Endocrine-disrupting chemicals (EDCs) are persistent and pervasive compounds that pose serious risks. Numerous studies have explored the effects of EDCs on human health, among which tumors have been the primary focus. However, because of study design flaws, lack of effective exposure levels of EDCs, and inconsistent population data and findings, it is challenging to draw clear conclusions on the effect of these compounds on tumor-related outcomes. Our study is the first to systematically integrate observational studies and randomized controlled trials from over 20 years and summarize over 300 subgroup associations. We found that most EDCs promote tumor development, and that exposure to residential environmental pollutants may be a major source of pesticide exposure. Furthermore, we found that phytoestrogens exhibit antitumor effects. The findings of this study can aid in the development of global EDCs regulatory health policies and alleviate the severe risks associated with EDCs exposure.

BACKGROUND:Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.METHODS:The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.RESULTS:Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.CONCLUSIONS:The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Background: Older adults in low- and middle-income countries (LMICs) often suffer from both sarcopenia and stress urinary incontinence (SUI), two conditions that can significantly impact their health. However, the relationship between these conditions has not been thoroughly explored. Methods: We conducted a cross-sectional study using data from older adults aged 50 years or older from the first wave of the Longitudinal Ageing Study in India (LASI). Participants with complete data on sarcopenia and SUI were included, excluding female participants who were still menstruating. Sarcopenia was defined as decreased grip strength and slow movement. SUI was assessed based on questionnaire responses about whether the participant had ever passed urine when sneezing, coughing, laughing, or lifting heavy objects. We analyzed the data using multiple logistic regression analysis, interaction tests, and stratified analysis. Results: Our results showed that sarcopenia was positively correlated with SUI in male participants after adjusting for adequate confounding factors (odds ratio [OR] = 1.37, 95% confidence interval [CI] [1.20, 1.56], p < 0.001). This correlation remained stable after adjusting for additional confounding factors (OR = 1.27, 95% CI [1.11, 1.45], p < 0.001). In female participants, a stable correlation between sarcopenia and SUI was also observed after adjusting for appropriate confounding factors (OR = 1.11, 95% CI [1.01, 1.23], p = 0.037). According to the results of interaction tests and stratified analysis, the positive correlation between sarcopenia and SUI is notably stronger among men who abstain from alcohol and women who haven't undergone hysterectomy. Conclusions: Sarcopenia and SUI were positively correlated in older Indian adults, regardless of gender. Drinking and a history of hysterectomy may be important influencing factors for both male and female older adults. Further large-scale clinical trials are necessary to confirm this association.

BACKGROUND:As the human body ages, adverse body composition status such as sarcopenia and obesity become obvious phenotypes which can cause numerous health problems. We aimed to comprehensively investigate the association of sex hormones and body mass components in adult men of various age groups. METHODS:We analysed national representative population data from the US National Health and Nutrition Examination Survey. Generalized linear model regression analyses were used to evaluate the association between sex hormones (total testosterone [TT], bio-available testosterone [BT], sex hormone-binding globulin [SHBG], estradiol [E2] and testosterone to estradiol ratio [T/E ratio]) and body mass components (weight, body mass index (BMI), total lean mass, appendicular lean mass, bone mineral content, total fat and trunk fat). The collection and testing time of blood samples were not fixed and there was no strict fasting, but in subsequent analysis we used statistical methods to minimize the impact of random testing. RESULTS:After screening for inclusion and exclusion, 3759 male participants aged 20-85 years old were included in this study. Higher levels of TT, SHBG, BT and T/E ratios were significantly associated with higher total lean mass, appendicular lean mass and bone mineral content, while lower weight, BMI, total fat and trunk fat. For E2 levels in men, we found an opposite trend, with higher E2 levels significantly associated with lower total lean mass and appendicular lean mass, and higher weight, BMI, total fat and trunk fat. Notably, in subgroup analysis, the results showed that there were significant interaction effects of age and smoking history in the association between sex hormones and body mass components. CONCLUSION:Higher TT levels, BT levels, SHBG levels and T/E ratios are associated with lower body weight and improved body composition in young adult men (characterized by higher lean body mass, higher bone density and lower fat mass). The relationship is especially pronounced among relatively young, nonsmoking men.

