The causal association between smoking, alcohol consumption and risk of bladder cancer: A univariable and multivariable Mendelian randomization study.

Smoking and alcohol consumption are associated with bladder cancer risk in observational studies. We conducted a two-sample univariable and multivariable Mendelian randomization (MR) analysis to determine whether those associations are causal. We used 21, 126, 360, 39 single nucleotide polymorphisms (SNPs) as instrumental variables for number of cigarettes per day, lifetime smoking index, smoking initiation, and drinks per week, respectively. A total of 1115 cases with bladder cancer and 174 006 noncases from FinnGen consortium and 2883 cases with bladder cancer and 417 955 noncases from UK Biobank study were obtained. Genetic predisposition to cigarettes per day, lifetime smoking index and smoking initiation were positively associated with an increased risk of bladder cancer in both the FinnGen and UK Biobank consortium. The summary odds ratio (OR) of bladder cancer was 1.79 (95% confidence interval [CI], 1.31-2.45; P = .0002), 2.38 (95% CI, 1.45-3.88; P = .0005) and 1.91 (95% CI, 1.46-2.50; P = 1.59 × 10-06 ) for one SD increase in the number of cigarettes per day, lifetime smoking index and smoking initiation, respectively. The genetically instrumented number of drinks per week was not associated with bladder cancer (OR = 0.69; 95% CI, 0.44-1.10; P = .1237). Estimates were consistent in multivariable MR analyses by the adjustments of body mass index and education. Our study suggests a causal potential of the association of smoking but not alcohol consumption with bladder cancer according to current evidence.

Spatial and temporal patterns of prostate cancer burden and their association with Socio-Demographic Index in Asia, 1990-2019.

BACKGROUND: Prostate cancer is the second most frequently diagnosed cancer for males worldwide, but the spatial and temporal trends of prostate cancer burden remain unknown in Asia. This study aimed to investigate the changing spatial and temporal trends of incidence, prevalence, mortality, disability-adjusted life year (DALY), and mortality-to-incidence ratio (MIR) of prostate cancer, and their association with the Socio-Demographic Index (SDI) in 48 Asian countries from 1990 to 2019. METHODS: Data were extracted from the Global Health Data Exchange query tool, covering 48 Asian countries from 1990 to 2019. The average annual percent change was calculated to evaluate temporal trends. Spatial autocorrelation analysis was used to obtain spatial patterns, and the association between SDI and prostate cancer burden was estimated using a spatial panel model. RESULTS: In Asia, the age-standardized incidence and prevalence of prostate cancer increased in almost all countries, and its mortality and DALY also increased in over half of the countries. Significantly regional disparities were found in Asia, and the hot spots for incidence, prevalence, mortality, and DALY were all located in Western Asia, the hot spots of percent change also occurred in Western Asia for incidence and DALY. Furthermore, SDI had a positive association with mortality (coef = 2.51, 95% confidence interval [CI]: 2.13-2.90) and negative association with DALY (coef = -14.99, 95% CI: -20.37 to -9.60) and MIR (coef = -0.95, 95%CI: -0.99 to -0.92). CONCLUSIONS: Prostate cancer burden increased rapidly throughout Asia and substantial disparities had persisted between countries. Geographically targeted interventions are needed to reduce the prostate cancer burden throughout Asia and in specific countries.

Circ-sirt1 inhibits growth and invasion of gastric cancer by sponging miR-132-3p/miR-212-3p and upregulating sirt1 expression.

circRNAs have been considered as a rising factor in cancers. However, the roles and mechanisms of circ-sirt1 in gastric cancer (GC) remain largely unknown. In this study, we found that the expressions of sirt1 and circ-sirt1 are decreased in tissues or serums of GC patients by real-time quantitative PCR (RT-qPCR). The expressions of miR-132-3p/miR-212-3p showed an opposite tendency in these samples. The co-transfection of miR-132-3p/miR-212-3p mimics counteracted the enhancement of sirt1 expression induced by circ-sirt1. The results of cell colony-formation assay and transwell assays demonstrated that the proliferation, migration, and invasion activities of BGC-823 cells were inhibited by circ-sirt1 overexpression or miR-132-3p/miR-212-3p knockdown, respectively. The xenograft tumor model result indicated that the circ-sirt1 overexpression suppressed the tumor growth of BGC-823 cells. The regulation of miR-132-3p/miR-212-3p between circ-sirt1 and sirt1 was verified in the mice tumor tissues. Thus, circ-sirt1 inhibited tumor growth and invasion probably by sponging miR-132-3p/miR-212-3p and upregulating sirt1 expression in GC. These findings may provide a theoretical basis for the classification of GC and a novel therapeutic target for GC patients.

circ-Sirt1 controls NF-κB activation via sequence-specific interaction and enhancement of SIRT1 expression by binding to miR-132/212 in vascular smooth muscle cells.

