 challenge.

Group 2 innate lymphoid cells (ILC2s) play critical roles in driving the pathogenesis of allergic airway inflammation. The mechanisms underlying the regulation of ILC2s remain to be fully understood. Here, we identified neuropilin-1 (NRP1) as a surface marker of ILC2s in response to IL-33 stimulation. NRP1 was abundantly expressed in ILC2s from lung under steady state, which was significantly reduced upon IL-33 stimulation. ILC2s with high expression of NRP1 (NRP1high) displayed lower response to IL-33, as compared with NRP1low ILC2s. Transcriptional profiling and flow cytometric analysis showed that downregulation of AKT-mTOR signalling participated in the diminished functionality of NRP1high ILC2s. These observations revealed a potential role of NRP1 in ILC2s responses under allergic inflammatory condition.

The outer membrane protein Tp92 of Treponema pallidum delays human neutrophil apoptosis via the ERK, PI3K/Akt, and NF-κB pathways.

Syphilis is a persistent sexually transmitted disease caused by infiltration of the elusive pathogen Treponema pallidum. Despite the prevalence of human polymorphonuclear neutrophils (hPMNs) within cutaneous lesions, which are characteristic of incipient syphilis, their role in T. pallidum infection remains unclear. Tp92 is the only T. pallidum helical outer membrane protein that exhibits structural features similar to those of outer membrane proteins in other gram-negative bacteria. However, the functional mechanism of this protein in immune cells remains unclear. Neutrophils are short-lived cells that undergo innate apoptosis in response to external stimuli that typically influence this process. In this study, we determined that Tp92 impedes the activation of procaspase-3 via the ERK MAPK, PI3K/Akt, and NF-κB signaling pathways, consequently suppressing caspase-3 activity within hPMNs, and thereby preventing hPMNs apoptosis. Furthermore, Tp92 could also modulate hPMNs apoptosis by enhancing the expression of the anti-apoptotic protein Mcl-1, stimulating IL-8 secretion, and preserving the mitochondrial membrane potential. These findings provide valuable insights into the molecular mechanisms underlying T. pallidum infection and suggest potential therapeutic targets for syphilis treatment.

Analysis of risk factors affecting wound healing and wound infection after meningioma resection.

To analyse the risk factors affecting wound healing and infection after spinal meningioma resection surgery. The surgical incision healing of 137 patients who underwent spinal meningioma resection at our hospital from January 2021 to January 2024 was analysed. The data collected included physical examination findings, haematological and biochemical measurements, and various scales assessed upon admission and after surgery. These data were then analysed. The surgical wound healing, infection and postoperative complications were statistically analysed. Multiple logistic regression analysis method was used to conduct risk factor analysis on corresponding indicators; the odds ratio and p value of 95% confidence interval were calculated. Factors such as age and smoking history were significantly negatively correlated with wound healing after meningioma resection (odds ratio < 1.000, p < 0.05), while preoperative albumin and platelet count were significantly positively correlated with wound healing (odds ratio > 1.000, p < 0.05). Age, WHO Meningioma Grading, preoperative albumin and preoperative platelet were significantly negatively correlated with wound infection after meningioma resection (odds ratio < 1.000, p < 0.05). The history of virus infection and history of neurological disorders were significantly positively correlated with wound infection (odds ratio > 1.000, p < 0.05). The influence of each factor is different. Age, smoking history, WHO Meningioma Grading, preoperative albumin, preoperative platelets, history of virus infection and history of neurological disorders had the greatest influence on wound healing and infection after meningioma resection.

Gut microbiota promote liver regeneration through hepatic membrane phospholipid biosynthesis.