Background: Urinary incontinence (UI) and erectile dysfunction (ED) often arise as frequent postoperative complications following robotic-assisted radical prostatectomy (RARP) for prostate cancer (PCa). These issues can significantly diminish patients' quality of life (QoL). The assessment of QoL is even more important because treatment decisions may be influenced by the expected QoL. Few studies have integrated the clinical profiles of patients with magnetic resonance imaging (MRI) metrics to assess postoperative UI and ED. Methods: PCa patients treated with RARP between January 2018 and September 2022 were enrolled in this study. Preoperative clinical baseline characteristics and MRI parameters were retrospectively collected. The Expanded Prostate Cancer Index Composite Short Form (EPIC-26) questionnaire was completed to assess urinary continence and sexual function at regular postoperative follow-up. Preoperative baseline clinical characteristics and MRI parameters were subsequently used to screen for predictors of urinary continence and sexual function after RARP, and predictive models were constructed. Results: A total of 627 patients with PCa who met the criteria were ultimately included in this study, with 1059 follow-up questionnaires. The predictive model for postoperative urinary continence was constructed with respect to age, history of transurethral resection of the prostate (TURP) surgery, clinical T stage (cT), Gleason score (GS), Charlson score, membranous urethral length (MUL), pubic symphysis-prostate apex length (PAL), urethral width, right anal sphincter thickness and anal levator muscle thickness (axial plane). Moreover, body mass index (BMI), cT, age, GS, Charlson score, internal obturator muscle thickness, urethral width and anal sphincter thickness were predictors of short-term and long-term postoperative sexual function. We were able to develop highly effective predictive models for postoperative urinary continence and sexual function in RARP patients by incorporating baseline clinical features and MRI parameters. Conclusions: The predictive model enables the assessment of postoperative urinary continence and sexual function in patients after RARP and offers clinical guidance.

Background Increasing body fat or decreasing muscle and bone mass were associated with worse health outcomes in the adult population. The effects of nickel exposure on body composition are not known. The aim of the current study was to investigate the relationship between urinary nickel levels and body compositions. Materials and methods Two thousand seven hundred sixty-two participants were included in the analysis from the National Health and Nutrition Examination Surveys of 2017–2018 after excluding participants who have missing data on urinary nickel and those with missing all body mass component data. We used weighted generalized linear models to explore the relationship between urinary nickel and body mass components under interpolating missing covariable values. Simultaneously, sensitivity analyses and subgroup analysis were conducted to verify stability of analysis result. Curve fitting and saturation effect analysis were used to explore the possible nonlinear relationship between urine nickel and body compositions. Results Among the 2,762 participants, the average urinary nickel level was 1.58 ug/L. The weighted generalized linear models, the sensitivity analyses and subgroup analyses found no significant linear relationship between urinary nickel and body compositions. For body weight, BMI, TLM, ALM, TRF, TOF and BMC, the urine nickel saturation effect values were 0.76, 0.74, 0.5, 0.67, 0.64, 0.48, and 0.45 ug/L, respectively. For each 1 ug/L rise in urinary nickel levels at levels below the turning point, body weight increases (β = 9.06, 95% CI = 2.75, 15.36, p = 0.01), BMI increases (β = 3.20, 95% CI = 1.36, 5.05, p = < 0.001), TLM decreases (β = -47.39, 95% CI = -97.38, 2.59, p = 0.06), ALM decreases (β = -37.25, 95% CI = -63.25, -11.24, p = 0.01), TRF increases (β = 20.68, 95% CI = 1.50, 39.86, p = 0.03), TOF increases (β = 57.92, 95% CI = -0.12, 115.95, p = 0.05), and BMC decreases (β = -6.84, 95% CI = -12.64, -1.04, p = 0.02). Conclusions In summary, our study demonstrated that a dose–response relationship exists between urinary nickel and body compositions, with a low inflection point level of urinary nickel for the saturation effect.

