Mapping global research landscape and trend of nano-drug delivery system for urological cancers: a bibliometric analysis.

Aim: We conducted a bibliometric analysis to quantitatively study the development pathway, research hotspots and evolutionary trends of nano-drug delivery systems (NDDS) in treating urological tumors.Materials & methods: We used the Web of Science Core Collection to retrieve the literature related to NDDS in the urological tumors up to November 1, 2023. Bibliometric analysis and visualization were conducted using CiteSpace, VOSviewer and R-Bibliometrix. The major aspects of analysis included contributions from different countries/regions, authors' contributions, keywords identification, citation frequencies and overall research trends.Results: We included 3,220 articles. The analysis of annual publication trends revealed significant growth in this field since 2010, which has continued to the present day. The United States and China have far exceeded other countries/regions in the publication volume of papers in this field. The progression of the shell structure of NDDS in the urinary system has gradually transitioned from non-biological materials to biocompatible materials and ultimately to completely biocompatible materials. Mucoadhesive NDDS for intravesical drug delivery is a hotspot and a potential research material for bladder cancer.Conclusion: The field of NDDS in urological tumors has emerged as a research hotspot. Future research should focus on synergistic effects of NDDS with other treatment modalities.

[Box: see text].

Network pharmacology and molecular docking reveal potential mechanisms of ginseng in the treatment of diabetes mellitus-induced erectile dysfunction and asthenospermia.

Diabetes mellitus (DM) is a chronic metabolic disease that predisposes to chronic damage and dysfunction of various organs, including leading to erectile dysfunction (ED) and asthenospermia. Literature suggests that ginseng plays an important role in the treatment and management of DM. Ginseng may have a therapeutic effect on the complications of DM-induced ED and asthenospermia. The study aimed to explore the mechanisms of ginseng in the treatment of DM-induced ED and asthenospermia following the Traditional Chinese Medicine (TCM) theory of "treating different diseases with the same treatment." This study used network pharmacology and molecular docking to examine the potential targets and pharmacological mechanism of Ginseng for the treatment of DM-induced ED and asthenospermia. The chemical ingredients and targets of ginseng were acquired using the Traditional Chinese Medicine Systems Pharmacology database and analysis platform. The targets of DM, ED, and asthenospermia were extracted with the GeneCards and Online Mendelian Inheritance in Man databases. A protein-protein interaction network analysis was constructed. The Metascape platform was applied for analyzing the gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways. AutoDock Vina was used to perform molecular docking. Network pharmacology revealed that the main active components of the target of action were kaempferol, beta-sitosterol, ginsenoside rh2, stigmasterol, and fumarine. Core targets of the protein-protein interaction network included TNF, IL-1ß, AKT1, PTGS2, BCL2, and JUN. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that they were mainly involved in AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, Lipid and atherosclerosis. The interactions of core active components and targets were analyzed by molecular docking. Ginseng may play a comprehensive therapeutic role in the treatment of DM-induced ED and asthenospermia through "multicomponent, multi-target, and multi-pathway" biological mechanisms such as inflammation and oxidative stress.

A real-world multi-center RNA-seq benchmarking study using the Quartet and MAQC reference materials.

Translating RNA-seq into clinical diagnostics requires ensuring the reliability and cross-laboratory consistency of detecting clinically relevant subtle differential expressions, such as those between different disease subtypes or stages. As part of the Quartet project, we present an RNA-seq benchmarking study across 45 laboratories using the Quartet and MAQC reference samples spiked with ERCC controls. Based on multiple types of 'ground truth', we systematically assess the real-world RNA-seq performance and investigate the influencing factors involved in 26 experimental processes and 140 bioinformatics pipelines. Here we show greater inter-laboratory variations in detecting subtle differential expressions among the Quartet samples. Experimental factors including mRNA enrichment and strandedness, and each bioinformatics step, emerge as primary sources of variations in gene expression. We underscore the profound influence of experimental execution, and provide best practice recommendations for experimental designs, strategies for filtering low-expression genes, and the optimal gene annotation and analysis pipelines. In summary, this study lays the foundation for developing and quality control of RNA-seq for clinical diagnostic purposes.

Sliding mode control strategy based on disturbance observer for permanent magnet in-wheel motor.