BACKGROUND & AIMS: Hepatocyte growth and proliferation depends on membrane phospholipid biosynthesis. Short-chain fatty acids (SCFAs) generated by bacterial fermentation, delivered through the gut-liver axis, significantly contribute to lipid biosynthesis. We therefore hypothesized that dysbiotic insults like antibiotic treatment not only affect gut microbiota, but also impair hepatic lipid synthesis and liver regeneration. METHODS: Stable isotope labeling and 70% partial hepatectomy (PHx) was carried out in C57Bl/6J wild-type mice, in mice treated with broad-spectrum antibiotics, in germ-free mice and mice colonized with minimal microbiota. The microbiome was analyzed by 16S rRNA gene sequencing and microbial culture. Gut content, liver, blood and primary hepatocyte organoids were tested by mass spectrometry-based lipidomics, quantitative reverse-transcription PCR (qRT-PCR), immunoblot and immunohistochemistry for expression of proliferative and lipogenic markers. Matched biopsies from hyperplastic and hypoplastic liver tissue of patients subjected to surgical intervention to induce hyperplasia were analyzed by qRT-PCR for lipogenic enzymes. RESULTS: Three days of antibiotic treatment induced persistent dysbiosis with significantly decreased beta-diversity and richness, but a massive increase of Proteobacteria, accompanied by decreased colonic SCFAs. After PHx, antibiotic-treated mice showed delayed liver regeneration, increased mortality, impaired hepatocyte proliferation and decreased hepatic phospholipid synthesis. Expression of the lipogenic enzyme SCD1 was upregulated after PHx but delayed by antibiotic treatment. Germ-free mice essentially recapitulated the phenotype of antibiotic treatment. Phospholipid biosynthesis, hepatocyte proliferation, liver regeneration and survival were rescued in gnotobiotic mice colonized with a minimal SCFA-producing microbial community. SCFAs induced the growth of murine hepatocyte organoids and hepatic SCD1 expression in mice. Further, SCD1 was required for proliferation of human hepatoma cells and was associated with liver regeneration in human patients. CONCLUSION: Gut microbiota are pivotal for hepatic membrane phospholipid biosynthesis and liver regeneration. IMPACT AND IMPLICATIONS: Gut microbiota affect hepatic lipid metabolism through the gut-liver axis, but the underlying mechanisms are poorly understood. Perturbations of the gut microbiome, e.g. by antibiotics, impair the production of bacterial metabolites, which normally serve as building blocks for membrane lipids in liver cells. As a consequence, liver regeneration and survival after liver surgery is severely impaired. Even though this study is preclinical, its results might allow physicians in the future to improve patient outcomes after liver surgery, by modulation of gut microbiota or their metabolites.

Prognostic models for upper urinary tract urothelial carcinoma patients after radical nephroureterectomy based on a novel systemic immune-inflammation score with machine learning.

PURPOSE: This study aimed to evaluate the clinical significance of a novel systemic immune-inflammation score (SIIS) to predict oncological outcomes in upper urinary tract urothelial carcinoma(UTUC) after radical nephroureterectomy(RNU). METHOD: The clinical data of 483 patients with nonmetastatic UTUC underwent surgery in our center were analyzed. Five inflammation-related biomarkers were screened in the Lasso-Cox model and then aggregated to generate the SIIS based on the regression coefficients. Overall survival (OS) was assessed using Kaplan-Meier analyses. The Cox proportional hazards regression and random survival forest model were adopted to build the prognostic model. Then we established an effective nomogram for UTUC after RNU based on SIIS. The discrimination and calibration of the nomogram were evaluated using the concordance index (C-index), area under the time-dependent receiver operating characteristic curve (time-dependent AUC), and calibration curves. Decision curve analysis (DCA) was used to assess the net benefits of the nomogram at different threshold probabilities. RESULT: According to the median value SIIS computed by the lasso Cox model, the high-risk group had worse OS (p<0.0001) than low risk-group. Variables with a minimum depth greater than the depth threshold or negative variable importance were excluded, and the remaining six variables were included in the model. The area under the ROC curve (AUROC) of the Cox and random survival forest models were 0.801 and 0.872 for OS at five years, respectively. Multivariate Cox analysis showed that elevated SIIS was significantly associated with poorer OS (p<0.001). In terms of predicting overall survival, a nomogram that considered the SIIS and clinical prognostic factors performed better than the AJCC staging. CONCLUSION: The pretreatment levels of SIIS were an independent predictor of prognosis in upper urinary tract urothelial carcinoma after RNU. Therefore, incorporating SIIS into currently available clinical parameters helps predict the long-term survival of UTUC.

