Isolation of endophytes from Dioscorea nipponica Makino for stimulating diosgenin production and plant growth.

KEY MESSAGE: Both bacterial and fungal endophytes exhibited one or more plant growth-promoting (PGP) traits. Among these strains, the Paenibacillus peoriae SYbr421 strain demonstrated the greatest activity in the direct biotransformation of tuber powder from D. nipponica into diosgenin. Endophytes play crucial roles in shaping active metabolites within plants, significantly influencing both the quality and yield of host plants. Dioscorea nipponica Makino accumulates abundant steroidal saponins, which can be hydrolyzed to produce diosgenin. However, our understanding of the associated endophytes and their contributions to plant growth and diosgenin production is limited. The present study aimed to assess the PGP ability and potential of diosgenin biotransformation by endophytes isolates associated with D. nipponica for the efficient improvement of plant growth and development of a clean and effective approach for producing the valuable drug diosgenin. Eighteen bacterial endophytes were classified into six genera through sequencing and phylogenetic analysis of the 16S rDNA gene. Similarly, 12 fungal endophytes were categorized into 5 genera based on sequencing and phylogenetic analysis of the ITS rDNA gene. Pure culture experiments revealed that 30 isolated endophytic strains exhibited one or more PGP traits, such as nitrogen fixation, phosphate solubilization, siderophore synthesis, and IAA production. One strain of endophytic bacteria, P. peoriae SYbr421, effectively directly biotransformed the saponin components in D. nipponica. Moreover, a high yield of diosgenin (3.50%) was obtained at an inoculum size of 4% after 6 days of fermentation. Thus, SYbr421 could be used for a cleaner and more eco-friendly diosgenin production process. In addition, based on the assessment of growth-promoting isolates and seed germination results, the strains SYbr421, SYfr1321, and SYfl221 were selected for greenhouse experiments. The results revealed that the inoculation of these promising isolates significantly increased the plant height and fresh weight of the leaves and roots compared to the control plants. These findings underscore the importance of preparing PGP bioinoculants from selected isolates as an additional option for sustainable diosgenin production.

Polyfluoroalkyl chemicals and the risk of kidney stones in US adults: A population-based study.

The potential nephrotoxicity of polyfluoroalkyl chemicals (PFCs) have received extensive attention. However, the relationship between PFCs and the risk of kidney stones remain unclear. This study aimed to examine the level of PFCs in the US population and its relationship with the risk of kidney stones. We investigated the serum levels of six PFCs in 8453 adult participants (≥20 years) from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016, including perfluorodecanoic acid (PFDE), perfluorohexane sulfonic acid (PFHS), 2-(N-methyl-perfluorooctane sulfonamido) acetate (MPAH), perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUA), and perfluorododecanoic acid (PFDO). Logistic regression model was used to evaluate the correlation between PFCs and kidney stones. Of the 8453 participants, 787 self-reported a history of kidney stones. After adjusting for gender, age, race, education, marital status, body mass index (BMI), hypertension, diabetes and estimated glomerular filtration rate (eGFR), we found that total PFCs and PFHS were positively correlated with the risk of kidney stones. Compared with the lowest tertile, the odds ratios with 95% confidence intervals (CI) with increasing tertiles were 1.30 (95% CI,1.08-1.59, p = 0.007) and 1.25 (95 CI%,1.00-1.52, p = 0.024) for total PFCs and 1.24 (95 CI%,1.03-1.51, p = 0.032), and 1.35 (95 CI,1.10-1.68, p = 0.005) for PFHS. Our study shows that total PFCs and PFHS were associated with an increased risk of kidney stones.

Cystatin C in Evaluating Renal Function in Ureteral Calculi Hydronephrosis in Adults.