A novel sliding mode control(NSMC) strategy combined with a fast terminal sliding mode observer(FTSMO) is suggested in this paper to solve the parameter variation issue of permanent magnet in-wheel motor(PMIWM) installed in the distributed drive electrical vehicle (DDEV). First, a novel sliding mode power converging law is employed to enhance the response speed of the PMIWM controller. Second, an FTSMO is suggested to compensate for the parameter variation of the PMIWM system to strengthen the robustness of the control object. Finally, a fuzzy controller is designed to adjust the control parameters of the NSMC to optimize the control performance. Several simulations and experiments demonstrate that the proposed FTSMO-NSMC scheme can precisely compensate for parameter variation of the control object and improve control accuracy effectively.

ISG15 promotes tumor progression via IL6/JAK2/STAT3 signaling pathway in ccRCC.

Although renal cell carcinoma (RCC) is a prevalent type of cancer, the most common pathological subtype, clear cell renal cell carcinoma (ccRCC), still has poorly understood molecular mechanisms of progression. Moreover, interferon-stimulated gene 15 (ISG15) is associated with various types of cancer; however, its biological role in ccRCC remains unclear.This study aimed to explore the role of ISG15 in ccRCC progression.ISG15 expression was upregulated in ccRCC and associated with poor prognosis. RNA sequence analysis and subsequent experiments indicated that ISG15 modulated IL6/JAK2/STAT3 signaling to promote ccRCC proliferation, migration, and invasion. Additionally, our animal experiments confirmed that sustained ISG15 knockdown reduced tumor growth rate in nude mice and promoted cell apoptosis. ISG15 modulates the IL6/JAK2/STAT3 pathway, making it a potential therapeutic target and prognostic biomarker for ccRCC.

Association between the oxidative balance score and kidney stones in adults.

OBJECTIVES: This study was to investigate the correlation between oxidative balance score (OBS) and the prevalence of kidney stones in the general adult population. MATERIALS AND METHODS: We conducted an analysis using data from the 2007-2018 National Health and Nutrition Examination Survey (NHANES) project, including 17,988 participants. The OBS was computed based on previous research, combining 16 dietary factors and 4 lifestyle factors. Multiple logistic regressions and restricted cubic spline (RCS) regressions were utilized to explore the associations between OBS and kidney stone prevalence. RESULTS: Our analysis included 1,622 adults with kidney stones and 16,366 adults without kidney stones. The average age of participants was 46.86 ± 0.27 years, with 50.72% being male. The median OBS was 22.00 (17.00, 27.00). After adjusting for all covariates, each one-unit increase in OBS was associated with a 3% decrease in kidney stone prevalence (odds ratio [OR] = 0.97 [0.96-0.98], P < 0.001). Moreover, compared to the first quartile, the fourth quartile of OBS (OR = 0.65 [0.50-0.84], P = 0.001) exhibited a negative association with kidney stone prevalence after adjusting for multiple variables. Furthermore, we observed a non-linear negative relationship between OBS and kidney stone prevalence, with inflection points at 18.2 (P for nonlinearity = 0.048). Stratified analysis did not identify any variables significantly affecting the results. CONCLUSION: Our findings indicate that a higher OBS is associated with a decreased prevalence of kidney stones in the general adult population.

Saccharomyces cerevisiae oral immunization in mice using multi-antigen of the African swine fever virus elicits a robust immune response.

African swine fever virus (ASFV) is one of the most complex viruses. ASFV is a serious threat to the global swine industry because no commercial vaccines against this virus are currently available except in Vietnam. Moreover, ASFV is highly stable in the environment and can survive in water, feed, and aerosols for a long time. ASFV is transmitted through the digestive and respiratory tract. Mucosal immunity is the first line of defense against ASFV. Saccharomyces cerevisiae (SC), which has been certified by the U.S. Food and Drug Administration and has a generally recognized as safe status in the food industry, was used for oral immunization in this study. ASFV antigens were effectively expressed in recombinant SC strains with high DNA copy numbers and stable growth though surface display technology and chromosome engineering (δ-integration). The recombinant SC strains containing eight ASFV antigens-KP177R, E183L, E199L, CP204L, E248R, EP402R, B602L, and B646L- induced strong humoral and mucosal immune responses in mice. There was no antigenic competition, and these antigens induced Th1 and Th2 cellular immune responses. Therefore, the oral immunization strategy using recombinant SC strains containing multiple ASFV antigens demonstrate potential for future testing in swine, including challenge studies to evaluate its efficacy as a vaccine against ASFV.

