Analysis of the association between testosterone and cardiovascular disease potential risk factor apolipoprotein B in adult males without cancer: national health and nutrition examination survey 2011-2016.

Background: Over the years, there has been extensive exploration of the association between testosterone and lipid profiles, yet the precise mechanisms underlying their interaction remain incompletely elucidated. Similarly, there is a dearth of research on the correlation between serum apolipoprotein B (apoB) and serum total testosterone (TT), particularly within specific populations. Methods: We conducted a cross-sectional study to assess the relationship between serum TT concentration and serum apoB concentration. Using the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016, we employed weighted generalized linear models, weighted univariate, weighted multivariate analysis, and smooth curve fitting to assist in exploring the relationship between serum TT and apoB. Serum apoB concentration served as the independent variable, and serum TT concentration as the dependent variable. ApoB was divided into four quartiles-Q1 (<0.7g/L, N=691), Q2 (≥0.7g/L to <0.9g/L, N=710), Q3 (≥0.9g/L to <1.1g/L, N=696), and Q4 (≥1.1g/L, N=708)-thereby further solidifying the stable association between the two. Additionally, the application of smooth curve fitting will contribute to a more detailed elucidation of the specific relationship between serum TT concentration and serum apoB concentration under different factors (Drinking, Smoke, Diabetes, Hypertension, and High cholesterol level.). Results: The results indicate a negative correlation between serum TT concentration and apoB concentration (ß=-113.4; 95% CI: -146.6, -80.2; P<0.001). After adjusting for confounding variables, the negative correlation between apoB concentration and TT concentration remains significant (ß=-61.0; 95% CI: -116.7, -5.2; P=0.040). When apoB concentration was converted from a continuous variable to a categorical variable (quartiles: Q1<0.7g/L; Q2:≥0.7g/L to<0.9g/L; Q3:≥0.9g/L to <1.1g/L; Q4: ≥1.1g/L), TT level of participants in the highest quartile (≥1.1g/L) was -47.2 pg/mL (95% CI: -91.2, -3.3; P=0.045) lower than that in the lowest quartile (<0.7g/L). The smooth curve fitting diagram revealed differences in the relationship between TT concentration and apoB among individuals with different cardiovascular disease (CVD) risk factors. Conclusions: This study elucidates a robust inverse correlation between serum TT concentration and apoB concentration, maintaining statistical significance even upon adjustment for confounding factors. These findings present a promising avenue for addressing the prevention and treatment of low testosterone and CVD.

Potential roles of tumor microenvironment in gefitinib-resistant non-small cell lung cancer: A narrative review.

During the course of treating non-small cell lung cancer (NSCLC) with epithelial growth factor receptor (EGFR) mutant, gefitinib resistance (GR) is unavoidable. As the environment for tumor cells to grow and survive, tumor microenvironment (TME) can significantly affect therapeutic response and clinical outcomes, offering new opportunities for addressing GR. Dynamic changes within the TME were identified during the treatment of gefitinib, suggesting the close relationship between TME and GR. Various dynamic processes like angiogenesis, hypoxia-pathway activation, and immune evasion can be blocked so as to synergistically enhance the therapeutic effects of gefitinib or reverse GR. Besides, cellular components like macrophages can be reprogrammed for the same purpose. In this review, we summarized recently proposed therapeutic targets to provide an overview of the potential roles of TME in treating gefitinib-resistant NSCLC, and discussed the difficulty of applying these targets in cancer treatment.

Long-term results of extended Boari flap technique for management of complete ureteral avulsion: A case report.

BACKGROUND: Ureteroscopy is well-established as a primary treatment modality for urolithiasis. Ureteral avulsion, particularly complete or full-length avulsion with a resultant long segment of the ureter left attached to the ureteroscope, is a rare but devastating complication of the procedure. Management of this complication is challenging. Moreover, general consensus regarding the optimal management is undetermined. We report our experience of managing a complete ureteral avulsion case via an extended Boari flap technique with long-term results. CASE SUMMARY: A 41-year-old female patient subjected to complete ureteral avulsion caused by ureteroscopy was referred to our hospital. A modified, extended Boari flap technique was successfully performed to repair the full-length ureteral defect. Maximal mobilization of the bladder and affected kidney followed by psoas hitch and downward nephropexy maximized the probability of a tension-free anastomosis. Meticulous blood supply preservation to the flap also contributed to the success. During the 4-year study period, no complications except for a mild urinary frequency and a slightly lower maximum urinary flow rate were reported. The patient was satisfied with the surgical outcomes. CONCLUSION: The extended Boari flap procedure is a feasible and preferred technique to manage complete ureteral avulsion, particularly in emergencies.