NF-κB-mediated inflammatory phenotypic switching of vascular smooth muscle cells (VSMCs) plays a central role in atherosclerosis and neointimal formation. However, little is known about the roles of circRNAs in the regulation of NF-κB signaling. Here, we identify the involvement of circ-Sirt1 that was one of transcripts of SIRT1 host gene in VSMC inflammatory response and neointimal hyperplasia. First, in the cytoplasm, circ-Sirt1 directly interacts with and sequesters NF-κB p65 from nuclear translocation induced by TNF-α in a sequence-dependent manner. The inhibitory complex of circ-Sirt1-NF-κB p65 is not dependent on IκBα. Second, circ-Sirt1 binds to miR-132/212 that interferes with SIRT1 mRNA, and facilitates the expression of host gene SIRT1. Increased SIRT1 results in deacetylation and inactivation of the nuclear NF-κB p65. These findings illustrate that circ-Sirt1 is a novel non-coding RNA regulator of VSMC phenotype.

Effect of electrode temperature on measurements of transcutaneous carbon dioxide partial pressure and oxygen partial pressure in very low birth weight infants. / 电极温度对极低出生体重儿经皮二氧化碳分压和氧分压监测的影响.

OBJECTIVES: To evaluate the accuracy and safety of measurements of transcutaneous carbon dioxide partial pressure (TcPCO2) and transcutaneous oxygen partial pressure (TcPO2) at electrode temperatures lower than the value used in clinical practice in very low birth weight infants. METHODS: A total of 45 very low birth weight infants were enrolled. TcPCO2 and TcPO2 measurements were performed in these infants. Two transcutaneous monitors were placed simultaneously for each subject. One electrode was set and maintained at 42℃ used in clinical practice for neonates (control group), and the other was successively set at 38℃, 39℃, 40°C, and 41℃ (experimental group). The paired t-test was used to compare the measurement results between the groups. A Pearson correlation analysis was used to analyze the correlation between the measurement results of the experimental group and control group, and between the measurement results of experimental group and arterial blood gas parameters. RESULTS: There was no significant difference in TcPCO2 between each experimental subgroup (38-41℃) and the control group. TcPCO2 in each experimental subgroup (38-41℃) was strongly positively correlated with TcPCO2 in the control group (r>0.9, P<0.05) and arterial carbon dioxide partial pressure (r>0.8, P<0.05). There were significant differences in TcPO2 between each experimental subgroup (38-41℃) and the control group (P<0.05), but TcPO2 in each experimental subgroup (38-41℃) was positively correlated with TcPO2 in the control group (r=0.493-0.574, P<0.05) and arterial oxygen partial pressure (r=0.324-0.399, P<0.05). No skin injury occurred during transcutaneous measurements at all electrode temperatures. CONCLUSIONS: Lower electrode temperatures (38-41℃) can accurately measure blood carbon dioxide partial pressure in very low birth weight infants, and thus can be used to replace the electrode temperature of 42°C. Transcutaneous measurements at the lower electrode temperatures may be helpful for understanding the changing trend of blood oxygen partial pressure.

Nomogram for predicting the survival of gastric adenocarcinoma patients who receive surgery and chemotherapy.