Harmonizing tumor mutational burden analysis: Insights from a multicenter study using in silico reference data sets in clinical whole-exome sequencing (WES).

OBJECTIVES: Tumor mutational burden (TMB) is a significant biomarker for predicting immune checkpoint inhibitor response, but the clinical performance of whole-exome sequencing (WES)-based TMB estimation has received less attention compared to panel-based methods. This study aimed to assess the reliability and comparability of WES-based TMB analysis among laboratories under routine testing conditions. METHODS: A multicenter study was conducted involving 24 laboratories in China using in silico reference data sets. The accuracy and comparability of TMB estimation were evaluated using matched tumor-normal data sets. Factors such as accuracy of variant calls, limit of detection (LOD) of WES test, size of regions of interest (ROIs) used for TMB calculation, and TMB cutoff points were analyzed. RESULTS: The laboratories consistently underestimated the expected TMB scores in matched tumor-normal samples, with only 50% falling within the ±30% TMB interval. Samples with low TMB score (<2.5) received the consensus interpretation. Accuracy of variant calls, LOD of the WES test, ROI, and TMB cutoff points were important factors causing interlaboratory deviations. CONCLUSIONS: This study highlights real-world challenges in WES-based TMB analysis that need to be improved and optimized. This research will aid in the selection of more reasonable analytical procedures to minimize potential methodologic biases in estimating TMB in clinical exome sequencing tests. Harmonizing TMB estimation in clinical testing conditions is crucial for accurately evaluating patients' response to immunotherapy.

Clinical characteristics and identification of novel CNOT1 variants in three unrelated Chinese families with Vissers-Bodmer Syndrome.

Vissers-Bodmer Syndrome, an autosomal dominant disease, is a neurodevelopmental disorder characterized by global developmental delay, intellectual disability, hypotonia and autistic features with a highly variable phenotype. It is caused by variants in the CCR4-NOT transcription complex, subunit 1 gene (CNOT1). However, the pathophysiologic mechanism of the Vissers-Bodmer Syndrome remains unclear. Notably, this syndrome has not been previously reported in the Chinese. In this study, we utilized whole exome sequencing to identify three novel variants in the CNOT1 gene, encompassing one frameshift variant and two missense variants, in three Chinese patients mainly presenting with developmental delay, intellectual disability and/or autism. Interestingly, three patients exhibited novel manifestations including spina bifida occulta, horse-shoe kidney and café-au-lait spot. The frameshift variant, p.Gly172Alafs*5, occurring de novo, leading to a premature stop codon in the protein, was classified into pathogenic. Two missense variants c.3451A > G (p.Asn1151Asp) and c.557C > T (p.Ser186Phe) were predicted to be deleterious by multiple prediction algorithms with high conservation among a variety of species. Additionally, three-dimensional structure modeling and predicting indicated the substitution of the mutated amino acids would decrease the stability of CNOT1 protein. Given that CNOT1 is a relatively novel disease gene, we evaluated the gene-disease validity following ClinGen Standard Operating Procedure. The existing evidence substantiates a "Definitive" level of gene-disease relationship. The genetic findings provide a reliable basis for the genetic counseling of the family reproduction. Moreover, our results expand the genetic and phenotypic spectrum of CNOT1-related Vissers-Bodmer Syndrome.

Serum Iron Levels, Dietary Iron Intake, and Supplement Use in Relation to Metabolic Syndrome in Adolescents: A Cross-Sectional Study.

