Efficacy and safety of antibody-drug conjugates in the treatment of urothelial cell carcinoma: a systematic review and meta-analysis of prospective clinical trials.

Introduction: Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug conjugates (ADCs) are a novel class of targeted therapeutics that have demonstrated encouraging results for UC. Although there is a limited number of high-quality randomized control trials (RCTs) examining the use of ADCs in patients with UC, some prospective non-randomized studies of interventions (NRSIs) provide valuable insights and pertinent information. We aim to assess the efficacy and safety of ADCs in patients with UC, particularly those with locally advanced and metastatic diseases. Methods: A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science databases to identify pertinent studies. Outcomes, such as the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs), were extracted for further analyses. Results: Twelve studies involving 1,311 patients were included in this meta-analysis. In terms of tumor responses, the pooled ORR and DCR were 40% and 74%, respectively. Regarding survival analysis, the pooled median PFS and OS were 5.66 months and 12.63 months, respectively. The pooled 6-month PFS and OS were 47% and 80%, while the pooled 1-year PFS and OS were 22% and 55%, respectively. The most common TRAEs of the ADCs were alopecia (all grades: 45%, grades ≥ III: 0%), decreased appetite (all grades: 34%, grades ≥ III: 3%), dysgeusia (all grades: 40%, grades ≥ III: 0%), fatigue (all grades: 39%, grades ≥ III: 5%), nausea (all grades: 45%, grades ≥ III: 2%), peripheral sensory neuropathy (all grades: 37%, grades ≥ III: 2%), and pruritus (all grades: 32%, grades ≥ III: 1%). Conclusion: The meta-analysis in this study demonstrates that ADCs have promising efficacies and safety for patients with advanced or metastatic UC. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023460232.

Association between magnesium depletion score and the prevalence of kidney stones in the low primary income ratio: a cross-sectional study of NHANES 2007-2018.

INTRODUCTION: To explore the association between magnesium depletion score (MgDS) and the prevalence of kidney stones in the low primary income ratio (PIR). METHOD: A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey 2007-2018. Within the low PIR, people aged ≥20 years with complete information on MgDS and kidney stones questionnaires were enrolled. Multivariable logistic regression and stratified logistic regression analyses were performed to examine the association between MgDS and the prevalence of kidney stones and recurrence of kidney stones by confounding factors adjusted. Stratified and interaction analysis was conducted to find whether some factors modified the association. In addition, sensitive analyses were also conducted to observe the stability. The work has been reported in line with the STROCSS criteria, Supplemental Digital Content 1, http://links.lww.com/JS9/C781. RESULT: A total of 7,600 adults were involved in the study, and the individuals were classified into four groups: 0 points for MgDS (n=3,814), 1 point for MgDS (n=2,229), 2 points for MgDS (n=1,020), and ≥3 points for MgDS (n=537). The multivariable logistic regression suggested that a positive association between MgDS and the prevalence of kidney stones (OR=1.123, 95%CI 1.019 to 1.238) in the fully-adjusted model. Compared with the lowest group, people with ≥3 points of MgDS had a had a significant relationship with kidney stones (OR=1.417, 95%CI 1.013 to 1.983). No significant association was observed between the recurrence of kidney stones and MgDS. The result of the sensitive analysis showed the robustness of the main analysis. CONCLUSION: The prevalence of kidney stones is inversely associated with MgDS, which suggests that maintaining a higher MgDS is accompanied by higher prevalence rates of kidney stones in the low PIR.

Association Between Physical Activity and the Prevalence of Kidney Stones in American Adults: Results From a Multiyear National Survey.

OBJECTIVE: To investigate the association between physical activity (PA) and the prevalence of kidney stones. METHODS: A cross-section study was conducted using data from National Health and Nutrition Examination Survey 2007-2018. PA was evaluated based on the Global Physical Activity Questionnaire. Multivariable logistic regression was performed to elucidate the association between PA (patterns, intensity, duration, and frequency of moderate and vigorous PA) and the prevalence of kidney stones after adjusting for potential confounders. Stratified and interaction analyses were conducted to detect potential effect modifiers. In addition, PA was assessed using metabolic equivalent and physical volume, and followed the regression above. Water intake was obtained from the day 2 dietary recall and was included in the sensitivity analysis. RESULTS: A total of 34,390 participants were included in the analysis. The multivariable logistic regression revealed that individuals who engaged in moderate PA for 30-60 minutes per day had a significant inverse association with the prevalence of kidney stones in the fully adjusted model (odds ratio=0.804, 95% confidence interval 0.700 to 0.923), while no more significant finding was observed for other PA parameters. Interaction and stratified analyses indicated no covariate modifying the association. The results above were robust in the sensitivity analysis. CONCLUSION: The duration of moderate PA (30-60 min/d) is inversely associated with the prevalence of kidney stones, while no more significant association was observed between other PA parameters (including patterns, intensity, duration, and frequency of vigorous PA, frequency of moderate PA) and kidney stones.