BackgroundChronic kidney disease (CKD) is diagnosed in more than 26 million U.S. people, which increases the risk of many adverse events. α-Klotho was reported to have potential effects on kidney function. The purpose of this study was to investigated whether CKD prevalence is associated with α-Klotho levels in the U.S. people aged 40–79 years.MethodsThirteen thousand five hundred eighty-nine participates in the National Health and Nutrition Examination Survey 2007–2016 aged 40–79 with information of Klotho and kidney function were included. The association between CKD and Klotho was calculated using multivariate linear or logistic regression models with adjustment of several possibly confounding variables. Subgroup analyses stratified by age, BMI, and diabetes mellitus were conducted. The non-linear relationship between Klotho and dependent variables with a non-normality of residues was assessed using smooth curve fitting and the segmented regression (also known as piece-wise regression) models.ResultsAmong 13,589 participants, the median of Klotho levels was 803.10 pg/mL, mean eGFR of all participants was 86.96 (SD = 19.88) mL/min/1.73 m2, and CKD was diagnosed in 20.11% of them (N = 2733). In the fully adjusted model, eGFR was positively associated with Klotho (β = 5.14, 95%CI 4.13-6.15, p < 0.001), while CKD was negatively associated with Klotho (stage ≧ 1, OR = 0.62, 95% CI 0.50–0.76, p < 0.001; stage ≧ 3, OR = 0.31, 95% CI 0.24–0.41, p < 0.001). The non-linear relationship showed that occurrence of CKD stage> 1 and albuminuria were negatively associated with Klotho when Klotho smaller than turning point (for whether CKD stage> 1, turning point K = 6.85, Klotho < K, OR = 0.44, p < 0.001; for albuminuria, turning point K = 6.84, Klotho < K, OR = 0.59, p < 0.001).ConclusionSerum soluble Klotho levels were positively associated with eGFR and negatively associated with the prevalence of CKD, especially in elderly, obese, and diabetic patients.

To the Editor : Testosterone is a fundamental male sex hormone produced by the testicular Leydig cells. Testosterone levels are affected by age, peaking in the 20s and 30s and gradually declining thereafter. [1] Low testosterone level may predispose men, especially older men, to a poor prognosis or death in coronavirus disease 2019 (COVID-19). [2] Therefore, testosterone levels have a signi fi cant impact on the health status of older men. The identi fi ca-tion of modi fi able non-drug factors affecting testosterone levels in older men is important for improving their health. Chronic sleep changes are common in older adults. Testosterone production is dependent on sleep, and plasma testosterone levels vary with a circadian rhythm. However, there is a lack of large-scale population-based studies to explore the effect of sleep duration on testosterone levels in older men. The present study is a cross-sectional analysis based on the West China Health and Aging Trend (WeCHAT) study. WeCHAT is an ongoing prospective multicenter cohort study of community-dwelling Chinese older people and

Introduction After adulthood, as a person grows older, the secretion of sex hormones in the body gradually decreases, and the risk of periodontitis increases. But the relationship between sex hormones and periodontitis is still controversial. Methods We investigated the association between sex hormones and periodontitis among Americans over 30 years old. 4,877 participants containing 3,222 males and 1,655 postmenopausal females who had had periodontal examination and detailed available sex hormone levels, were included in our analysis from the 2009-2014 National Health and Nutrition Examination Surveys cycles. We applied multivariate linear regression models to estimate the connection between sex hormones and periodontitis after converting sex hormones into categorical variables through tertile. Additionally, to ensure the stability of the analysis results, we carried out a trend test, subgroup analysis, and interaction test. Results After fully adjusting the covariates, estradiol levels were not associated with periodontitis in both males and females with a P for trend = 0.064 and 0.064, respectively. For males, we found that sex hormone-binding globulin was positively associated with periodontitis (tertile3 vs tertile1: OR=1.63, 95% CI=1.17-2.28, p = 0.004, P for trend = 0.005). Congruously, free testosterone (tertile3 vs tertile1: OR=0.60, 95% CI=0.43-0.84, p = 0.003), bioavailable testosterone (tertile3 vs tertile1: OR=0.51, 95% CI=0.36-0.71, p < 0.001), and free androgen index (tertile3 vs tertile1: OR=0.53, 95% CI=0.37-0.75, p < 0.001) was found to be negatively associated with periodontitis. Moreover, subgroup analysis of age found a closer relationship between sex hormones and periodontitis in those younger than 50 years. Conclusion Our research suggested that males with lower bioavailable testosterone levels affected by sex hormone-binding globulin were at a higher risk of periodontitis. Meanwhile, estradiol levels were not associated with periodontitis in postmenopausal women.