BACKGROUND: Serum cystatin C (CysC) is still becoming used as a marker of renal function but is far from being commonly used worldwide. The purpose of this study was to characterize the ureteral calculi patients with hydronephrosis-caused CysC changes in renal function. METHODS: To better reflect the changes of renal function, we constructed models of ureteral obstruction in rats to mimic the hydronephrosis caused by human ureteral calculi. Moreover, our study included 200 patients diagnosed with ureteral calculi in our hospital between June 2017 and 2018. We compared the estimated glomerular filtration rate using different equations based on CysC and/or serum creatinine (SCr). RESULTS: We found that the expression of CysC and SCr increased with the prolonged obstruction time by enzyme linked immunosorbent assay. Moreover, quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry further demonstrated that the expression of CysC increases with the degree of hydronephrosis. Among 200 patients with ureteral calculi, 40 (20.0%) had no hydronephrosis, 110 (55.0%) had mild hydronephrosis, 32 (16.0%) had moderate hydronephrosis and 18 (9.0%) had severe hydronephrosis. As the degree of hydronephrosis increased, the expression of neutrophil percentage, CysC, blood urea nitrogen, SCr and serum uric acid also increased. Multivariate analyses demonstrated that only CysC was an independent risk factor for hydronephrosis (p = 0.003). In addition, CysC and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) CysC equation showed the highest veracity in renal function estimation of patients with hydronephrosis caused by ureteral calculus. CONCLUSION: For patients with hydronephrosis caused by ureteral calculi, CysC better reflects the changes in renal function, and the CKD-EPI CysC equation has the highest accuracy.

Expression of the Thermobifida fusca xylanase Xyn11A in Pichia pastoris and its characterization.

BACKGROUND: Xylan is a major component of plant cells and the most abundant hemicellulose. Xylanases degrade xylan into monomers by randomly cleaving ß-1,4-glycosidic bonds in the xylan backbone, and have widespread potential applications in various industries. The purpose of our study was to clone and express the endoxylanase gene xynA of Thermobifida fusca YX in its native form and with a C-terminal histidine (His) tag in Pichia pastoris X-33. We analyzed and compared these two forms of the protein and examined their potential applications in various industries. RESULTS: The xynA gene from T. fusca YX was successfully cloned and expressed using P. pastoris X-33. We produced a recombinant native form of the protein (rXyn11A) and a C-terminal His-tagged form of the desired protein (rXyn11A-(His)6). The specific activities of rXyn11A and rXyn11A-(His)6 in culture supernatants approached 149.4 and 133.4 U/mg, respectively. These activities were approximately 4- and 3.5-fold higher than those for the non-recombinant wild-type Xyn11A (29.3 U/mg). Following purification, the specific activities of rXyn11A and rXyn11A-(His)6 were 557.35 and 515.84 U/mg, respectively. The specific activity of rXyn11A was 8% higher than that of rXyn11A-(His)6. Both recombinant xylanases were optimally active at 80°C and pH 8.0, and exhibited greater than 60% activity between pH 6-9 and 60-80°C. They exhibited similar pH stability, while rXyn11A exhibited better thermostability; N-glycosylation enhanced the thermostability of both recombinant xylanases. The products of beechwood xylan hydrolyzed by both xylanases included xylobiose, xylotriose, xylotetraose and xylopentaose. CONCLUSIONS: The C-terminal His tag had adverse effects when added to the Xyn11A protein. The thermostability of both recombinant xylanases was enhanced by N-glycosylation. Their stabilities at a high pH and temperature indicate their potential for application in various industries.

Statin use and risk of kidney cancer: a meta-analysis of observational studies and randomized trials.