A review for the impacts of circadian disturbance on urological cancers.

Circadian rhythm is an internal timing system and harmonizes a variety of cellular, behavioral, and physiological processes to daily environment. Circadian disturbance caused by altered life style or disrupted sleep patterns inevitably contributes to various disorders. As the rapidly increased cancer occurrences and subsequent tremendous financial burdens, more researches focus on reducing the morbidity rather than treating it. Recently, many epidemiologic studies demonstrated that circadian disturbance was tightly related to the occurrence and development of cancers. For urinary system, numerous clinical researches observed the incidence and progress of prostate cancer were influenced by nightshift work, sleep duration, chronotypes, light exposure, and meal timing, this was also proved by many genetic and fundamental findings. Although the epidemiological studies regarding the relationship between circadian disturbance and kidney/bladder cancers were relative limited, some basic researches still claimed circadian disruption was closely correlated to these two cancers. The role of circadian chemotherapy on cancers of prostate, kidney, and bladder were also explored, however, it has not been regularly recommended considering the limited evidence and poor standard protocols. Finally, the researches for the impacts of circadian disturbance on cancers of adrenal gland, penis, testis were not found at present. In general, a better understanding the relationship between circadian disturbance and urological cancers might help to provide more scientific work schedules and rational lifestyles which finally saving health resource by reducing urological tumorigenesis, however, the underlying mechanisms are complex which need further exploration.

Sexual dysfunction in patients with diabetes: association between remnant cholesterol and erectile dysfunction.

BACKGROUND: Erectile dysfunction (ED) is closely associated with dyslipidemia; however, it is yet unknown how ED and remnant cholesterol (RC) are related. As such, this research sought to explore the correlation between RC and ED among individuals with diagnosed with diabetes. METHODS: This cross-sectional study used information from 215 males from National Health and Nutrition Examination Survey (NHANES) from 2001 to 2004. RC was calculated as follows: the values of high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) were subtracted from the total cholesterol (TC) value, while ED diagnoses were based on self-reports. Weighted logistic regression analyses using both univariate and multivariate approaches were conducted to assess the correlation between RC and ED. RESULTS: After comprehensive adjustment, multivariable logistic regression models revealed a strong correlation between RC and ED in subjects with diabetes (with an odds ratio (OR) of 7.49 and a 95% confidence interval (CI) of 1.98-28.37; P = 0.004). On categorizing RC into 3 grades (T1-T3), the OR corresponding to higher RC grade increased. Despite the results not reaching statistical significance upon categorization, a consistent and statistically significant trend (P for trend < 0.05) was observed. CONCLUSION: This study indicated a correlation between increased RC levels and a higher prevalence of ED in diabetic males. RC may serve as a promising predictor of ED in individuals with diabetes. However, additional studies are required to confirm these findings.

Sleep and circadian rhythm disturbance in kidney stone disease: a narrative review.

The circadian rhythm generated by circadian clock genes functions as an internal timing system. Since the circadian rhythm controls abundant physiological processes, the circadian rhythm evolved in organisms is salient for adaptation to environmental change. A disturbed circadian rhythm is a trigger for numerous pathological events. Recently, accumulated data have indicated that kidney stone disease (KSD) is related to circadian rhythm disturbance. However, the mechanism between them has not been fully elucidated. In this narrative review, we summarized existing evidence to illustrate the possible association between circadian rhythm disturbance and KSD based on the epidemiological studies and risk factors that are linked to circadian rhythm disturbance and discuss some chronotherapies for KSD. In summary, KSD is associated with systemic disorders. Metabolic syndrome, inflammatory bowel disease, and microbiome dysbiosis are the major risk factors supported by sufficient data to cause KSD in patients with circadian rhythm disturbance, while others including hypertension, vitamin D deficiency, parathyroid gland dysfunction, and renal tubular damage/dysfunction need further investigation. Then, some chronotherapies for KSD were confirmed to be effective, but the molecular mechanism is still unclear.

A positive association between the prevalence of circadian syndrome and overactive bladder in United States adults.