The objective of this study was to investigate the potential associations between serum iron levels, dietary iron intake, and iron supplementation, and the prevalence of metabolic syndrome (MetS) in adolescents A cross-sectional analysis was conducted, utilizing data from adolescents participating in the 2003-2018 cycle of the National Health and Nutrition Examination Survey (NHANES). Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) pertaining to serum iron, dietary iron, and iron supplementation were derived through multivariate logistic regression models. Additionally, a restricted cubic spline (RCS) regression model was applied to explore the nonlinear relationship between dietary iron and serum iron concerning MetS. The study encompassed 4858 American adolescents aged 12 to 19, among whom 413 (8.5%) manifested MetS. The study cohort exhibited an average age of 15.52 years, comprising 2551 males (52.51%) and 2307 females (47.49%). Relative to individuals in the lowest serum iron quartile, those in the highest quartile for serum iron (OR = 0.33, 95% CI 0.21-0.50), the highest quartile for dietary iron (OR = 0.53, 95% CI 0.32-0.89), and those utilizing iron supplements (OR = 0.61, 95% CI 0.37-0.99) evinced a diminished prevalence of MetS, even post adjustment for potential confounding variables. A non-linear relationship was discerned between serum iron and MetS, exhibiting a statistically significant negative correlation when serum iron concentrations exceeded the inflection point (serum iron = 8.66 µmol/L, P for nonlinear < 0.001). This investigation reveals that higher levels of serum iron, increased dietary iron intake, and the use of iron supplements are linked to a lower prevalence of MetS in US adolescents. These findings suggest that dietary modifications could play a role in promoting the health of adolescents.

Immune regulation and the tumor microenvironment in anti-PD-1/PDL-1 and anti-CTLA-4 therapies for cancer immune evasion: A bibliometric analysis.

This study aims to conduct a bibliometric analysis, employing visualization tools to examine literature pertaining to tumor immune evasion related to anti-CTLA-4 and anti-PD-1/PD-L1 therapy from 1999 to 2022. A special emphasis is placed on the interplay between tumor microenvironment, signaling pathways, immune cells and immune evasion, with data sourced from the Web of Science core collection (WoSCC). Advanced tools, including VOSviewer, Citespace, and Scimago Graphica, were utilized to analyze various parameters, such as co-authorship/co-citation patterns, regional contributions, journal preferences, keyword co-occurrences, and significant citation bursts. Out of 4778 publications reviewed, there was a marked increase in research focusing on immune evasion, with bladder cancer being notably prominent. Geographically, China, the USA, and Japan were the leading contributors. Prestigious institutions like MD Anderson Cancer Center, Harvard Medical School, Fudan University, and Sun Yat Sen University emerged as major players. Renowned journals in this domain included Frontiers in Immunology, Cancers, and Frontiers in Oncology. Ehen LP and Wang W were identified as prolific authors on this topic, while Topalian SL stood out as one of the most cited. Research current situation is notably pivoting toward challenges like immunotherapy resistance and the intricate signaling pathways driving drug resistance. This bibliometric study seeks to provide a comprehensive overview of past and current research trends, emphasizing the potential role of tumor microenvironment, signaling pathways and immune cells in the context of immune checkpoint inhibitors (ICIs) and tumor immune evasion.

Enhancing the quality of panel-based tumor mutation burden assessment: a comprehensive study of real-world and in-silico outcomes.

Targeted panel-based tumor mutation burden (TMB) assays are widely employed to guide immunotherapy for patients with solid tumors. However, the accuracy and consistency of this method can be compromised due to the variability in technical details across different laboratories, particularly in terms of panel size, somatic mutation detection and TMB calculation rules. Currently, systematic evaluations of the impact of these technical factors on existing assays and best practice recommendations remain lacking. We assessed the performance of 50 participating panel-based TMB assays involving 38 unique methods using cell line samples. In silico experiments utilizing TCGA MC3 datasets were performed to further dissect the impact of technical factors. Here we show that the panel sizes beyond 1.04 Mb and 389 genes are necessary for the basic discrete accuracy, as determined by over 40,000 synthetic panels. The somatic mutation detection should maintain a reciprocal gap of recall and precision less than 0.179 for reliable psTMB calculation results. The inclusion of synonymous, nonsense and hotspot mutations could enhance the accuracy of panel-based TMB assay. A 5% variant allele frequency cut-off is suitable for TMB assays using tumor samples with at least 20% tumor purity. In conclusion, this multicenter study elucidates the major technical factors as sources of variability in panel-based TMB assays and proposed comprehensive recommendations for the enhancement of accuracy and consistency. These findings will assist clinical laboratories in optimizing the methodological details through bioinformatic experiments to enhance the reliability of panel-based methods.

Association of dietary carotenoid intake with the prevalence kidney stones among the general adult population.