A comprehensive texture feature analysis framework of renal cell carcinoma: pathological, prognostic, and genomic evaluation based on CT images.

OBJECTIVES: We tried to realize accurate pathological classification, assessment of prognosis, and genomic molecular typing of renal cell carcinoma by CT texture feature analysis. To determine whether CT texture features can perform accurate pathological classification and evaluation of prognosis and genomic characteristics in renal cell carcinoma. METHODS: Patients with renal cell carcinoma from five open-source cohorts were analyzed retrospectively in this study. These data were randomly split to train and test machine learning algorithms to segment the lesion, predict the histological subtype, tumor stage, and pathological grade. Dice coefficient and performance metrics such as accuracy and AUC were calculated to evaluate the segmentation and classification model. Quantitative decomposition of the predictive model was conducted to explore the contribution of each feature. Besides, survival analysis and the statistical correlation between CT texture features, pathological, and genomic signatures were investigated. RESULTS: A total of 569 enhanced CT images of 443 patients (mean age 59.4, 278 males) were included in the analysis. In the segmentation task, the mean dice coefficient was 0.96 for the kidney and 0.88 for the cancer region. For classification of histologic subtype, tumor stage, and pathological grade, the model was on a par with radiologists and the AUC was 0.83 [Formula: see text] 0.1, 0.80 [Formula: see text] 0.1, and 0.77 [Formula: see text] 0.1 at 95% confidence intervals, respectively. Moreover, specific quantitative CT features related to clinical prognosis were identified. A strong statistical correlation (R2 = 0.83) between the feature crosses and genomic characteristics was shown. The structural equation modeling confirmed significant associations between CT features, pathological (ß = - 0.75), and molecular subtype (ß = - 0.30). CONCLUSIONS: The framework illustrates high performance in the pathological classification of renal cell carcinoma. Prognosis and genomic characteristics can be inferred by quantitative image analysis. KEY POINTS: • The analytical framework exhibits high-performance pathological classification of renal cell carcinoma and is on a par with human radiologists. • Quantitative decomposition of the predictive model shows that specific texture features contribute to histologic subtype and tumor stage classification. • Structural equation modeling shows the associations of genomic characteristics to CT texture features. Overall survival and molecular characteristics can be inferred by quantitative CT texture analysis in renal cell carcinoma.

Characterization of the Genitourinary Microbiome of 1,165 Middle-Aged and Elderly Healthy Individuals.

Accumulated evidence shows that complex microbial communities resides in the healthy human urinary tract and can change in urological disorders. However, there lacks a comprehensive profiling of the genitourinary microbiota in healthy cohort. Here, we performed 16S rRNA gene sequencing of midstream urine specimens from 1,172 middle-aged and elderly healthy individuals. The core microbiota included 6 dominant genera (mean relative abundance >5%), including Prevotella, Streptococcus, Lactobacillus, Gardnerella, Escherichia-Shigella, and Veillonella, and 131 low-abundance genera (0.01-5%), displaying a distinct microbiome profiles to that of host-matched gut microbiota. The composition and diversity of genitourinary microbiome (GM) were distinct between genders and may fluctuate with ages. Several urotypes were identified by the stratification of microbiome profiles, which were mainly dominated by the six most predominant genera. The prevalence of urotypes was disparate between genders, and the male sample additionally harbored other urotypes dominated by Acinetobacter, Corynebacterium, Staphylococcus, or Sphingomonas. Peptoniphilus, Ezakiella, and Porphyromonas were co-occurred and co-abundant, and they may play crucial roles as keystone genera and be associated with increased microbial diversity. Our results delineated the microbial structure and diversity landscape of the GM in healthy middle-aged and elderly adults and provided insights into the influence of gender and age to it.

Transmucosal Delivery of Self-Assembling Photosensitizer-Nitazoxanide Nanocomplexes with Fluorinated Chitosan for Instillation-Based Photodynamic Therapy of Orthotopic Bladder Tumors.