Objective: To explore the association between the prevalence of circadian syndrome (CircS) and overactive bladder (OAB). Materials and methods: Cross-section analysis was based on the National Health and Nutrition Examination Survey 2005-2018. Data regarding OAB was collected from questionnaires. The association between the prevalence of CircS and OAB was elucidated using three multivariable logistic regression models. Stratified and interaction analyses were performed to find whether some factors can modify the association. Results: Totally 8,033 males and 8,065 females were included. People with CircS had a significantly higher prevalence of OAB compared to the non-CircS group in the fully-adjusted model (OR = 1.238, 95%CI 1.080-1.419). A significant positive correlation between the number of CircS components and the prevalence of OAB was observed when the components were ≥ 6 (OR = 1.975, 95%CI 1.463-2.665). No significant interaction was seen in the three models. Conclusion: There is a positive association between the prevalence of CircS and OAB. When the number of components is ≥6, the prevalence of OAB shows a strongly positive correlation with the number of CircS components.

Association between the prevalence rates of circadian syndrome and testosterone deficiency in US males: data from NHANES (2011-2016).

Objective: The objective of this study is to explore the association between the prevalence rates of circadian syndrome (CircS) and testosterone deficiency (TD). Materials and methods: Cross-sectional analysis was conducted on the basis of the National Health and Nutrition Examination Survey 2011-2016. The target population was males aged ≥20 years old. A total of three multivariable logistic regression models were built to elucidate the association between the prevalence rates of CircS and TD. Interactive and stratified analyses were employed to explore whether some variables can modify the above association. Sensitivity analyses were also conducted to verify the stability of the results with extreme values removed. Results: A total of 3,436 eligible participants were involved. Multivariable logistic regression in the fully adjusted model suggested the CircS group had a significantly higher prevalence rate of TD compared with the non-CircS group (OR = 2.284, 95%CI 1.569 to 3.323). No significant correlation between the number of CircS components and TD was observed in any of the three models. The interactive and stratified analyses showed the association was more obvious in the population with moderate or vigorous activities. The results were robust after extreme data were excluded. Conclusion: There is a positive association between the prevalence rates of CircS and TD in US men. The association becomes more obvious owing to moderate or vigorous activities.

Association between circadian syndrome and the prevalence of kidney stones in overweight adults: a cross-sectional analysis of NHANES 2007-2018.

OBJECTIVE: To explore the association between circadian syndrome (CircS) and the prevalence of kidney stones in overweight people. MATERIALS AND METHODS: A cross-sectional analysis was conducted based on the NHANES 2007-2018. Overweight people aged ≥ 20 years were the target population. Three multivariable logistic regression models were built to examine the association between CircS and kidney stones. Subgroup analysis based on age, gender, and race were also employed. Interaction and stratification analysis was also conducted to identify whether some factors modify the association. RESULT: A total of 4,603 overweight participants were included in the study. The multivariable logistic regression suggested that CircS was positively associated with the prevalence of kidney stones (OR = 1.422, 95% CI 1.057 to 1.912). The subgroup analysis showed that the association was more obvious in females (OR = 1.604, 95% CI 1.023 to 2.516) or in the population aged 35 to 49 years old (OR = 2.739, 95% CI 1.428 to 5.254). Additionally, the same trend was present when people were Mexican American (OR = 3.834, 95% CI 1.790 to 8.215) or other races (OR = 4.925, 95% CI 1.776 to 13.656). The interaction and stratification analysis showed that the results above were robust. CONCLUSION: CircS was positively associated with the prevalence of kidney stones in overweight people, especially people as females, aged 35 to 49, and Mexican Americans.

Clock gene NR1D1 might be a novel target for the treatment of bladder cancer.

PURPOSE: To explore the role of circadian clock gene NR1D1 (REV-erbα) in bladder cancer (BC). METHODS: Firstly, the association of NR1D1 level with clinical characteristics and prognosis was investigated among patients diagnosed with BC. Secondly, CCK-8, transwell, and colony formation experiments were performed among BC cells treated with Rev-erbα agonist (SR9009), as well as lentivirus and siRNA, for which NR1D1 were overexpressed (OE) and knocked down (KD), respectively. Thirdly, cell cycle and apoptosis were tested by flowcytometry. PI3K/AKT/mTOR pathway proteins were determined in OE-NR1D1 cells. Finally, OE-NR1D1 and OE-Control BC cells were subcutaneously implanted in BALB/c nude mice. The tumor size and protein levels were compared between groups. A P < 0.05 was considered as statistically significant. RESULTS: Patients with NR1D1 positive status had a longer disease-free survival than those with negative expression. The cell viability, migration, and colony formation of BC cells after treated with SR9009 were significantly suppressed. OE-NR1D1 cells had obviously inhibited cell viability, migration, and colony formation, while those were found strengthened in KD-NR1D1 cells. Besides, KD-NR1D1 cells were observed with a lower proportion of dead cells and G0/G1 cells, but a higher ratio of G2/M. The changes of p-AKT, p-S6, p-4EBP1, and FASN involved in PI3K/AKT/mTOR pathway were detected in OE- and KD-NR1D1 BC cells. Finally, in vivo data demonstrated that overexpression of NR1D1 suppressed the tumorigenicity of BC cells. CONCLUSION: NR1D1 played a role of tumor suppressor and it might become a novel target for the treatment of BC.