An Innovative Low-dose CT Inpainting Algorithm based on Limited-angle Imaging Inpainting Model.

BACKGROUND: With the popularity of computed tomography (CT) technique, an increasing number of patients are receiving CT scans. Simultaneously, the public's attention to CT radiation dose is also increasing. How to obtain CT images suitable for clinical diagnosis while reducing the radiation dose has become the focus of researchers. OBJECTIVE: To demonstrate that limited-angle CT imaging technique can be used to acquire lower dose CT images, we propose a generative adversarial network-based image inpainting model-Low-dose imaging and Limited-angle imaging inpainting Model (LDLAIM), this method can effectively restore low-dose CT images with limited-angle imaging, which verifies that limited-angle CT imaging technique can be used to acquire low-dose CT images. METHODS: In this work, we used three datasets, including chest and abdomen dataset, head dataset and phantom dataset. They are used to synthesize low-dose and limited-angle CT images for network training. During training stage, we divide each dataset into training set, validation set and testing set according to the ratio of 8:1:1, and use the validation set to validate after finishing an epoch training, and use the testing set to test after finishing all the training. The proposed method is based on generative adversarial networks(GANs), which consists of a generator and a discriminator. The generator consists of residual blocks and encoder-decoder, and uses skip connection. RESULTS: We use SSIM, PSNR and RMSE to evaluate the performance of the proposed method. In the chest and abdomen dataset, the mean SSIM, PSNR and RMSE of the testing set are 0.984, 35.385 and 0.017, respectively. In the head dataset, the mean SSIM, PSNR and RMSE of the testing set are 0.981, 38.664 and 0.011, respectively. In the phantom dataset, the mean SSIM, PSNR and RMSE of the testing set are 0.977, 33.468 and 0.022, respectively. By comparing the experimental results of other algorithms in these three datasets, it can be found that the proposed method is superior to other algorithms in these indicators. Meanwhile, the proposed method also achieved the highest score in the subjective quality score. CONCLUSIONS: Experimental results show that the proposed method can effectively restore CT images when both low-dose CT imaging techniques and limited-angle CT imaging techniques are used simultaneously. This work proves that the limited-angle CT imaging technique can be used to reduce the CT radiation dose, and also provides a new idea for the research of low-dose CT imaging.

Treponema pallidum Tp0751 alters the expression of tight junction proteins by promoting bEnd3 cell apoptosis and IL-6 secretion.

BACKGROUND: Neurosyphilis is a serious complication caused by the invasion of the central nervous system by Treponema pallidum subsp. pallidum (T. pallidum). However, the molecular mechanism by which T. pallidum crosses the blood-brain barrier has not been fully elucidated. OBJECTIVES: The primary purpose of this experimental design was to explore the effect of the T. pallidum adhesion protein Tp0751 on the blood-brain barrier and cerebrovascular endothelial cells. METHODS: BEnd3 cells were used to construct a monolayer blood-brain barrier model in vitro. The integrity of blood-brain barrier model was evaluated by a transendothelial cell resistance meter and transmission electron microscope after the stimulation of recombinant protein TP0751. Hoechst 33258 staining and flow cytometry were used to detect the apoptosis rate. Western blotting assay was used to measure the expression of tight junction proteins and apoptosis-related proteins. The enzyme activity detection kit was responsible for detecting the enzyme activities of Caspase 3, Caspase 8 and Caspase 9. The expression of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 at the transcription and translation levels were detected by qRT-PCR and ELISA, respectively. RESULTS: The results showed that, the tight junction structures between cells showed no obvious fragmentation, but the levels of the tight junction proteins zonula occludens-1 and occludin were reduced by the effects of Tp0751 on bEnd3 cells. In addition, further research demonstrated that after incubation with bEnd3 cells, Tp0751 induced cell apoptosis in a concentration- and time-dependent manner via the caspase 8/caspase 3 pathway. These apoptotic processes may have contributed to the changes in tight junction proteins expression. Furthermore, the Tp0751 protein may be involved in the pathogenic process by which T. pallidum crosses the blood-brain barrier by promoting secretion of the proinflammatory factor interleukin-6. CONCLUSIONS: On the whole, this study is the first to reveal and highlight that Tp0751 may affect the expression of tight junction proteins by inducing apoptosis and promoting the secretion of the inflammatory cytokine IL-6, thus playing a role in the progression of neurosyphilis caused by T. pallidum.