AIM: Clinical studies have shown that statin use may modify the risk of kidney cancer. However, these studies yielded different results. To quantify the association between statin use and risk of kidney cancer, we performed a detailed meta-analysis of published studies regarding this subject. METHODS: A literature search was carried out using MEDLINE, EMBASE and the Cochrane database between January 1966 and October 2012. Prior to performing a meta-analysis, the studies were evaluated for publication bias and heterogeneity. Fixed effect and random effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity analysis were also performed. RESULTS: A total of 12 (two randomized controlled trials, five cohort, and five case-control) studies contributed to the analysis. There was heterogeneity among the studies but no evidence of publication bias. Pooled results indicated a non-significant decrease of total kidney cancer risk among all statin users (RR = 0.92, 95% CI 0.71, 1.19). Long term statin use did not significantly affect the risk of total kidney cancer (RR = 1.01, 95% CI 0.83, 1.22). In our subgroup analyses, the results were not substantially affected by study design, confounder adjustment and gender. Furthermore, sensitivity analysis confirmed the stability of the results. CONCLUSION: The findings of this meta-analysis suggested that there was no association between statin use and risk of kidney cancer. More studies, especially randomized controlled trials and high quality cohort studies with larger sample size and well controlled confounding factors, are needed to confirm this association in the future.

The functions and mechanisms of RNA modification in prostate: Current status and future perspectives.

The increasing incidence and mortality of prostate cancer worldwide significantly impact the life span of male patients, emphasizing the urgency of understanding its pathogenic mechanism and associated molecular changes that regulate tumor progression for effective prevention and treatment. RNA modification, an important post-transcriptional regulatory process, profoundly influences tumor cell growth and metabolism, shaping cell fate. Over 170 RNA modification methods are known, with prominent research focusing on N6-methyladenosine, N7-methylguanosine, N1-methyladenosine, 5-methylcytidine, pseudouridine, and N4-acetylcytidine modifications. These alterations intricately regulate coding and non-coding RNA post-transcriptionally, affecting the stability of RNA and protein expression levels. This article delves into the latest advancements and challenges associated with various RNA modifications in prostate cancer tumor cells, tumor microenvironment, and core signaling molecule androgen receptors. It aims to provide new research targets and avenues for molecular diagnosis, treatment strategies, and improvement of the prognosis in prostate cancer.

Statin use and risk of bladder cancer: a meta-analysis.

PURPOSE: Emerging evidence suggests that statins may decrease the risk of cancers. However, available evidence on bladder cancer is conflicting. To quantify the association between statin use and risk of bladder cancer, we performed a detailed meta-analysis of published studies regarding this subject. METHODS: A literature search was carried out using MEDLINE, EMBASE, and OVID databases between January 1966 and October 2012. Before meta-analysis, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Fixed- and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95 % confidence intervals (CIs). Potential sources of heterogeneity were detected by meta-regression. Subgroup analyses, sensitivity analysis, and cumulative meta-analysis were also performed. RESULTS: A total of 13 (three RCTs, five cohort, and five case-control) studies contributed to the analysis. There was heterogeneity among the studies, but no publication bias. Pooled results indicated a nonsignificant increase in total bladder cancer risk among all statin users [RR = 1.07, 95 % CI (0.95, 1.21)]. Long-term statin use did not significantly affect the risk of total bladder cancer [RR = 1.21, 95 % CI (0.92, 1.59)]. In our subgroup analyses, the results were not substantially affected by study design, region, and confounder adjustment. Furthermore, sensitivity analysis confirmed the stability of the results. CONCLUSIONS: The findings of this meta-analysis suggested that there was no association between statin use and risk of bladder cancer. More studies, especially RCTs, are needed to confirm this association.