Theoretically, on account of improved local bioavailability of photosensitizers and attenuated systemic phototoxicity, intravesical instillation-based photodynamic therapy (PDT) for bladder cancer (BCa) would demonstrate significant advantages in comparison with the intravenous route. Actually, the low transmucosal efficiency, hypoxia regulation deficiency, as well as the biosafety risks of intravesical drug agents all have greatly limited the clinical development of instillation-based PDT for BCa. Herein, based on our recent findings on bladder intravesical vectors and photodynamic treatment, we explore and find that the conventional antiparasitic agent nitazoxanide (NTZ) by mixing with chlorine e6 (Ce6) conjugated human serum albumin (HSA), HSA-Ce6, is capable of forming self-assembled HSA-Ce6/NTZ nanoparticles (NPs). Then, the HSA-Ce6/NTZ complexes further fabricate with fluorinated chitosan (FCS), the synthesized transmucosal carrier, to form a biocompatible nanoscale system HSA-Ce6/NTZ/FCS NPs, which exhibit remarkably improved transmucosal delivery and uptake capacities compared with HSA-Ce6/NTZ alone or non-fluorinated HSA-Ce6/NTZ/CS NPs. Meanwhile, due to the metabolic regulation of tumor cells by NTZ, the tumor hypoxia could be efficaciously ameliorated to further favor PDT. This work represents a new photosensitizer nanomedicine formulation for the perfection of PDT performance through the modulation of tumor hypoxia by clinically approved agents. Thus, intravesical instillation of HSA-Ce6/NTZ/FCS NPs with favorable biocompatibility, followed by cystoscope-mediated PDT, could achieve a dramatically improved therapeutic effect to ablate orthotopic bladder tumors.

Fluorinated Chitosan To Enhance Transmucosal Delivery of Sonosensitizer-Conjugated Catalase for Sonodynamic Bladder Cancer Treatment Post-intravesical Instillation.

Sonodynamic therapy (SDT) is a noninvasive ultrasound-triggered therapeutic strategy for site-specific treatment of tumors with great depth penetration. The design of nano-sonosensitizers suitable for SDT treatment of bladder cancer (BCa) post-intravesical instillation has not yet been reported. Herein, a transmucosal oxygen-self-production SDT nanoplatform is developed to achieve highly efficient SDT against BCa. In this system, fluorinated chitosan (FCS) is synthesized as a highly effective nontoxic transmucosal delivery carrier to assemble with meso-tetra(4-carboxyphenyl)porphine-conjugated catalase (CAT-TCPP). The formed CAT-TCPP/FCS nanoparticles after intravesical instillation into the bladder cavity exhibit excellent transmucosal and intratumoral penetration capacities and could efficiently relieve hypoxia in tumor tissues by the catalase-catalyzed O2 generation from tumor endogenous H2O2 to further improve the therapeutic efficacy of SDT to ablate orthotopic bladder tumors under ultrasound. Our work presents a nano-sonosensitizer formulation with FCS to enhance transmucosal delivery and intratumoral diffusion and CAT to improve tumor oxygenation, promising for instillation-based SDT to treat bladder tumors without the concern of systemic toxicity.

miR-216b Post-Transcriptionally Downregulates Oncogene KRAS and Inhibits Cell Proliferation and Invasion in Clear Cell Renal Cell Carcinoma.

BACKGROUND/AIMS: Increasing evidence has shown that miR-216b plays an important role in human cancer progression. However, little is known about the function of miR-216b in renal cell carcinoma. METHODS: The expression levels of miR-216b in renal cell carcinoma tissues and cell lines were examined by qRT-PCR. The biological role of miR-216b in renal cell carcinoma proliferation and/or metastasis was examined in vitro and in vivo. The target of miR-216b was identified by a dual-luciferase reporter assay. The expression level of KRAS protein was measured by western blotting. RESULTS: The expression of miR-216b was downregulated in clear cell renal cell carcinoma (ccRCC) cell lines and specimens compared to the adjacent normal tissues. Furthermore, miR-216b can bind to the 3'untranslated region (UTR) of KRAS and inhibit the expression of KRAS through translational repression. The in vitro study revealed that miR-216b attenuated ccRCC cell proliferation and invasion. Furthermore, in vivo study also showed that miR-216b suppressed tumor growth. MiR-216b exerted its tumor suppressor function through inhibiting the KRAS-related MAPK/ERK and PI3K/AKT pathways. CONCLUSION: Our findings provide, for the first time, significant clues regarding the role of miR-216b as a tumor suppressor by targeting KRAS in ccRCC.