Chlamydia psittaci inhibits apoptosis of human neutrophils by activating P2X7 receptor expression.

This study tested the hypothesis that Chlamydia psittaci (C. psittaci) survives and multiplies in human neutrophils by activating P2X7, a nonselective cationic channel receptor expressed constitutively on the surface of these cells. Findings illustrated that P2X7 receptor expression was enhanced in C. psittaci-infected neutrophils. C. psittaci was able to inhibite spontaneous apoptosis of neutrophils through mitochondrial-induced ATP release and IL-8 production. Importantly, inhibiting ATP activation of the P2X7 receptor with AZ10606120 promotes apoptosis, while stimulating P2X7 receptor expression with BzATP delayed spontaneous apoptosis of human neutrophils, suggesting that C. psittaci inhibits apoptosis of human neutrophils by activating P2X7 receptor. This study reveals new insights into the survival advantages of the latent persistent state of C. psittaci and the mechanism by which it evades the innate immune response.

Clinicopathological and Prognostic Significance of Preoperative Prognostic Nutritional Index in Patients with Upper Urinary Tract Urothelial Carcinoma.

To investigate the prognostic value of preoperative prognostic nutritional index (PNI) to predict oncological outcome and intravesical recurrence (IVR) in upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU).This study involved the clinical data of 255 patients with UTUC who had undergone RNU from 2004 to 2019 at our institution. Patients were grouped according to an optimal value of preoperative PNI. Kaplan-Meier analyses and Cox proportional hazards models were used to analyze the associations of preoperative PNI with progression-free survival (PFS), cancer-specific survival (CSS), overall survival (OS), and IVR.Patients with low PNI were more likely to be older, have higher tumor stage, higher eGFR, and multifocal lesions. No significant association was found between PNI and CSS, IVR. In subgroup analysis according to the risk stratification, low PNI was associated with worse PFS, CSS, and OS for patients with higher risk. Multivariate analyses showed that elevated PNI was an independent prognostic indicator for PFS (P = 0.014) and OS (P = 0.048).A low PNI is an independent predictor of PFS and OS in patients with UTUC after RNU. By subgroup analysis, the prognostic value of PNI was limited to patients with higher risk. PNI may become a useful biomarker to predict oncological outcomes in patients with UTUC after RNU.

Presence of secondary bladder cancer following radical nephroureterectomy for upper tract urothelial carcinoma: characteristics, risk factors, and predictive value.

BACKGROUND: To assess the characteristics, predictive risk factors, and prognostic effect of secondary bladder cancer (SBCa) following radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC). METHODS: Using the Surveillance, Epidemiology, and End Results database, the authors analyzed clinicopathologic characteristics and survival data from 472 UTUC patients with SBCa after RNU, between 2004 and 2017. Cox's proportional hazard regression model was implemented to identify independent predictors associated with post-recurrence outcomes. The threshold for statistical significance was p < 0.05. RESULTS: In total, 200 Ta-3N0M0 localized UTUC patients with complete data were finally included. With a median follow-up of 71.0 months (interquartile ranges [IQR] 36.0 -103.8 months), 52.5% (n = 105) had died, with 30.5% (n = 61) dying of UTUC. The median time interval from UTUC to SBCa was 13.5 months (IQR 6.0-40.8 months). According to multivariable Cox regression analysis, patients with SBCa located at multiple sites, advanced SBCa stage, higher SBCa grade, elderly age and a shorter recurrence time, encountered worse cancer-specific survival (CSS), all p < 0.05. CONCLUSION: For primary UTUC patients with SBCa after radical surgery, advanced age, multiple SBCa sites, shorter recurrence time, higher SBCa stage, and grade proved to be significant independent prognostic factors of CSS. We ought to pay more attention to SBCa prevention as well as to earlier signs which may increase the likelihood of early detection. Having the ability to manage what may be seen as the superficial SBCa signs may enable us to improve survival but further research is required.