A comparative study of thulium laser resection of the prostate and bipolar transurethral plasmakinetic prostatectomy for treating benign prostatic hyperplasia.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Thulium laser is a new generation of surgical laser. It is a minimally invasive technology with several advantages, including rapid vaporization and minimal tissue damage and bleeding. However, details regarding the safety and efficacy of thulium laser in treating BPH remains unknown. We performed a comparative study in 100 patients with BPH of the safety and efficacy of thulium laser resection of the prostate (TMLRP, n = 50) and bipolar transurethral plasmakinetic prostatectomy (TUPKP, n = 50). We found that the efficacy and indications were the same in TMLRP and TUPKP. In TUPKP, the morbidity of urethrostenosis was low, and was nearly bloodless in surgery and had higher safety. Nevertheless, TUPKP is more suitable for patients with larger prostate volume. OBJECTIVE: To compare the safety and short-term efficacy of thulium laser resection of the prostate (TMLRP) and bipolar transurethral plasmakinetic prostatectomy (TUPKP) for the treatment of patients with benign prostatic hyperplasia (BPH). METHODS: A total of 100 patients diagnosed with BPH were randomly divided into two groups, treated with either TMLRP (50, group 1) or TUPKP (50, group 2). There was no significant difference in preoperative variables such as age, prostate volume, prostate-specific antigen (PSA) level, International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax ) and postvoid residual urine volume (PVR) between the two groups. The perioperative parameters and therapeutic effects were recorded and compared between the two groups. RESULTS: There were significant differences in the following parameters between the two groups (TMLRP vs TUPKP [mean ± SD]): operation duration, 61.2 ± 24.2 vs 30.14 ± 15.9 min; catheterization time, 1.8 ± 0.4 vs 3.2 ± 0.6 d; postoperative hospital stay, 3.3 ± 0.8 vs 4.1 ± 1.3 d. The volume of blood loss and postoperative bladder irrigation were significantly lower in TMLRP group than in the TUPKP group. At 1 month after the operation, there were four cases of urethral stricture in the TUPKP group. At 3 months after the operation, IPSS, quality of life (QoL), Qmax and PVR were significantly improved, with no significant difference between the two groups. CONCLUSIONS: TMLRP is superior to TUPKP in terms of safety, blood loss, recovery time and complication rate, and is as efficacious as TUPKP for treating BPH. Operation duration was significantly longer in the TMLRP group than in the TUPKP group.

Effect of tumor CD276 expression on infiltrating immune cells and clinicopathological features of prostate cancer.

BACKGROUND: Advanced prostate cancer (PCa) is often resistant to immunotherapy. In this study, we examined the role of CD276 in mediating immunotherapeutic effects through changes in immune cell infiltration. METHODS: Using transcriptomic and proteomic analyses, CD276 was identified as a potential target for immunotherapy. Subsequent in vivo and in vitro experiments confirmed its role as a potential mediator of immunotherapeutic effects. RESULTS: Multi-omic analysis suggested that CD276 was identified as a key molecule regulating the immune microenvironment (IM). In vivo experiments revealed that CD276 knockdown was found to enhance CD8+ T cell infiltration into the IM. Immunohistochemical analysis of PCa samples further confirmed the same findings. CONCLUSION: CD276 was found to inhibit the enrichment of CD8+ T cells in PCa. Thus, CD276 inhibitors may be potential targets for immunotherapy.

High level of circulating endothelial progenitor cells positively correlates with serum vascular endothelial growth factor in patients with renal cell carcinoma.

PURPOSE: Although accumulated evidence indicates that circulating endothelial progenitor cells contribute to tumor neovascularization, to our knowledge the level of these cells and its correlation with serum vascular endothelial growth factor in patients with renal cell carcinoma have not been studied. We measured this level and investigated its clinical significance in patients with renal cell carcinoma. MATERIALS AND METHODS: The level of circulating endothelial progenitor cells (percent of total peripheral blood mononuclear cells) was quantified by assaying the CD45(-)CD34(+)vascular endothelial growth factor receptor 2(+) cell phenotype in 53 patients with renal cell carcinoma, 33 with benign renal tumors and 40 healthy controls. Serum vascular endothelial growth factor was quantified. RESULTS: The mean circulating endothelial progenitor cell level in patients with renal cell carcinoma was 0.281%, significantly higher than in patients with benign renal tumors and healthy controls (0.073% and 0.076%, respectively, each p <0.001). Patients with stage III-IV renal cell carcinoma had a statistically higher level of these cells than those with stage I-II (0.339% vs 0.243%, p <0.001). The mean level in patients with renal cell carcinoma greater than 7 cm was 0.331%, significantly higher than in those with tumors 4 or less and 4 to 7 cm (0.225% and 0.231%, respectively, each p <0.001). Mean serum vascular endothelial growth factor in patients with renal cell carcinoma was higher than in patients with benign renal tumors and healthy controls (315.5 vs 34.6 and 26.9 pg/ml, respectively, each p <0.001). The preoperative circulating endothelial progenitor cell level positively correlated with serum vascular endothelial growth factor in patients with renal cell carcinoma (r = 0.710, p <0.001). Levels of these cells and of vascular endothelial growth factor significantly decreased postoperatively compared to preoperatively (0.081% vs 0.297% and 31.69 vs 310.70 pg/ml, respectively, each p <0.001). CONCLUSIONS: A high circulating endothelial progenitor cell level was found in patients with renal cell carcinoma, which positively correlated with serum vascular endothelial growth factor. Results support the potential use of circulating endothelial progenitor cells as a novel biomarker for renal cell carcinoma.