BACKGROUND: Surgery is the only way to cure gastric adenocarcinoma (GAC), and chemotherapy is the basic adjuvant management for GAC. A significant prognostic nomogram for predicting the respective disease-specific survival (DSS) rates of GAC patients who receive surgery and chemotherapy has not been established. OBJECTIVE: We were planning to establish a survival nomogram model for GAC patients who receive surgery and chemotherapy. METHODS: We identified 5764 GAC patients who had received surgery and chemotherapy from the record of Surveillance, Epidemiology, and End Results (SEER) database. About 70% (n = 4034) of the chosen GAC patients were randomly assigned to the training set, and the rest of the included ones (n = 1729) were assigned to the external validation set. A prognostic nomogram was constructed by the training set and the predictive accuracy of it was validated by the validation set. RESULTS: Based on the outcome of a multivariate analysis of candidate factors, a nomogram was developed that encompassed age at diagnosis, number of regional lymph nodes examined after surgery, number of positive regional lymph nodes, sex, race, grade, derived AJCC stage, summary stage, and radiotherapy status. The C-index (Harrell's concordance index) of the nomogram model was some larger than that of the traditional seventh AJCC staging system (0.707 vs 0.661). Calibration plots of the constructed nomogram displayed that the probability of DSS commendably accord with the survival rate. Integrated discrimination improvement (IDI) revealed obvious increase and categorical net reclassification improvement (NRI) showed visible enhancement. IDI for 3-, 5- and 10- year DSS were 0.058, 0.059 and 0.058, respectively (P > 0.05), and NRI for 3-, 5- and 10- year DSS were 0.380 (95% CI = 0.316-0.470), 0.407 (95% CI = 0.350-0.505), and 0.413 (95% CI = 0.336-0.519), respectively. Decision curve analysis (DCA) proved that the constructed nomogram was preferable to the AJCC staging system. CONCLUSION: The constructed nomogram supplies more credible DSS predictions for GAC patients who receive surgery and chemotherapy in the general population. According to validation, the new nomogram will be beneficial in facilitating individualized survival predictions and useful when performing clinical decision-making for GAC patients who receive surgery and chemotherapy.

Clinical Significance of TRMT6 in Hepatocellular Carcinoma: A Bioinformatics-Based Study.

BACKGROUND The purpose of this study was to investigate the correlation between TRMT6 mRNA expression levels and clinicopathological features in primary HCC patients and to evaluate their prognostic value. MATERIAL AND METHODS The clinical information and the mRNA sequencing data of the patients with primary hepatocellular carcinoma (HCC) were extracted from The Cancer Genome Atlas (TCGA) Liver Cancer database. The correlation between the clinicopathological features and the expression of TRMT6 was analyzed by t test and chi-square test. The overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method and Cox regression models. Gene set enrichment analysis (GSEA) was used to explore the potential mechanisms of TRMT6 dysregulation in primary HCC patients. RESULTS Compared to normal tissues, TRMT6 was significantly upregulated in primary HCC tissues. Kaplan-Meier survival curves revealed that higher TRMT6 expression was associated with reduced RFS (p=0.0146) and OS (p=0.0224) in HCC patients. Moreover, multivariable Cox regression analysis indicated that TRMT6 upregulation independently predicted poor RFS (HR: 1.871, 95% CI: 1.204, 2.905, p=0.005) and OS (HR: 2.176, 95% CI: 1.234, 3.836, p=0.007). Gene Set Enrichment Analysis (GSEA) indicated that primary HCC samples in the TRMT6 high expression group were enriched for the G2M checkpoint, spermatogenesis, and MYC target genes. CONCLUSIONS TRMT6 was upregulated in HCC tissues, and higher TRMT6 expression levels was correlated with reduced OS and RFS in patients with primary HCC. TRMT6 might be a promising prognostic biomarker for poor clinical outcomes in primary HCC patients.

Actinin-4 as a Diagnostic Biomarker in Serum of Breast Cancer Patients.

BACKGROUND alpha-actinin-4 (Actinin-4 or ACTN4), originally identified as an actin-binding protein associated with the biological function of cancer cells, appears to be highly expressed in numerous human epithelial carcinomas, including breast cancer (BC). In the present study we assessed the role of serum ACTN4 as a biomarker for BC diagnosis, as well as the association between ACTN4 levels and clinicopathological features. MATERIAL AND METHODS ACTN4 expression level was measured with quantitative real-time PCR (qRT-PCR) analysis in serum specimens of 128 BC patients and 96 healthy volunteers. χ² testing was conducted to explore the association of ACTN4 levels with clinicopathologic factors. Moreover, the diagnostic value of ACTN4 was analyzed using receiver operating characteristic (ROC) curves. RESULTS Serum ACTN4 level was obviously upregulated in patients with BC compared with healthy controls (P<0.05). High ACTN4 expression was significantly associated with clinical stage (P=0.000), tumor grade (P=0.004), and lymph node status (P=0.024). However, no association was found between ACTN4 expression and age, tumor size, ER status, PR status, or HER-2 status (all P>0.05). The ROC analysis showed that the area under the curve (AUC) of ACTN4 was 0.887 (95%CI: 0.843-0.931), with sensitivity of 80.5% and specificity of 84.4%, and the cutoff value was 1.050. CONCLUSIONS ACTN4 in serum can serve as a clinical predictor in the diagnosis or prediction of clinical outcomes of patients with BC.