The high pH value of alkaline salt destroys the root membrane permeability of Reaumuria trigyna and leads to its serious physiological decline.

Variable climatic conditions frequently have harmful effects on plants. Reaumuria trigyna, a salt-secreting xerophytic shrub, occurs in Inner Mongolia, which has a poor environment for plant growth. To explore the physiological and molecular mechanisms of R. trigyna in response to environmental stress, this study investigated the abiotic resistance of R. trigyna in terms of growth regulation, antioxidant defense, osmotic regulation, ion transport, and ion homeostasis-related genes. R. trigyna seedlings were treated with 400 mM NaCl, 400 mM neutral salts (NaCl:Na2SO4 = 9:1), 50 mM alkaline salts (NaHCO3:Na2CO3 = 9:1), 10% polyethylene glycol (PEG), and UV-B. Seedlings under 400 mM NaCl and 400 mM neutral salt stress showed less damage. While alkaline salt, PEG, and UV stress caused more damage, specifically in oxidative damage, proline levels, electrolyte leakage, and activation of antioxidant defenses. Furthermore, under the abiotic stress treatments, the accumulation of Na+ increased while the accumulation of K+ decreased. Further analysis showed that the flow rate of Na+ and K+ under alkaline salt stress was higher than under neutral salt stress. Neutral salt induced high expression of RtNHX1 and RtSOS1, while alkaline salt induced high expression of RtHKT1, and alkaline salt stress significantly reduced the activity of root cells. These results indicated that R. trigyna seedlings were more tolerant to neutral than alkaline salts; this might be because root activity decreased at high pH levels, which impaired membrane permeability and the ion transfer system, leading to an imbalance between Na+ and K+, and in turn to excessive accumulation of reactive oxygen species (ROS) and decreased plant stress resistance.

Predictive role of ferroptosis-related long non-coding RNAs in bladder cancer and their association with immune microenvironment and immunotherapy response.

BACKGROUND: We have previously reported that ferroptosis has an important role in bladder cancer development. In this study, we aimed to further explore the possible predictive ability of ferroptosis-related long non-coding RNAs (lncRNAs) in bladder cancer and their relation with immune microenvironment and immunotherapy response. MATERIALS AND METHODS: The ferroptosis-related lncRNAs were identified by Pearson's correlation analysis. The predictive lncRNA signature was developed by univariate and multivariate regression analyses. Only the main effects of independent variables in multivariate analysis were included in this signature. The TCGA dataset was defined as the training cohort and GEO was the validation cohort in this study. All samples were grouped into a high- or low-risk group depending on risk signature. The prognostic role of lncRNA signature was explored through survival analysis and receiver operating characteristic curve (ROC) analysis in both TCGA and GEO cohorts. Additionally, the independent prognostic ability of the lncRNA signature was confirmed by multivariate independent analysis. Furthermore, the relationship between lncRNAs and immune microenvironment as well as immunotherapy response in bladder cancers was studied. RESULTS: The Kaplan-Meier curves identified significantly poorer overall survival outcomes for high-risk groups in both TCGA (p < 0.001) and GEO (p < 0.001) cohorts. The area under the curve (AUC) during ROC analysis of 1, 3, and 5 years was 0.781 ± 0.046, 0.784 ± 0.027, and 0.817 ± 0.025, respectively, in the TCGA cohort and 0.665 ± 0.177, 0.719 ± 0.068, and 0.791 ± 0.055, respectively, in the GEO cohort. The multivariate independent analysis in TCGA cohort identified age (p = 0.003), stage (p < 0.001), and signature risk score (p < 0.001) as independent risk factors for overall survival. Furthermore, this study demonstrated a significant difference in infiltration levels of various immune cells between high- and low-risk groups. The high risk group tended to have a lower expression of proteins including PD1 (p < 0.01), PD-L1 (p < 0.01), CTLA-4 (p < 0.05), etc. corresponding to various immune checkpoints. Additionally, the immunotherapy trial confirmed that the high-risk group tended to have a poorer treatment response than the low-risk group (p < 0.001). CONCLUSIONS: The ferroptosis-related lncRNAs exhibited a good predictive capacity for overall survival in bladder cancer. Additionally, they could be utilized to reveal tumour-immune microenvironment and immunotherapy responses.