PURPOSE: This study was to examine whether higher dietary carotenoid intake levels were associated with a lower prevalence of kidney stones. MATERIALS AND METHODS: This study analyzed data from 2007 to 2018 National Health and Nutrition Examination Survey (NHANES) project. Dietary carotenoid intake (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein/zeaxanthin) was assessed using two 24-h dietary recall interviews. Multiple logistic regression and weighted quantile sum (WQS) regression were applied to examine the associations between five dietary carotenoids alone, compounds, and the prevalence of kidney stones. The dose-response relationships were analyzed by restricted cubic spline regression. RESULTS: A total of 30,444 adults (2909 participants with kidney stones) were included in the analysis. The mean age of the participants was 49.95 years and 49.2% of the participants were male. Compared with the first quartile, the fourth quartile of α-carotene (odds ratio [OR] = 0.82 [0.73-0.92]), ß-carotene (OR = 0.79 [0.70-0.89]), ß-cryptoxanthin (OR = 0.88 [0.79-0.99]), and lutein/zeaxanthin (OR = 0.80 [0.71-0.91]) were significantly and inversely associated with the prevalence of kidney stones after adjusting for confounders. The dose-response analysis showed a linear relationship between five dietary carotenoid intake levels and the prevalence of kidney stones. Further WQS analysis revealed that the combination of all five dietary carotenoids was negatively associated with and the prevalence of kidney stones, with the largest effect coming from ß-carotene (weight = 0.538). CONCLUSION: Our findings indicated that higher dietary carotenoid intake levels were associated with decreased prevalence of kidney stones, and increasing the intake of foods rich in ß-carotene may prevent the development of kidney stones.

Identification of P3H1 as a Predictive Prognostic Biomarker for Bladder Urothelial Carcinoma Based on the Cancer Genome Atlas Database.

Purpose: The extracellular matrix in the tumor microenvironment are closely related to the development of tumors. This study's primary aim is to study the association between prolyl 3-hydroxylase 1 (P3H1) which mainly expresses collagen in extracellular matrix and the progression and prognosis of bladder cancer (BC). Methods: The clinical and transcriptome data were acquired from the cancer genome atlas database. BLCAsubtyping is used to evaluate tissue subtypes of BC. The COX proportional hazards can be used to evaluate the survival process's influencing factors. Immunohistochemistry was used to identify differences in the expression of P3H1 in cancer and paired adjacent tissues. GSEA was used to investigate the underlying biological processes. Finally, ssGSEA, TIMER and pRRophetic were used to study the relationship between P3H1 and immune cell infiltration and drug sensitivity. Results: The expression of P3H1 was substantially higher in highly invasive BC samples than in low invasive BC. P3H1 was an independent predictor of overall survival (HR = 1.12, p = 0.03). P3H1 expression was significantly higher in tumor tissues than adjacent normal tissues in clinical tissue samples, and was significantly higher in highly stage cancer than low stage cancer samples. Samples with high P3H1 expression had a higher level of immune cell infiltration and immune function, as well as a significant correlation with macrophage and dendritic cell infiltration and TGF-beta, Th1 cells, and macrophage regulation (cor >0.3, p <0.05). P3H1 high expression samples were substantially more sensitive to docetaxel, cisplatin, vinblastine, camptothecin, paclitaxel, and other medicines than P3H1 low expression samples. Discussion: P3H1 is a possible oncogene and an independent predictor of poor prognosis in BC; it also has enhanced sensitivity to docetaxel, cisplatin, vinblastine, camptothecin, paclitaxel, and other medications.

Risk factors and predictive model for acute kidney Injury Transition to acute kidney disease in patients following partial nephrectomy.