Up-Regulation of Phosphatase in Regenerating Liver-3 (PRL-3) Contributes to Malignant Progression of Hepatocellular Carcinoma by Activating Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN)/Phosphoinositide 3-Kinase (PI3K)/AKT Signaling Pathway.

BACKGROUND The purpose of the study was to investigate the functional roles of phosphatase in regenerating liver-3 (PRL-3) in hepatocellular carcinoma (HCC), as well as the related molecular mechanisms. MATERIAL AND METHODS HCC tissues and adjacent normal tissues were collected from 124 HCC patients. The mRNA and protein levels of PRL-3 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays, respectively. The relationship between PRL-3 expression and clinical characteristics of HCC patients was evaluated by chi-square test. MTT and Transwell assays were performed to estimate cell proliferation and motility, respectively. RESULTS The expression of PRL-3 was significantly increased in HCC tissues and cells at both protein and mRNA levels (P<0.01 for all). Furthermore, the up-regulation of PRL-3 was positively correlated with hepatic vascular invasion (P=0.019), lymph node metastasis (P=0.012), and TNM stage (P=0.001). The knockdown of PRL-3 suppressed HCC cell proliferation, migration, and invasion, and PR3K/AKT pathway activity was also obviously inhibited in HCC cells with PRL-3 deficiency. The levels of PTEN were negatively associated with PRL-3 expression. PRL-3 might inhibit the protein level of PTEN through enhancing its phosphorylation level. The transfection of si-PTEN can reverse the anti-tumor action caused by PRL-3 knockdown in HCC cells. CONCLUSIONS Up-regulation of PRL-3 may activate the PI3K/AKT signaling pathway and enhance malignant progression of HCC through targeting PTEN.

Transparent ultraviolet photovoltaic cells.

Photovoltaic cells have been fabricated from p-GaN/MgO/n-ZnO structures. The photovoltaic cells are transparent to visible light and can transform ultraviolet irradiation into electrical signals. The efficiency of the photovoltaic cells is 0.025% under simulated AM 1.5 illumination conditions, while it can reach 0.46% under UV illumination. By connecting several such photovoltaic cells in a series, light-emitting devices can be lighting. The photovoltaic cells reported in this Letter may promise the applications in glass of buildings to prevent UV irradiation and produce power for household appliances in the future.

Improved performance of ZnO light-emitting devices by introducing a hole-injection layer.

ZnO p-n homojunction light-emitting devices (LEDs) have been fabricated, and by introducing a p-type GaN as the hole-injection layer, the output power of the LEDs can reach 18.5 µW when the drive current is 60 mA, which is almost three orders of magnitude larger than the pristine LEDs without the hole-injection layer. The improved performance can be attributed to the extra holes injected into the p-ZnO layer from the p-GaN hole-injection layer.

Autophagy-related long non-coding RNAs act as prognostic biomarkers and associate with tumor microenvironment in prostate cancer.

Aberrant autophagy could promote cancer cells to survive and proliferate in prostate cancer (PCa). LncRNAs play key roles in autophagy regulatory network. We established a prognostic model, which autophagy-related lncRNAs (au-lncRNAs) were used as biomarkers to predict prognosis of individuals with PCa. Depending on au-lncRNAs from the Cancer Genome Atlas and the Human Autophagy Database, a risk score model was created. To evaluate the prediction accuracy, the calibration, Kaplan-Meier, and receiver operating characteristic curves were used. To clarify the biological function, gene set enrichment analyses (GSEA) were performed. Quantitative real-time PCR (qRT-PCR) was employed to determine the au-lncRNAs expression in PCa cell lines and healthy prostate cells for further confirmation. We identified five au-lncRNAs with prognostic significance (AC068580.6, AF131215.2, LINC00996, LINC01125 and LINC01547). The development of a risk scoring model required the utilization of multivariate Cox analysis. According to the model, we categorized PCa individuals into low- and high-risk cohorts. PCa subjects in the high-risk group had a worse disease-free survival rate than those in the low-risk group. The 1-, 3-, and 5-year periods had corresponding areas under curves (AUC) of 0.788, 0.794, and 0.818. The prognosis of individuals with PCa could be predicted by the model with accuracy. Further analysis with GSEA showed that the prognostic model was associated with the tumor microenvironment, including immunotherapy, cancer-related inflammation, and metabolic reprogramming. Four lncRNAs expression in PCa cell lines was greater than that in healthy prostate cells. The au-lncRNA prognostic model has significant clinical implications in prognosis of PCa patient.