Identification of a prognostic signature based on immune-related genes in bladder cancer.

Bladder cancer (BLCA) has a high incidence and recurrence rate, and the effect of immunotherapy varies from person to person. Immune-related genes (IRGs) have been shown to be associated with immunotherapy and prognosis in many other cancers, but their role in immunogenic BLCA is less well defined. In this study, we constructed an eight-IRG risk model, which demonstrated strong prognostic and immunotherapeutic predictive power. The signature was significantly related to tumor clinicopathological characteristics, tumor class, immune cell infiltration and mutation status. Additionally, a nomogram containing the risk score and other potential risk factors could effectively predict the long-term overall survival probability of BLCA patients. The enriched mechanisms identified by gene set enrichment analysis suggested that the reason why this signature can accurately distinguish high- and low-risk populations may be closely related to the different degrees of innate immune response and T cell activation in different patients.

The impact of atrial fibrillation on outcomes in patients undergoing radical prostatectomy.

PURPOSE: To assess the role of atrial fibrillation (AF) on complicating inpatient outcomes of radical prostatectomy (RP). MATERIALS AND METHODS: We identified patients treated with RP during 2012-2014 within National Inpatient Sample (NIS) database. Length of stay, cost of hospitalization, and in-hospital complications were compared between patients with or without diagnosis of AF. Propensity score matching methods and multivariable regression analysis were used to adjust for potential confounders and a trend analysis was conducted. RESULTS: Patients with AF had a significantly longer hospital stay (coefficient 0.19, 95% CI 0.09-0.29, P < 0.001) and higher cost (coefficient 0.10, 95% CI 0.06-0.15, P < 0.001). Post-operative cardiac complications were significantly higher for patients with AF (OR 16.38, 95% CI 7.72-34.74, P < 0.001), while no differences were found in other complications between the two groups. Similar results were shown in propensity score matching methods. The cardiac complications after laparoscopic RP (OR: 37.71, 95% CI 1.85-768.73, P = 0.018) and open RP (OR: 16.78, 95% CI 1.41-199.51, P = 0.026) were significantly higher than robot-assisted RP (RARP) in patients with AF. The results of trend study indicated that postoperative cardiac complication rates showed a trend of decreasing year by year while the prevalence of AF was rising. CONCLUSIONS: Perioperative AF is associated with increased cardiac complications, longer hospital stay and higher cost in PCa patients undergoing RP. RARP may be a preferred choice for patients with AF. Attention should be paid to this special patient population. Reasonable pre-operative risk stratification and standardized management should be done to decrease perioperative complications.

Molecular characteristics and phylogenetic analysis of novel goose parvovirus strains associated with short beak and dwarfism syndrome.

Short beak and dwarfism syndrome (SBDS) emerged in Cherry Valley duck flocks in China in 2015, and novel goose parvovirus (NGPV) was shown to be the etiological agent of SBDS. To date, it is not known whether SBDS-related NGPV isolates possess common molecular characteristics. In this study, three new NGPV strains (namely, SDHT16, SDJN19, and SDLC19) were isolated from diseased ducks showing typical signs of SBDS and successfully passaged in embryonated goose or Cherry Valley duck eggs. The complete genome sequences of these NGPV strains were 98.9%-99.7% identical to each other but showed slightly less similarity (95.2%-96.1% identity) to classical GPV strains. A total of 16 common amino acid substitutions were present in the VP1 proteins of six NGPV strains (SDHT16, SDJN19, SDLC19, QH, JS1, and SDLC01) compared with the classical Chinese GPV strains, nine of which were identical to those found in European GPV strain B. The non-structural protein Rep1 of the six NGPV strains had 12 common amino acid substitutions compared with the classical GPV strains. Phylogenetic analysis indicated that the Chinese NGPV strains clustered with the European SBDS-related NGPV strains, forming a separate branch that was distinct from the group formed by the classical GPV strains. The present study shows the common molecular characteristics of NGPV isolates and suggests that the Chinese NGPV isolates probably share a common ancestor with European SBDS-related NGPV strains.