Nanoarchitectonics-Assisted Simultaneous Fluorescence Detection of Urinary Dual miRNAs for Noninvasive Diagnosis of Prostate Cancer.

Herein, we report a fluorescence strategy for the homogeneous and simultaneous analysis of urine miRNA-375 and miRNA-148a. The target miRNAs in urine bonded the devised dumbbell-shaped "C-Ag+-C" and "T-Hg2+-T" hairpin structures that could trigger cascade enzyme-free amplification. Then, the fluorescent CdTe quantum dots (QDs) and carbon dots (CDs) could selectively recognize Ag+ and Hg2+, to quantify the dual miRNAs concurrently. Under optimized conditions, the linear range was from 0.1 to 1000 fM and the limits of detection (LOD) for dual miRNAs reached 30 and 25 aM, respectively. The practicality was further evaluated with 45 clinical urine samples including prostate cancer (PC) and other patients, and the results were consistent with the clinical polymerase chain reaction (PCR) kit and ultrasonic and pathological findings. The receiver operating characteristic (ROC) curve analysis showed that the estimates of the area under the curve (AUC) were 0.739 for the serum prostate-specific antigen (PSA) and 0.941 for miRNA-375 and 0.946 for miRNA-148a. The sensitivity and specificity reached 75 and 100% for miRNA-375 and 71 and 94% for miRNA-148a, respectively, which was better than serum PSA. This strategy constructed a reliable system for dual miRNA detection in urine samples and proposed new insights into the rapid and noninvasive diagnosis of PC.

Obesity, metabolic dysfunction, and risk of kidney stone disease: a national cross-sectional study.

BACKGROUND: This study aimed to investigate the association between different metabolic syndrome-body mass index (MetS-BMI) phenotypes and the risk of kidney stones. MATERIALS AND METHODS: Participants aged 20-80 years from six consecutive cycles of the NHANES 2007-2018 were included in this study. According to their MetS status and BMI, the included participants were allocated into six mutually exclusive groups: metabolically healthy normal weight (MHN)/overweight (MHOW)/obesity (MHO) and metabolically unhealthy normal weight (MUN)/overweight (MUOW)/obesity (MUO). To explore the association between MetS-BMI phenotypes and the risk of kidney stones, binary logistic regression was used to determine the odds ratios (ORs). RESULTS: A total of 13,589 participants were included. It was revealed that all the phenotypes with obesity displayed higher risks of kidney stones (OR = 1.38, p < 0.01 for MHO & OR = 1.80, p < 0.001 for MUO, in the fully adjusted model). The risk increased significantly when metabolic dysfunction coexisted with overweight and obesity (OR = 1.39, p < 0.05 for MUOW & OR = 1.80, p < 0.001 for MUO, in the fully adjusted model). Of note, the ORs for the MUO and MUOW groups were higher than those for the MHO and MHOW groups, respectively. CONCLUSIONS: Obesity and unhealthy metabolic status can jointly increase the risk of kidney stones. Assessing the metabolic status of all individuals may be beneficial for preventing kidney stones.

Prognostic value of COL10A1 and its correlation with tumor-infiltrating immune cells in urothelial bladder cancer: A comprehensive study based on bioinformatics and clinical analysis validation.