Clinical biomarker-based biological aging and risk of benign prostatic hyperplasia: A large prospective cohort study.

Objective: Chronological age (CAge), biological age (BAge), and accelerated age (AAge) are all important for aging-related diseases. CAge is a known risk factor for benign prostatic hyperplasia (BPH); However, the evidence of association of BAge and AAge with BPH is limited. This study aimed to evaluate the association of CAge, Bage, and AAge with BPH in a large prospective cohort. Method: A total of 135,933 males without BPH at enrolment were extracted from the UK biobank. We calculated three BAge measures (Klemera-Doubal method, KDM; PhenoAge; homeostatic dysregulation, HD) based on 16 biomarkers. Additionally, we calculated KDM-BAge and PhenoAge-BAge measures based on the Levine method. The KDM-AAge and PhenoAge-AAge were assessed by the difference between CAge and BAge and were standardized (mean = 0 and standard deviation [SD] = 1). Cox proportional hazard models were applied to assess the associations of CAge, Bage, and AAge with incident BPH risk. Results: During a median follow-up of 13.150 years, 11,811 (8.690%) incident BPH were identified. Advanced CAge and BAge measures were associated with an increased risk of BPH, showing threshold effects at a later age (all P for nonlinearity <0.001). Nonlinear relationships between AAge measures and risk of BPH were also found for KDM-AAge (P = 0.041) and PhenoAge-AAge (P = 0.020). Compared to the balance comparison group (-1 SD < AAge < 1 SD), the accelerated aging group (AAge > 2 SD) had a significantly elevated BPH risk with hazard ratio (HR) of 1.115 (95% CI, 1.000-1.223) for KDM-AAge and 1.180 (95% CI, 1.068-1.303) for PhenoAge-AAge, respectively. For PhenoAge-AAge, subgroup analysis of the accelerated aging group showed an increased HR of 1.904 (95% CI, 1.374-2.639) in males with CAge <50 years and 1.233 (95% CI, 1.088-1.397) in those having testosterone levels <12 nmol/L. Moreover, AAge-associated risk of BPH was independent of and additive to genetic risk. Conclusions: Biological aging is an independent and modifiable risk factor for BPH. We suggest performing active health interventions to slow biological aging, which will help mitigate the progression of prostate aging and further reduce the burden of BPH.

MgZnO p-n heterostructure light-emitting devices.

MgZnO heterostructure light-emitting devices (LEDs) have been fabricated from p-Mg(0.35)Zn(0.65)O/n-Mg(0.20)Zn(0.80)O structures, and the p-type Mg(0.35)Zn(0.65)O film was realized using a lithium-nitrogen codoping method. Obvious ultraviolet emission peaked at around 355 nm dominates the electroluminescence (EL) spectra of the device at room temperature, which comes from the near-band-edge emission of the n-type Mg(0.20)Zn(0.80)O film. This is the first report on MgZnO heterostructured LEDs and the shortest EL emission ever reported in ZnO-based p-n junction LEDs to the best of our knowledge.

Identification of the MALAT1/miR-106a-5p/ZNF148 feedback loop in regulating HaCaT cell proliferation, migration and apoptosis.

Aims: This study aims to investigate the function of positive feedback loops involving noncoding RNA in diabetic wound healing. Methods: We developed a mouse diabetic wound model to confirm that hyperglycemia can impair wound healing. We also used an in vitro keratinocyte model in high-glucose conditions to investigate the mechanism of delayed wound healing. Results: MALAT1 was decreased in diabetic mouse wound tissue and can promote keratinocyte biological functions. MALAT1 could bind to miR-106a-5p to modulate the expression of ZNF148, a target gene of miR-106a-5p. Surprisingly, ZNF148 bound to a region in the MALAT1 promoter to stimulate gene expression. Conclusion: ZNF148-activated MALAT1 increases ZNF148 expression by competitively binding miR-106a-3p, generating a positive feedback loop that enhances keratinocyte function.