MicroRNA-509-3p inhibits cancer cell proliferation and migration by targeting the mitogen-activated protein kinase kinase kinase 8 oncogene in renal cell carcinoma.

microRNAs (miRNAs; miR) are a class of small non-coding RNA molecules, which are involved in the pathogenesis of human diseases through the negative regulation of gene expression. Previous studies have demonstrated that miR-509-3p is a novel miRNA associated with cell proliferation and migration in 786-O renal cell carcinoma (RCC) cells. However, the mechanism of action of miR-509-3p in RCC remains to be elucidated. The present study aimed to examine the functional role and mechanism of miR-509-3p in the development of RCC. The results demonstrated that the expression levels of miR-509-3p were downregulated in the 786-O and ACHN RCC cell lines compared with the normal tissues of 10 patients with RCC, as determined by reverse transcription-quantitative polymerase chain reaction. The mRNA expression levels of mitogen-activated protein kinase kinase kinase 8 (MAP3K8) were upregulated in the RCC cell lines. Functional investigations demonstrated that the overexpression of miR-509-3p inhibited the migration and proliferation of the RCC cells, as determined by wound scratch and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Luciferase reporter assays revealed that the overexpression of miR-509-3p reduced the transcriptional activity of MAP3K8. Furthermore, the present study demonstrated that the ectopic transfection of miR-509-3p led to a significant reduction in the mRNA and protein expression levels of MAP3K8 in the RCC cells. Finally, knockdown of MAP3K8 inhibited the migration and proliferation of the RCC cells. Therefore, the results of the present study demonstrated that the miR-509-3p RCC suppressor was a significant regulator of the MAP3K8 oncogene, suggesting that it may have a potential therapeutic role in the treatment of RCC.

microRNA-184 functions as tumor suppressor in renal cell carcinoma.

microRNAs (miRNAs) are evolutionarily conserved, endogenous, small, noncoding RNA molecules of approximately 22 nucleotides in length that function as post-transcriptional gene regulators. Their aberrant expression may be involved in human diseases, including cancer. Although miRNA-184 (miR-184) has been reported in other tumors, its function in renal cell carcinoma (RCC) is still unknown. The aim of the present study was to investigate the role of miR-184 in RCC. The impacts of miR-184 on cell migration, proliferation and apoptosis were evaluated using migration scratch, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assay. Our studies revealed that miR-184 mimic significantly inhibits cell migration, suppresses cell proliferation and induces renal cancer cell apoptosis in vitro when compared with the negative control (P<0.05). In this study, it was observed that miR-184 played a significant role as a tumor suppressor in RCC. Therefore, miR-184 may be a promising therapeutic target for renal cancer treatment in the future.

MicroRNA-451a is associated with cell proliferation, migration and apoptosis in renal cell carcinoma.

MicroRNAs (miRNAs) are an important class of small, non­coding RNA molecules that regulate gene expression at the transcriptional or post­transcriptional level. They are involved in apoptosis, proliferation and migration and are known to have an important role in many types of cancer. Aberrant expression of miRNA­451a (miR­451a) has previously been reported in tumors, however its role in renal cell carcinoma (RCC) is currently unknown. The aim of the present study was to investigate the role of miR­451a in RCC. The expression of miR­451a was analyzed in 50 paired RCC and normal tissues by quantitative polymerase chain reaction. Furthermore, the effects of miR­451a on cell migration, proliferation and apoptosis were evaluated, using migration scratch, MTT and flow cytometric assays. The present study demonstrated that miR­451a was upregulated in RCC, as compared with paired normal tissues (P<0.05). Downregulation of miR­451a using a synthesized inhibitor, significantly suppressed cell migration and proliferation, and induced apoptosis of renal cancer cells in vitro, as compared with a negative control (P<0.05). In the present study, it was determined that miR­451a may have an important role as a tumor enhancer in RCC. These results imply that miR­451a may be a promising therapeutic target for the treatment of RCC.