The characteristics and risk factors of healthcare-seeking men with lower urinary tract symptoms in China: Initial report from the POInT group.

AIMS: To investigate the clinical characteristics of health care-seeking men presenting with lower urinary tract symptoms (LUTS) in China and to reveal risk factors for symptom severity. METHODS: This multicenter, hospital-based, cross-sectional study recruited 1477 eligible male subjects, who were at least 45 years, seeking health care at 9 participating hospitals across the mainland China. The general medical information and subjective symptoms were recorded, followed by the measurement of prostate volume, urodynamic indices, and laboratory tests for kidney function, plus glucose/lipid metabolism. Univariate and multivariate linear regression were employed for the detection of risk factors for symptom severity. RESULTS: The proportion of mild, moderate, and severe LUTS was 14.6%, 32.6%, and 52.8%, respectively, with 62.2% reporting the triple combination of storage, voiding, and postmicturition symptoms. Median prostate volume was 44.6 ml, and 71.1% were experiencing comorbidities. Thirteen independent risk factors for LUTS severity were identified, namely, nocturnal voiding episodes and the presence of straining and weak steam; the triple combination of symptom subtypes; general and nocturia quality of life; Qmax and bladder outlet obstruction index; and numbers of comorbidities, hypertension, estimated glomerular filtration rate, and cholesterol and glycosylated hemoglobin. CONCLUSIONS: The majority of health care-seeking LUTS men present with moderate-to-severe and overlapping symptoms, with a high prevalence of both lower urinary tract dysfunction and systemic comorbidities. The evidence from both urological and nonurological independent risk factors demonstrate the multifactorial nature of LUTS, for which a multidisciplinary management is essential.

Does Xylinas' nomogram accurately predict intravesical recurrence risk after radical nephroureterectomy for primary upper urinary tract urothelial carcinoma when applied to Asian populations?

OBJECTIVE: To validate a prognostic nomogram (Xylinas' nomogram) for intravesical recurrence after radical nephroureterectomy for primary upper urinary tract urothelial carcinoma patients of Asian descent. METHODS: Clinicopathological and survival data from 243 primary urinary tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision between January 2004 and May 2017 were collated. Univariate and multivariable Cox regression analyses were performed to identify independent risk factors associated with intravesical recurrence-free survival. External validation was determined using regression coefficients abstracted from previously published data. Performance was then quantified through calibration and discrimination, according to concordance indexes (c-index) in receiver operating characteristic curves. RESULTS: 163 patients met our eligibility criteria and were finally included in this study. At a median follow-up of 60 months, intravesical recurrence occurred in 29.4% (n = 48). Multivariable analysis revealed that being male, ureteral tumor location, tumor multifocality and previous bladder cancer were independent prognostic factors of intravesical recurrence-free survival. When Xylinas' nomogram was applied to our cohort, the discriminatory power was found to be roughly equivalent with a c-index of 68.3% for the reduced model and 68.4% for the full model. Calibration plots also revealed intravesical recurrence predictions at 3, 6, 12, 18, 24 and 36 months had relative concordance. Contrasting the respective performances of the reduced and full model suggests there is no significant difference between the two (all P > 0.05). CONCLUSIONS: This nomogram appears accurate at predicting intravesical recurrence after radical nephroureterectomy for primary urinary tract urothelial carcinoma in Asian populations. However, it remains necessary to data mine for unknown prognostic factors for optimization. Further external validation is required across larger, ethically diverse populations before applying this nomogram in clinical practice.