PURPOSE: Acute kidney disease (AKD) is believed to be involved in the transition from acute kidney injury (AKI) to chronic kidney disease in general populations, but little is understood about this possibility among kidney surgical populations. This study aimed to elucidate the incidence of AKD after partial nephrectomy and risk factors that promote the AKI to AKD transition. METHODS: From January 2010 to January 2020, this study retrospectively collected a dataset of consecutive patients with renal masses undergoing partial nephrectomy in 4 urological centers. Cox proportional regression analyses were adopted to identify risk factors that promoted the AKI to AKD transition. To avoid overfitting, the results were then verified by logistic least absolute shrinkage and selection operator (LASSO) regression. A nomogram was then constructed and validated for AKI to AKD transition prediction. RESULTS: AKI and AKD occurred in 228 (21.4%) and 42 (3.9%) patients among a total of 1062 patients, respectively. In patients with AKI, multivariable Cox regression analysis and LASSO regression identified that age (HR 1.078, 1.029-1.112, p < 0.001), baseline eGFR (HR 1.015, 1.001-1.030, p < 0.001), RENAL score (HR1.612, 1.067-2.437, p = 0.023), ischemia time > 30 min (HR 7.284, 2.210-23.999, p = 0.001), and intraoperative blood loss > 300ml (HR 8.641, 2.751-27.171, p < 0.001) were risk factors for AKD transition. These five risk factors were then integrated into a nomogram. The nomogram showed excellent discrimination, calibration, and clinical net benefit ability. CONCLUSION: Around 3.9% patients following partial nephrectomy would transit from AKI to AKD. Intraoperative blood loss and ischemia time need to be diminished to avoid on-going functional decline. Our nomogram can accurately predict the transition from AKI to AKD.

Construction of 3D and 2D contrast-enhanced CT radiomics for prediction of CGB3 expression level and clinical prognosis in bladder cancer.

Objective: The purpose of this study was to construct a 3D and 2D contrast-enhanced computed tomography (CECT) radiomics model to predict CGB3 levels and assess its prognostic abilities in bladder cancer (Bca) patients. Methods: Transcriptome data and CECT images of Bca patients were downloaded from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA) database. Clinical data of 43 cases from TCGA and TCIA were used for radiomics model evaluation. The Volume of interest (VOI) (3D) and region of interest (ROI) (2D) radiomics features were extracted. For the construction of predicting radiomics models, least absolute shrinkage and selection operator regression were used, and the filtered radiomics features were fitted using the logistic regression algorithm (LR). The model's effectiveness was measured using 10-fold cross-validation and the area under the receiver operating characteristic curve (AUC of ROC). Result: CGB3 was a differential expressed prognosis-related gene and involved in the immune response process of plasma cells and T cell gamma delta. The high levels of CGB3 are a risk element for overall survival (OS). The AUCs of VOI and ROI radiomics models in the training set were 0.841 and 0.776, while in the validation set were 0.815 and 0.754, respectively. The Delong test revealed that the AUCs of the two models were not statistically different, and both models had good predictive performance. Conclusion: The CGB3 expression level is an important prognosis factor for Bca patients. Both 3D and 2D CECT radiomics are effective in predicting CGB3 expression levels.

A HER2-targeted Antibody-Drug Conjugate, RC48-ADC, Exerted Promising Antitumor Efficacy and Safety with Intravesical Instillation in Preclinical Models of Bladder Cancer.

More than half of non-muscle-invasive bladder cancer (NMIBC) patients eventually relapse even if treated with surgery and BCG without optional bladder-preserving therapy. This study aims to investigate the antitumor activity and safety of a HER2-targeted antibody-drug conjugate, RC48-ADC, intravesical instillation for NMIBC treatment. In this preclinical study, it is revealed that human epidermal growth factor receptor 2 (HER2) expression scores of 1+, 2+, and 3+ are recorded for 16.7%, 56.2%, and 14.6% of NMIBC cases. The antitumor effect of RC48-ADC is positively correlated with HER2 expression in bladder cancer (BCa) cell lines and organoid models. Furthermore, RC48-ADC is revealed to exert its antitumor effect by inducing G2/M arrest and caspase-dependent apoptosis. In an orthotopic BCa model, tumor growth is significantly inhibited by intravesical instillation of RC48-ADC versus disitamab, monomethyl auristatin E, epirubicin, or phosphate-buffered saline control. The potential toxicity of intravesical RC48-ADC is also assessed by dose escalation in normal nude mice and revealed that administration of RC48-ADC by intravesical instillation is safe within the range of effective therapeutic doses. Taken together, RC48-ADC demonstrates promising antitumor effects and safety with intravesical administration in multiple preclinical models. These findings provide a rational for clinical trials of intravesical RC48-ADC in NMIBC patients.

Associations of the Geriatric Nutritional Risk Index with high risk for prostate cancer: A cross-sectional study.