Dear Editor, Introduced in November 2022, Chat Generative Pre-trained Transformer (ChatGPT) is a large-scale language model designed to answer questions and provide information on a wide range of topics. In the field of medicine, Chat-GPT has demonstrated potential applications: Gilson et al. found that Chat-GPT surpassed a 60% threshold in Step 1 of the National Board of Medical Examiners, equivalent to the passing score of third-year medical students. In another study, Sarraju et al. assessed the appropriateness of Chat-GPT’s responses to fundamental cardiovascular disease prevention questions, identifying 21 out of 25 responses as appropriate. In this study, we aimed to explore the potential application of Chat-GPT4 in surgical oncology by taking the three major urological cancers (prostate cancer, bladder cancer, and renal cell carcinoma) as examples, focusing on determining surgical indications, selecting appropriate surgical techniques, and developing perioperative management plans. We posed 40 questions related to prostate cancer, bladder cancer, and renal cell carcinoma, to which Chat-GPT4 (23March 2023 Version) provided responses (Supplementary Material, Supplemental Digital Content 1, http://links.lww.com/JS9/ A546). Each response was independently evaluated by three urology experts based on guidelines from the European Association of Urology (EAU), American Urological Association (AUA), and National Comprehensive Cancer Network (NCCN), as well as their own clinical practice experience. The responses were scored as 0, 1, 2, or 3, representing complete noncompliance with clinical guidelines and practices or irrelevance; less than 50% compliance with clinical guidelines and practices, with limited guidance value; more than 50% compliance with clinical guidelines and practices, offering some guidance value; and nearly complete compliance with clinical guidelines and practices, providing strong guidance value. Due to the subjectivity of scoring, themedian score among the three experts was considered the final assessment of Chat-GPT4’s responses. Ultimately, among the 40 responses, 1 (2.5%) was scored as 1, 10 (25%) were scored as 2, and 29 (72.5%) were scored as 3 (Table 1). The three experts largely agreed on the scores for each response, with no score difference greater than 1 between any two experts for any response. These results indicate that in the vast majority of cases (97.5%), Chat-GPT4 can provide reasonable responses. In the case where the score was 1, ChatGPT4 recommended conducting a renal biopsy for renal masses incidentally detected via ultrasound to determine the nature of the mass and guide treatment. However, the EAU guidelines state that a renal biopsy is only necessary for elderly or comorbid patients who are considering active surveillance or tumor ablation. As such, although this response was not completely incorrect, it appeared to have limited guidance value. In summary, our study found that Chat-GPT4 can provide reasonable responses to the majority of urological oncologyrelated questions. This demonstrates the tremendous potential of Chat-GPT4 in surgical oncology. However, some limitations of Chat-GPT4 must be acknowledged: First, its data is only updated up to September 2021, and it will not be able to keep pace with changes in standard treatment protocols for cancer, potentially leading to misinformation. Furthermore, experts 2 and 3 believed that many of Chat-GPT4’s responses were too general and lacked specificity, which led them to assign a score of 2 to numerous responses. To obtain accurate and specific answers, appropriate questioning techniques and repeated communication with Chat-GPT4 are required, which may be challenging for nonprofessionals to achieve. From this perspective, Chat-GPT4 can be considered a relatively qualified surgical oncologist, but its assistance to cancer patients may be limited.