Efficacy of Transcutaneous Electrical Nerve Stimulation in the Management of Neurogenic Overactive Bladder: A Randomized Controlled Trial.

OBJECTIVE: The aim of the study was to investigate the therapeutic effect of transcutaneous electrical nerve stimulation on neurogenic overactive bladder that is refractory to pharmacotherapy. METHODS: This randomized trial recruited 83 participants with neurogenic overactive bladder that were nonresponsive to 3-mo first-line anticholinergic drug treatment. Participants were randomized into treatment and control groups. Transcutaneous electrical nerve stimulation current consisting of biphasic square wave with pulse durations of 150 µs and pulse frequency set at 20 Hz were applied to for 30 mins once a day for 90 days. Stimulation was provided over the lateral aspect of the sacrum bilaterally of the electrodes. Patients in the transcutaneous electrical nerve stimulation group stopped taking the anticholinergic drugs. The control group continued to receive anticholinergic drugs for 90 days. The participants' Overactive Bladder Symptom Score, the Medical Outcomes Study 36-Item Short-Form Health Survey scores, urodynamic values, and voiding diary data were assessed before and after the therapy. RESULTS: The transcutaneous electrical nerve stimulation treatment group had significantly decreased Overactive Bladder Symptom scores compared with the control group (P < 0.001); in addition, half of the Medical Outcomes Study 36-Item Short-Form Health Survey scores were significantly improved in the transcutaneous electrical nerve stimulation group (P < 0.05). The patients treated with transcutaneous electrical nerve stimulation improved significantly voiding diary parameters at P < 0.05. Similarly, urodynamic values at P < 0.05 favored the experimental group over the control group. CONCLUSIONS: Applying daily transcutaneous electrical nerve stimulation over the sacral region for 90 days to patient with neurogenic overactive bladder improved overactive bladder symptoms of patients whose response to anticholinergic drugs is far inferior. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Determine the therapeutic effect of transcutaneous electrical nerve stimulation (TENS) on neurogenic overactive bladder (NOAB); (2) Demonstrate the effectiveness of reflex suppression of the bladder using the TENS applied over the sacral region as a stimulation location; and (3) Confirm the TENS method using biphasic square waves with pulse durations of 150 µs and pulse frequencies of 20 Hz as applied is shown to be superior to anticholinergic drugs in managing NOAB. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The development and assessment of a predicting nomogram for the recovery of immediate urinary continence following laparoscopic radical prostatectomy.

Purpose: This study aimed to develop a nomogram to predict the recovery of immediate urinary continence in laparoscopic radical prostatectomy (LRP) patients. Methods: A prediction model was developed based on a dataset of 154 LRP patients. Immediate urinary continence was defined as free from using pads within 7 days after the removal of the urinary catheter. The least absolute shrinkage and selection operator regression (LASSO) model was applied to screen the features. Multivariate logistic regression analysis was used to establish prediction model integrating the features selected from the LASSO regression analysis. Receiver operating curve (ROC), calibration and decision curve analysis (DCA) were used to assess the model's discrimination, calibration and clinical utility. Results: The identified features of the prediction model included age, body mass index (BMI) and three pelvic anatomic parameters measured by MRI: membranous urethral length (MUL), intravesical prostatic protrusion length (IPPL) and puborectalis muscle width (PMW). The nomogram showed good discrimination with an are under the curve(AUC) of 0.914 (95% CI, 0.865-0.959, p < 0.001). Moreover, good calibration was showed in the model. Lastly, DCA showed that the nomogram was clinically useful. Conclusion: The developed novel nomogram that can predict the possibility for post-prostatectomy patients to recover immediate urinary continence could be used as a counseling tool to explain urinary incontinence to patients after LRP.