Delayed wound repair is a leading cause of diabetic foot ulcers. However, the molecular mechanism underlying impaired wound healing in diabetes is unclear. In our study we found that a positive feedback loop consisting of MALAT1, miR-106a-5p and ZNF148 could promote chronic wound repair. In diabetic skin tissues, MALAT1 levels were lower, causing impairments in skin cell function. On a molecular level, MALAT1 can bind miR-106a-5p to increase ZNF148 levels. Surprisingly, ZNF148 can bind the promoter of MALAT1 to reverse the decline of MALAT1 levels in diabetic wounds. Our findings advance our understanding of chronic diabetic wounds and, more crucially, open new therapeutic possibilities for this disease.

Ten interleukins and risk of prostate cancer.

Background: Interleukins (ILs) have been reported to be related to prostate cancer. The aims of this study were to estimate the levels for several key interleukins in prostate cancer and the causal effects between them. Methods: We conducted a bi-directional two-sample Mendelian randomization (MR) study to assess the causal associations between ILs and prostate cancer. Genetic instruments and summary-level data for 10 ILs were obtained from three genome-wide association meta-analyses. Prostate cancer related data were obtained from the PRACTICAL (79,148 cases and 61,106 controls), UK Biobank (7,691 cases and 169,762 controls) and FinnGen consortium (10,414 cases and 124,994 controls), respectively. Results: The odds ratio of prostate cancer was 0.92 (95% confidence interval (CI), 0.89, 0.96; P=1.58×10-05) and 1.12 (95% CI, 1.07, 1.17; P=6.61×10-07) for one standard deviation increase in genetically predicted IL-1ra and IL-6 levels, respectively. Genetically predicted levels of IL-1ß, IL-2a, IL-6ra, IL-8, IL-16, IL-17, IL-18, and IL-27 were not associated with the risk of prostate cancer. Reverse MR analysis did not find the associations between genetic liability to prostate cancer and higher levels of IL-1ra (ß, -0.005; 95% CI, -0.010, 0.001; P=0.111) and IL-6 (ß, 0.002; 95% CI, -0.011, 0.014; P=0.755). Conclusion: This MR study suggests that long-term IL-6 may increase the risk of prostate cancer and IL-1ra may reduce it.

Using Haemocoagulase Agkistrodon in Patients Undergoing Transurethral Plasmakinetic Resection of the Prostate: A Pilot, Real-World, and Propensity Score-Matched Study.

Objectives: To compare the clinical outcomes of using different hemostatic agents after transurethral plasmakinetic resection of the prostate (TUPKP) in benign prostatic hyperplasia (BPH) patients. Methods: The patients were divided into 5 groups according to the hemostatic agents used after TUPKP, including the haemocoagulase agkistrodon for injection (HCA), hemocoagulase for injection (HC), hemocoagulase bothrops atrox for injection (HCB), ethylenediamine diaceturate injection (EDD), and tranexamic acid (TXA). Propensity score matching was performed based on age, body mass index, prostate volume, hypertension status, fasting blood glucose, smoking, and drinking history. The hospitalization time, bladder irrigation time, indwelling catheterization time, the patency of urine flow, and blood transfusion records were used as outcome indicators to compare the clinical effects of these five agents. Results: We finally matched 65 pairs receiving HCA or HC, 71 pairs receiving HCA or HCB, 38 pairs receiving HCA or TXA, and 29 pairs receiving HCA or EDD. Compared with HC, HCA given during the perioperative period significantly reduced the median hospitalization time [7.00 days (5.00, 8.00) vs. 9.00 days (8.00, 10.00); p < 0.001] and median catheterization time (109.00 hours [88.00, 129.00] vs. 164.00 hours [114.00, 189.00], p < 0.001). Compared with EDD, the median hospitalization time (7.00 days [6.00, 8.00] vs. 10.00 days [8.00, 11.00]; p < 0.001) and median catheterization time (113.00 hours [95.00, 143.00] vs. 160.00 hours [139.00, 168.00]; p < 0.001) were also significant shorter in HCA group. Compared with HCB, median bladder irrigation time (45.00 hours [27.00, 71.00] vs. 49.00 hours [45.00, 72.00]; p = 0.04) was shorter in the HCA group. However, there were no statistical differences in outcomes between HCA and TXA. Conclusions: HCA probably has an advantage over HC, HCB, and EDD in reducing the hospitalization time, catheterization time, and bladder irrigation time among BPH patients undergoing TUPKP.