Abstract Background Diminished sensitivity towards chemotherapy remains the major impediment to the clinical treatment of bladder cancer. However, the critical elements in control of chemotherapy resistance remain obscure. Methods We adopted improved collagen gels and performed cytotoxicity analysis of doxorubicin (DOX) and mitomycin C (MMC) of bladder cancer cells in a 3D culture system. We then detected the expression of multidrug resistant gene ABCB1, dormancy-associated functional protein chicken ovalbumin upstream-transcription factor 1 (COUPTF1), cell proliferation marker Ki-67, and cellular senescence marker senescence-associated β-galactosidase (SA-β-Gal) in these cells. We further tested the effects of integrin blockade or protein kinase B (AKT) inhibitor on the senescent state of bladder cancer. Also, we examined the tumor growth and survival time of bladder cancer mouse models given the combination treatment of chemotherapeutic agents and integrin α2β1 ligand peptide TFA (TFA). Results Collagen gels played a repressive role in bladder cancer cell apoptosis induced by DOX and MMC. In mechanism, collagen activated the integrin β1/AKT cascade to drive bladder cancer cells into a premature senescence state via the p53/p21 pathway, thus attenuating chemotherapy-induced apoptosis. In addition, TFA had the ability to mediate the switch from senescence to apoptosis of bladder cancer cells in xenograft mice. Meanwhile, TFA combined with chemotherapeutic drugs produced a substantial suppression of tumor growth as well as an extension of survival time in vivo. Conclusions Based on our finding that integrin β1/AKT acted primarily to impart premature senescence to bladder cancer cells cultured in collagen gel, we suggest that integrin β1 might be a feasible target for bladder cancer eradication.

Combined moderate-intensity continuous training aerobic exercise and resistance exercise (MICT/RES) was superior to any other type of exercise in reducing cancer-related fatigue and improving quality of life. MICT/RES was more effective in significantly mitigating urinary and intestinal toxicities.

Background:Hypogonadism has become a major cause endangering men's health and quality of life all over the world. Testosterone Therapy (TT) is a widely accepted treatment for relieving hypogonadal symptoms. However, the effect of different administrations of TT on prostate safety is still unclear. Methods:We did a thorough search of PubMed, Embase and Cochrane Library to identify eligible studies up to January 2022. Randomized controlled trials (RCTs) and Cohort studies evaluating the impacts of using different formulations of TT on prostate parameters were included. Changes of prostate-specific antigen (PSA) level and prostate cancer (Pca) cases were used as the primary outcomes. Quality of individual studies was estimated by RoB2 (Cochrane tool for assessing the risk of bias in randomized trials) and the Newcastle-Ottawa scale (Tool for assessing non-RCTs). Certainty of evidence for each study was evaluated according to the evidence assessment criteria of the Oxford Evidence-based Medicine Center. Random-effect network meta-analysis(NMA)was performed based on the Bayesian model. Results:Thirty-five studies (30 RCTs and 5 Cohort studies) with 7,740 participants were included. TT administration led to fewer Pca patients (RR=0.62, 95%CI [0.39,0.99], I2=0%), while little decreasing in PSA level (MD=-0.05, 95%CI [-0.08, -0.02], I2=0%). The NMA revealed that compared with other formulations, the intramuscular injection was the most likely to rank first in decreasing Pca cases. The TT also resulted in more biopsy cases (RR=2.38, 95%CI [1.01,5.60], I2=0%). As for NMA, intramuscular injection also performed relatively better in fewer prostate biopsy cases compared with transdermal group. Conclusion:TT does not lead to abnormal PSA changes and increased risk of Pca in patients with hypogonadism or low testosterone level. Compared with other preparations of TT, intramuscular injection proved better in minimizing Pca cases and was more likely to result in fewer prostate biopsy cases.