Developing a nomogram for predicting intravesical recurrence after radical nephroureterectomy: a retrospective cohort study of mainland Chinese patients.

OBJECTIVE: To evaluate the role of Ki-67 in predicting subsequent intravesical recurrence following radical nephroureterectomy and to develop a predictive nomogram for upper tract urothelial carcinoma patients. METHODS: This retrospective analysis involved 489 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision. The data set was randomly split into a training cohort of 293 patients and a validation cohort of 196 patients. Immunohistochemical analysis was used to assess the immunoreactivity of the biomarker Ki-67 in the tumor tissues. A multivariable Cox regression model was utilized to identify independent intravesical recurrence predictors after radical nephroureterectomy before constructing a nomographic model. Predictive accuracy was quantified using time-dependent receiver operating characteristic curve. Decision curve analysis was performed to evaluate the clinical benefit of models. RESULTS: With a median follow-up of 54 months, intravesical recurrence developed in 28.2% of this sample (n = 137). Tumor location, multifocality, pathological T stage, surgical approach, bladder cancer history and Ki-67 expression levels were independently associated with intravesical recurrence (all P < 0.05). The full model, which intercalated Ki-67 with traditional clinicopathological parameters, outperformed both the basic model and Xylinas' model in terms of discriminative capacity (all P < 0.05). Decision-making analysis suggests that the more comprehensive model can also improve patients' net benefit. CONCLUSIONS: This new model, which intercalates the Ki-67 biomarker with traditional clinicopathological factors, appears to be more sensitive than nomograms previously tested across mainland Chinese populations. The findings suggest that Ki-67 could be useful for determining risk-stratified surveillance protocols following radical nephroureterectomy and in generating an individualized strategy based around intravesical recurrence predictions.

Transcriptional mutagenesis mediated by 8-oxoG induces translational errors in mammalian cells.

Reactive oxygen species formed within the mammalian cell can produce 8-oxo-7,8-dihydroguanine (8-oxoG) in mRNA, which can cause base mispairing during gene expression. Here we found that administration of 8-oxoGTP in MTH1-knockdown cells results in increased 8-oxoG content in mRNA. Under this condition, an amber mutation of the reporter luciferase is suppressed. Using second-generation sequencing techniques, we found that U-to-G changes at preassigned sites of the luciferase transcript increased when 8-oxoGTP was supplied. In addition, an increased level of 8-oxoG content in RNA induced the accumulation of aggregable amyloid ß peptides in cells expressing amyloid precursor protein. Our findings indicate that 8-oxoG accumulation in mRNA can alter protein synthesis in mammalian cells. Further work is required to assess the significance of these findings under normal physiological conditions.

Enhanced store-operated calcium entry (SOCE) exacerbates motor neurons apoptosis following spinal cord injury.

Spinal cord injury is pathologically characterized by the loss of motor function caused by neurons apoptosis. Store-operated calcium entry (SOCE) is widely known to dictate the apoptosis of various cell types. To examine SOCE in spinal cord injury and explore the role of SOCE in apoptosis, patients with spinal cord injury (SCI) and SCI mouse models were included. Expression of SOCE components and apoptosis-related proteins were examined by Western blotting. Calcium imaging was used to assess SOCE activity. As a result, we confirmed the enhanced levels of ORAI1 and STIM1 in SCI patients and SCI mouse models. In vitro study, tunicamycin impaired the viability of VSC4.1 cells (motoneuron-neuroblastoma hybrid cell line) and increased SOCE activity, the effects of which could be abolished by 2-APB. Furthermore, tunicamycinreduced BCL-2/BAX ratio was also reversed by 2-APB. Additionally, EdU assay and DCFH-DA staining confirmed the regulatory role of 2-APB in proliferation and ROS production. Of note is the improved hindlimb motor function and alleviated depression by 2-APB administration. Therefore, we conclude that SOCE may contribute to the pathogenesis of SCI by exacerbating the apoptosis of motoneurons.