Coffee and caffeine consumption and risk of renal cell carcinoma: A Mendelian randomization study.

Background: The association between coffee and caffeine consumption and the risk of renal cell carcinoma was inconsistent among observational studies, and whether these observed associations were causal remained unclear. Therefore, we performed two-sample Mendelian randomization (MR) study to assess the causal nature of the association. Materials and methods: In this study, 12 and two independent single nucleotide polymorphisms (SNPs) related to coffee and caffeine consumption at a genome-wide significance level of p < 5 × 10-8 were used as instrumental variables (IVs), respectively. Summary-level data for renal cell carcinoma were taken from the FinnGen consortium with up to 174,977 individuals, and the International Agency for Research on Cancer (IARC) with 13,230 individuals. We used inverse-variance weighted (IVW) as the main method, followed by the weighted median method, the MR-Egger regression method, and the MR robust adjusted profile score method. Outlier and pleiotropic variants were assessed by the MR Pleiotropy RESidual Sum and Outlier test and MR-Egger regression. We used meta-analysis methods in fixed-effects to combine the estimates from the two sources. Results: The genetically predicted coffee consumption was not associated with the risk of renal cell carcinoma in the FinnGen consortium, and the relationship was consistent in the IARC consortium. The pooled odds ratio (OR) per 50% increase of coffee consumption was 0.752 [95% confidence interval (CI), 0.512-1.105; p = 0.147]. In addition, complementary analyses that separated the coffee-related SNPs according to their relationship with blood levels of caffeine metabolites (higher, lower, or unrelated) found no relationship with renal cell carcinoma. The results were consistent after excluding eight SNPs due to potential risk factors at genome-wide significance (p < 5 × 10-8). Moreover, genetically predicted per 80-mg increase in caffeine consumption was not associated with the risk of renal cell carcinoma (pooled OR = 0.872, 95% CI: 0.676-1.125, p = 0.292). Conclusion: Our MR study provided no convincing evidence for a causal effect between coffee and caffeine consumption and the risk of renal cell carcinoma. The associations for renal cell carcinoma need to be verified in well-powered studies.

Oral microbiota in the oral-genitourinary axis: identifying periodontitis as a potential risk of genitourinary cancers.

Periodontitis has been proposed as a novel risk factor of genitourinary cancers: although periodontitis and genitourinary cancers are two totally distinct types of disorders, epidemiological and clinical studies, have established associations between them. Dysbiosis of oral microbiota has already been established as a major factor contributing to periodontitis. Recent emerging epidemiological evidence and the detection of oral microbiota in genitourinary organs indicate the presence of an oral-genitourinary axis and oral microbiota may be involved in the pathogenesis of genitourinary cancers. Therefore, oral microbiota provides the bridge between periodontitis and genitourinary cancers. We have carried out this narrative review which summarizes epidemiological studies exploring the association between periodontitis and genitourinary cancers. We have also highlighted the current evidence demonstrating the capacity of oral microbiota to regulate almost all hallmarks of cancer, and proposed the potential mechanisms of oral microbiota in the development of genitourinary cancers.

Ligand-Based and Docking-Based Virtual Screening of MDM2 Inhibitors as Potent Anticancer Agents.

A ligand-based and docking-based virtual screening was carried out to identify novel MDM2 inhibitors. A pharmacophore model with four features was used for virtual screening, followed by molecular docking. Seventeen compounds were selected for an in vitro MDM2 inhibition assay, and compounds AO-476/43250177, AG-690/37072075, AK-968/15254441, AO-022/43452814, and AF-399/25108021 showed promising MDM2 inhibition activities with K i values of 9.5, 8.5, 23.4, 3.2, and 23.1 µM, respectively. Four compounds also showed antiproliferative activity, and compound AO-022/43452814 was the most potent hit with IC50 values of 19.35, 26.73, 12.63, and 24.14 µM against MCF7 (p53 +/+), MCF7 (p53 -/-), HCT116 (p53 +/+), and HCT116 (p53 -/-) cell lines, respectively. Compound AO-022/43452814 could be used as a scaffold for the development of anticancer agents targeting MDM2.