Introduction: Bladder cancer (BLCA) is one of the most lethal diseases. COL10A1 is secreted small-chain collagen in the extracellular matrix associated with various tumors, including gastric, colon, breast, and lung cancer. However, the role of COL10A1 in BLCA remains unclear. This is the first research focusing on the prognostic value of COL10A1 in BLCA. In this research, we aimed to uncover the association between COL10A1 and the prognosis, as well as other clinicopathological parameters in BLCA. Methods: We obtained gene expression profiles of BLCA and normal tissues from the TCGA, GEO, and ArrayExpress databases. Immunohistochemistry staining was performed to investigate the protein expression and prognostic value of COL10A1 in BLCA patients. GO and KEGG enrichment along with GSEA analyses were performed to reveal the biological functions and potential regulatory mechanisms of COL10A1 based on the gene co-expression network. We used the "maftools" R package to display the mutation profiles between the high and low COL10A1 groups. GIPIA2, TIMER, and CIBERSORT algorithms were utilized to explore the effect of COL10A1 on the tumor immune microenvironment. Results: We found that COL10A1 was upregulated in the BLCA samples, and increased COL10A1 expression was related to poor overall survival. Functional annotation of 200 co-expressed genes positively correlated with COL10A1 expression, including GO, KEGG, and GSEA enrichment analyses, indicated that COL10A1 was basically involved in the extracellular matrix, protein modification, molecular binding, ECM-receptor interaction, protein digestion and absorption, focal adhesion, and PI3K-Akt signaling pathway. The most commonly mutated genes of BLCA were different between high and low COL10A1 groups. Tumor immune infiltrating analyses showed that COL10A1 might have an essential role in recruiting infiltrating immune cells and regulating immunity in BLCA, thus affecting prognosis. Finally, external datasets and biospecimens were used, and the results further validated the aberrant expression of COL10A1 in BLCA samples. Conclusions: In conclusion, our study demonstrates that COL10A1 is an underlying prognostic and predictive biomarker in BLCA.

Rapid binary visual detection of oxalate in urine samples of urolithiasis patients via competitive recognition and distance reading test strips.

Urolithiasis is a common disease with wide ranging effects, with oxalate stones being the most prevalent type. Existing clinical diagnostic methods rely on complex instruments and professionals, are difficult to distinguish between stone types, and have insufficient sensitivity. Moreover, high-sensitivity point-of-care testing (POCT) methods remain scarce. We constructed a rapid homogeneous dual fluorescence and binary visualization analysis system to diagnose oxalate urolithiasis because oxalate can efficiently reduce Cu2+ to Cu+, which can be selectively competitively recognized by both calcein and cadmium telluride quantum dots (CdTe QDs). Under optimized conditions, the system exhibited high sensitivity to oxalate ranging from 10 pM to 10 nM within 3 min. Following that, visualized test strips of calcein and QDs were generated by inkjet printing; oxalate concentrations as low as 10 nM can be easily identified by reading the quenching distance on the strip. We then analyzed 66 clinical urine samples: 11 healthy, 10 oxalate-negative, and 45 oxalate-positive samples. The fluorescence and visual mode results were highly consistent with clinical computed tomography (CT) images and clinical diagnostics. Therefore, our analysis strategy has the potential to use POCT for the assessment of oxalate urolithiasis.

A cross-sectional analysis of association between visceral adiposity index and serum anti-aging protein Klotho in adults.

Background: The visceral adiposity index (VAI) is regarded as a reliable indicator to assess body fat distribution and dysfunction. Klotho protein is a hormone with anti-aging biological functions. However, the relationship between them has not been researched. Objects: This study aimed to evaluate the association between VAI and serum anti-aging protein klotho in American adults. Methods: A cross-sectional study of participants was conducted based on the National Health and Nutrition Examination Surveys (NHANES) 2007-2016. Visceral adiposity was determined using the VAI score, while the klotho protein concentration was measured by ELISA kit. After adjusting some possible confounding variables, multivariate regression model was conducted to estimate the relationship between VAI and klotho protein. Furthermore, the smooth curve fitting and the segmented regression model were applied to examine the threshold effect and to calculate the inflection point. Result: In total, 6 252 adults were eligible, with a mean VAI of 2.04 ± 0.03 and a mean klotho protein concentration of 848.79 ± 6.98 pg/ml. Multivariate regression analysis indicated that serum klotho protein concentration was lower in participants with high VAI score. When VAI was divided into quartiles, participants in the fourth quartiles of higher VAI had lower klotho protein levels (Q4: -32.25 pg/ml) than participants in the lowest quartile (Q1) after full adjustment (P < 0.05). Segmented regression suggested that the turning point value of VAI was 3.21. A 1-unit increase in VAI was significantly associated with lower klotho protein levels by -18.61 pg/ml (95% CI: -28.87, -8.35; P < 0.05) when VAI ranged from 0.29 to 3.21(accounting for 83.7% of the participants), however, the association was not significant when VAI ranged from 3.21 to 11.81 (P = 0.77). Conclusion: There was a nonlinear correlation between VAI score and the serum anti-aging protein klotho concentrations, showing a saturation effect. When VAI was less than 3.21, they were negatively correlated, and when VAI was greater than 3.21, they had no obvious correlation.