Erratum: Depletion of CDC5L inhibits bladder cancer tumorigenesis: Erratum.

[This corrects the article DOI: 10.7150/jca.32850.].

Combination of preoperative plasma fibrinogen and neutrophil-to-lymphocyte ratio to predict the prognosis for patients undergoing laparoscopic nephrectomy for renal cell carcinoma.

This study was conducted to investigate the prognostic significance of a combination of fibrinogen and neutrophil-to-lymphocyte ratio (NLR) named the F-NLR score as a novel indicator and further create nomograms for predicting the prognosis of patients with renal cell carcinoma (RCC) treated with laparoscopic nephrectomy. A total of 425 patients with RCC who underwent laparoscopic nephrectomy were included in this study. Then, we divided the patients based on the cut-off values of their F-NLR score into three categories: F-NLR 2 (both high fibrinogen and NLR), F-NLR 0 (both low fibrinogen and NLR), and F-NLR 1 (remaining patients). Cox regression analysis was performed to investigate the predictive performance of the F-NLR score on overall survival (OS) and cancer-specific survival (CSS). Predictive nomograms of F-NLR were established and internally validated. Time-dependent receiver operating characteristic (ROC) curve analysis was performed to assess the predictive accuracy of the nomogram, NLR, and fibrinogen as prognostic markers. The F-NLR 0, 1, and 2 groups included 226 (53.2%), 147 (34.6%), and 52 (12.2%) patients, respectively. Cox regression analysis showed that a high F-NLR score was significantly associated with poor prognosis and acted as an independent prognostic factor for OS and CSS (all P < 0.05). Predictive nomograms with F-NLR for OS (C-index: 0.773) and CSS (C-index: 0.838) were well developed. Time-dependent ROC results showed that nomograms containing F-NLR had better predictive performance than NLR and fibrinogen. F-NLR score was a novel effective prognostic biomarker for patients with RCC undergoing laparoscopic nephrectomy.

Extreme body mass index is associated with poor survival outcomes after radical cystectomy: a retrospective cohort study in a Chinese population.

BACKGROUND: Body mass index (BMI) has been evidenced to be a significant prognostic factor in multiple cancers. This retrospective study aimed to investigate the association between BMI and survival outcomes after radical cystectomy (RC) in patients with bladder cancer (BCa). METHODS: Clinical and pathological parameters of patients who were diagnosed with BCa and received RC between 2010 and 2018 were collected. The associations between BMI at surgery and clinicopathological features were examined. The prognostic value of BCa for overall survival (OS) and cancer-specific survival (CSS) was examined using the Kaplan-Meier method and Cox regression models. RESULTS: Among the 217 patients enrolled in this study, 13 (6.0%), 121 (55.8%), 60 (27.6%), and 23 (10.6%) had a BMI value of <18.5 kg/m2 (underweight), 18.5-23.9 kg/m2 (normal), 24-27.9 kg/m2 (overweight), and ≥28 kg/m2 (obese), respectively. Underweight and obese patients tended to have poorer survival after RC than normal and overweight patients (P<0.05). Multivariable Cox regression revealed that extreme BMI was an independent predictor of both OS (BMI <18.5 vs. 18.5-27.9 kg/m2, OR =2.675, 95% CI: 1.131-6.327, P=0.025; BMI ≥28 vs. 18.5-27.9 kg/m2, OR =3.693, 95% CI: 1.589-8.583, P=0.002) and CSS (BMI <18.5 vs. 18.5-27.9 kg/m2, OR =3.012, 95% CI: 1.180-7.687, P=0.021; BMI ≥28 vs. 18.5-27.9 kg/m2, OR =3.801, 95% CI: 1.526-9.469, P=0.004), along with tumor stage and urinary diversion type. CONCLUSIONS: Being underweight or obese is associated with a poor prognosis in patients with BCa undergoing RC. For patients who are preparing to undergo RC for BCa, controlling the BMI index through diet or exercise before surgery may contribute to the surgical curative effect and an improved prognosis.