OBJECTIVES: The geriatric Nutritional Risk Index (GNRI) is an effective tool to assess the nutritional status of the elderly. However, the relationship between the GNRI and the risk for prostate cancer (PCa) remains uncertain in middle-aged and older men. The aim of this study was to investigate the association between the GNRI and the risk for PCa by analyzing the serum total (tPSA) and free prostate-specific antigen (fPSA) levels (including percent fPSA [%fPSA]). METHODS: Data for this study were obtained from 7396 men ≥40 y of age from the 2001-2010 National Health and Nutrition Survey (NHANES). We obtained the tPSA and fPSA and calculated the %fPSA and the GNRI. Participants with %fPSA >25% and tPSA <4 ng/mL were defined as high PCa risk. The relationship between the GNRI and serum PSA levels was investigated using a linear regression model. The odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the GNRI and PCa risk were estimated by a logistic regression model. The non-linear relationship was also characterized by a restricted cubic spline regression model. RESULTS: The median of tPSA, fPSA, and %fPSA was 0.90, 0.26, and 29%, respectively. The mean of the GNRI was 29. The proportion of participants in the low PCa- and high PCa-risk groups was 93% and 7%, respectively. There was a negative and linear correlation between the GNRI and serum tPSA and fPSA levels in all models. However, no association between the GNRI and the %fPSA was observed. In the adjusted model, lower GNRI was associated with higher PCa risk (OR, 0.570; 95% CI, 0.415-0.784; Ptrend = 0.001). The restricted cubic spline regression model showed a non-linear and negative association between the GNRI and PCa risk (Pnon-linearity = 0.020), with inflection points of 109.148. CONCLUSION: The results of this study suggest that nutritional status, as represented by the GNRI, is associated with the risk for PCa.

Comparison of analytical sensitivity of DNA-based and RNA-based nucleic acid amplification tests for reproductive tract infection pathogens: implications for clinical applications.

Currently, DNA-based nucleic acid amplification tests (NAATs) and RNA-based NAATs are employed to detect reproductive tract infection (RTI) pathogens including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Ureaplasma urealyticum (UU). Although evaluations of DNA-based NAATs have already existed, the comparison of the two methods is scarce. Thus, we compared the limits of detection (LODs) of DNA-based and RNA-based NAATs on the same experimental conditions. Inactivated culture supernatants of CT, NG, and UU with determined pathogen DNA and RNA load were used to evaluate LODs of seven DNA kits and one RNA kit. The LODs of the seven DNA kits for CT, NG, and UU ranged between 38-1,480, 94-20,011, and 132-2,011 copies/mL, respectively. As for RNA kits, they could detect samples at RNA concentrations of 3,116, 2,509, and 2,896 copies/mL, respectively. The RNA concentrations of CT, NG, and UU were 40, 885, and 42 times that of corresponding pathogen DNA concentrations in the employed supernatants, so RNA kits could detect pathogen DNA concentrations as low as 78 copies/mL, 3 copies/mL, and 69 copies/mL, respectively, but the level of pathogen load that the RNA tests could detect was primarily dependent on the infectious phase and transcriptional level of RNA. Thus, a schematic of bacterial dynamics during the period of reproductive tract infections was provided, which suggests that in terms of the analytical sensitivity of pathogen detection, RNA tests are more suitable for detecting active infection and recovery phase, while DNA tests are more suitable for detection in the early stage of infection. IMPORTANCE Reproductive tract infections have considerable effects on the health of humans. CT, NG , and UU are common pathogens. Although evaluation of DNA-based tests has already existed, the comparison between DNA-based and RNA-based tests is rare. Therefore, this study compared the limits of detection of the two tests on the same experimental conditions. Results suggested that most DNA-based NAATs could detect CT, NG, and UU at DNA concentrations lower than 1,000 copies/mL, while RNA-based NAATs could detect bacteria at RNA concentrations around 3,000 copies/mL. Considering the copy number of RNA per bacterium is dynamic through the growth cycle, further comparison is combined with a schematic of bacterial dynamics. Results suggested that in terms of the analytical sensitivity of pathogen detection, RNA tests are more suitable for detecting active infection and recovery phase, while DNA tests are more suitable for detection in the early stage of infection.