ID2 Inhibits Bladder Cancer Progression and Metastasis via PI3K/AKT Signaling Pathway.

Background: Inhibitors of DNA-binding (ID) proteins are important regulators of cell proliferation and differentiation. The aim of this study was to evaluated the role of ID proteins in bladder cancer (BCa) and related molecular mechanisms. Methods: The TCGA database was analyzed for the expression and clinical significance of ID proteins. The expression of ID2 was determined by qRT-PCR, immunohistochemical staining and western blot. The role of ID2 was determined by CCK-8, colony formation, wound healing, transwell and xenograft tumor assays, and the potential mechanism of ID2 in BCa was investigated by RNA sequencing. Results: ID2 expression was significantly downregulated in TCGA database and clinical samples, and high ID2 expression was associated with low-grade tumor staging and correlated with better overall survival, disease specific survival (DSS) and progress free interval (PFI). In vivo and in vitro experiments showed that knockdown of ID2 promoted proliferation, migration, invasion and metastasis of BCa cells, while overexpression of ID2 significantly inhibited cell proliferation, migration, invasion and metastasis. Mechanistically, ID2 acts as a tumor suppressor through PI3K/AKT signaling pathway to inhibit the progression and metastasis of BCa. Conclusion: Our results suggest that ID2 exerts tumor suppressive effects in BCa through PI3K/AKT signaling pathway, and altered ID2 expression can be used as a biomarker of BCa progression and metastasis.

Relationship between urine specific gravity and the prevalence rate of kidney stone.

BACKGROUND: The purpose of this study was to evaluate the relationship between urine specific gravity (USG) and the prevalence rate of kidney stone. METHODS: We conducted a cross-sectional study of adult participants (≥20 years) of the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2008. The USG was divided into three groups: <1.008, 1.008-1.020 and >1.020. Univariate and multivariate logistic regression analysis was used to determine the effect of USG on the prevalence rate of kidney stone. RESULTS: A total of 4,791 patients were included in this study, of which 464 (9.7%) reported a history of kidney stone. Univariate logistic regression analysis showed that age, gender, race, hypertension, diabetes, body mass index (BMI), estimated glomerular filtration rate (eGFR), USG and urine creatinine were closely related to the prevalence of kidney stones. After adjusting for known confounding factors, multivariate logistic regression showed that the prevalence rate of kidney stone increased with the increase of USG (1.008-1.020 vs. <1.008, OR =1.31, 95% CI, 0.09-1.91, P=0.155; >1.020 vs. <1.008, OR =1.71, 95% CI, 1.16-2.54, P=0.007). CONCLUSIONS: The increase of USG was significantly correlated with self-reported kidney stone. This finding helps to identify risk factors for kidney stones as early as possible in the United States.

Development of nomograms related to inflammatory biomarkers to estimate the prognosis of bladder cancer after radical cystectomy.

BACKGROUND: Bladder cancer is one of the most common carcinomas and it brings about huge social economic burden. There is not a reliable way to predict the prognosis of bladder patients. We develop the nomogram to predict the prognosis of bladder cancer patients. METHODS: A total of 127 bladder cancer patients after radical cystectomy were studied retrospectively. Their clinicopathological data were collected for statistical analysis. RESULTS: The level of albumin/globulin ratio (AGR), C-reactive protein/albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) associated with pathological and hematological parameters like T stage and hemoglobin. Furthermore, the AGR was associated with overall survival (OS) and CAR, NLR, and PLR were associated with both OS and progression-free survival (PFS) (P<0.05). The multivariate analysis revealed that tobacco smoking, tumor T stage, M stage, NLR, CAR, and AGR were all independent predictors for OS of patients and tobacco smoking, tumor T stage, NLR, CAR, and AGR were independent predictors for PFS of patients. In addition, AGR, CAR, and NLR, as well as, the clinicopathological parameters in the development of nomograms with a C index of 0.901 (95% CI: 0.505-1.269) for OS, and 0.807 (95% CI: 0.755-0.858) for PFS. The nomograms were able to provide a prognosis of the OS with the area under the curve (AUC) =0.86. Further, tests assessed the PFS with the AUC =0.84. CONCLUSIONS: This study demonstrates that the nomograms of the inflammatory biomarkers were able to predict prognosis of bladder cancer patients after radical cystectomy.

Long Noncoding RNA SNHG1 Activates Autophagy and Promotes Cell Invasion in Bladder Cancer.

LncRNAs play important roles in bladder cancer. However, only a few studies report on the correlation between lncRNAs expression and autophagy in bladder cancer. This study aimed to explore the effect of lncRNA on autophagy in bladder cancer. The findings showed high expression of SNHG1 in the bladder cancer cells and tumor tissues. The high expression of SNHG1 was positively correlated with bladder cancer cell invasion, proliferation, and autophagy. This finding implies that SNHG1 promotes bladder cancer cell invasion and proliferation via autophagy. Further analysis of the mechanism of action of SNHG1 showed that it functions as a sponge of miRNA-493 in bladder cancer. miRNA-493 binds on the 3' -UTR of ATG14 mRNA thus affecting ATG14 protein expression, which is implicated in autophagy. These findings are supported by previous preclinical studies using multiple Bca cell lines and TCGA, which demonstrate that SNHG1 plays an oncogenic role by acting as a sponge of miR-493-5p or as its ceRNA. Upregulation of SNHG1 promotes proliferation, invasion, and autophagy of bladder cancer cells through the miR-493-5p/ATG14/autophagy pathway. Therefore, SNHG1 may act as a potential therapeutic target for the treatment of bladder cancer.

Combination of Total Psoas Index and Albumin-Globulin Score for the Prognosis Prediction of Bladder Cancer Patients After Radical Cystectomy: A Population-Based Study.

BACKGROUND: Sarcopenia as the loss of skeletal muscle mass is related with poor postoperative survival. This work purposed to evaluate the prognostic prediction of the total psoas index (TPI), albumin-globulin score (AGS), and the combination of TPI and AGS (CTA) in bladder cancer (BCa) patients after radical cystectomy. METHODS: BCa patients that received radical cystectomy between 2012 and 2020 were retrieved from our medical center. The calculation of TPI was based on the plain computed tomography images. The predictive effects of TPI, AGS, and CTA grade on survival of BCa patients were analyzed and compared with the albumin-globulin ratio (AGR) through the receiver operating characteristic (ROC) curves. A nomogram was further established based on the Cox regression results from CTA grade and clinicopathological characteristics, which are verified by the decision curve analysis (DCA). RESULTS: A total of 112 eligible patients diagnosed as BCa were included in this study for retrospective analysis. The patients with lower TPI or higher AGS grade (1/2) contained poorer overall survival (OS) and disease-free survival (DFS). Divided by CTA grade, there were 35 (31.25%) patients in grade 1 associated with the best postoperative prognosis, which was accompanied with increased TPI and decreased AGS. The CTA grade could better predict postoperative outcomes compared with TPI, AGR, and AGS for the highest area under the curve (AUC; 0.674 of OS and 0.681 of DFS). The 3- and 5-year OS and DFS nomograms were conducted based on CTA grade and clinical variables, with a higher predictive performance than the TNM stage. CONCLUSION: This study revealed that the novel index CTA functioned as an effective prognostic predictor for postoperative OS and DFS of BCa patients after radical cystectomy. Preoperative assessment of CTA would contribute to optimizing clinical therapies.