Metabolic health is closely related to testosterone levels, and the cardiometabolic index (CMI) is a novel metabolic evaluation metric that encompasses obesity and lipid metabolism. However, there is currently a lack of research on the relationship between CMI and testosterone, which is the objective of this study. This study utilized data from the National Health and Nutrition Examination Survey (NHANES) cycles from 2011 to 2016. Only adult males who completed physical measurements, lipid metabolism assessments, and testosterone measurements were included in the final analysis. The exposure variable CMI was analyzed both as a continuous variable and a categorical variable divided into quartiles. Testosterone was measured using the isotope dilution liquid chromatography-tandem mass spectrometry technique. Linear and logistic regression analyses were used to explore the relationship between CMI and total testosterone (TT) levels, as well as the risk of testosterone deficiency (TD). Smooth curve fittings were employed to visualize their linear relationships. Subgroup analyses were conducted to evaluate the stability of our results across different participant characteristics. Finally, ROC analysis was used to assess the performance of CMI in predicting TD. A total of 2,747 participants were included in the analysis, including 552 with TD (20.10

BACKGROUND:Acute kidney injury (AKI) is a prevalent and life-threatening condition characterized by abrupt renal function decline and subsequent inflammatory cascades. PANoptosis has emerged as a significant contributor to the pathophysiology of AKI. This research aimed to explore the diagnostic and therapeutic implications of PANoptosis-related genes in AKI. METHODS:Kidney biopsy transcriptomic expression data were obtained from the GEO database. Differentially expressed genes (DEGs) associated with PANoptosis were identified between AKI and controls. WGCNA identified hub PANoptosis-related genes. PANoptosis scores and immune cell infiltration were calculated by ssGSEA. Machine learning algorithms was used to select feature genes. ROC analysis evaluated their diagnostic performance. Drug-gene interactions were explored. RESULTS:We identified 3460 DEGs between AKI and controls (61 upregulated and 11 downregulated) related to PANoptosis, mainly enriched in cytokine signaling and apoptosis. Eight hub PANoptosis genes were identified. PANoptosis scores were significantly higher in AKI patients (p < 0.001). CASP8, CASP4, SFN, FAS, and CASP1 were selected as feature genes, with CASP8 having the highest AUC at 0.850 in the training set. A nomogram combining these genes demonstrated strong predictive power. Furthermore, these genes were related to immune cell infiltration positively and had potential drug associations. Validation in a renal ischemia-reperfusion injury rat model confirmed the upregulation of CASP8 (p < 0.01), CASP4 (p < 0.001), SFN (p < 0.0001), FAS (p < 0.01), and CASP1 (p < 0.01). CONCLUSIONS:Our study identifies PANoptosis-related genes as potential diagnostic markers and therapeutic targets in AKI, highlighting their role in immune dysregulation in AKI.

Abstract Background: Despite the very high sensitivity of the Systemic Inflammatory Response Syndrome (SIRS) score for identifying sepsis, there remains a subset of septic patients who exhibit negative SIRS scores, and unfortunately, many of these patients experience poor outcomes. This study aims to investigate the factors associated with SIRS negativity during the early stage of sepsis in deceased patients, and to explore the nonlinear relationships between SIRS negativity and these factors. Objective: To analyse the factors related to systemic inflammatory response syndrome (SIRS) negativity during the early stage of sepsis in nonsurviving septic patients and to explore the nonlinear associations between SIRS negativity and related factors. Methods: Adult septic patients were retrospectively screened in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database from 2008 to 2019. Patients who did not survive after 28 days were assigned to the SIRS-negative or SIRS-positive group according to whether the SIRS score was less than two points within 24 hours of intensive care unit (ICU) admission. The baseline data of patients in the SIRS-negative and SIRS-positive groups were collected and compared. The factors associated with SIRS negativity in septic patients were analysed by logistic regression. The dose‒response relationships of SIRS negativity with SOFA score and age were determined with a restricted cubic spline model. Results: A total of 53,150 patients were screened in the MIMIC-IV database, and 2706 sepsis nonsurvivors were ultimately included, 101 of whom were negative for SIRS. There were significant differences in SOFA scores between groups (8.18±3.58 vs. 9.75±4.28, P<0.001). In addition, differences in several other parameters, such as age (76 [61 to 86] vs. 72 [60 to 82], P=0.053), body mass index (26 [22 to 31] vs. 27 [24 to 32], P=0.056) and Charlson comorbidity index (8 [6 to 9] vs. 7 [5 to 9], P=0.052], approached statistical significance. Logistic regression analysis indicated that both SOFA score (OR=0.93 [95% CI=0.87-1.00], P=0.046) and age (OR=1.04 [95% CI=0.88-1.15], P=0.012) were independent factors related to SIRS negativity in septic patients. Analysis with a restricted cubic spline model showed that the odds ratio (OR) of SIRS negativity continued to increase with age, particularly for those over 80 years old (p for nonlinearity=0.024). The odds ratio of SIRS negativity was more than 1 when the SOFA score was less than 4 (p for nonlinearity=0.261). Conclusions: In septic patients with a poor prognosis, elderly individuals (over 80 years old) are more likely to exhibit SIRS negativity during the early stage of sepsis, particularly when they present with mild organ dysfunction (SOFA score less than 4). Neither comorbidities nor BMI was related to SIRS negativity in septic patients with a poor prognosis.

Background:Liver transplantation (LT) has been recognized as the most effective therapy for end-stage liver disease (ESLD). However, the question of whether LT can improve erectile function in patients with ESLD remains controversial. Therefore, we conducted this meta-analysis to evaluate the association between LT and erectile dysfunction (ED). Methods:According to the PRISMA guidelines, studies were included after conducting searches in four databases from March 2024 onwards. These databases included PubMed, Cochrane Library, Web of Science, and Embase. The primary outcome of interest was to compare the International Index of Erectile Function (IIEF) scores between patients after and before LT. Standardized mean differences (SMDs) and their corresponding 95% confidence intervals (CIs) were utilized to assess the relationship between LT and ED. Results:The results showed that the LT group had higher IIEF-5 domain scores for erectile function compared to the control group (SMD =-0.31, 95% CI: -0.53 to -0.09), P=0.007). No heterogeneity or publication bias was detected in the results. Additionally, the IIEF-15 domain score was also found to be improved after LT. Specifically, the LT group had higher domain scores for erectile function (SMD =-0.77, 95% CI: -1.07 to -0.48, P<0.001), orgasmic function (SMD =-0.82, 95% CI: -1.12 to -0.52, P<0.001), sexual desire (SMD =-0.89, 95% CI: -1.19 to -0.59, P<0.001), intercourse satisfaction (SMD =-0.92, 95% CI: -1.22 to -0.62, P<0.001), and overall satisfaction (SMD =-0.87, 95% CI: -1.17 to -0.57, P<0.001). Conclusions:It is suggested by our meta-analysis that LT may contribute to improvements in erectile function among men with ESLD. This improvement may be related to the remarkable improvement in endocrine hormone disorders observed after LT. However, future studies with better designs and larger sample sizes are still needed to confirm our conclusions. Additionally, attention to erectile function before and after surgery in patients with liver failure is crucial.

Background Despite the very high sensitivity of the Systemic Inflammatory Response Syndrome (SIRS) score for identifying sepsis, there remains a subset of septic patients who exhibit negative SIRS scores, and unfortunately, many of these patients experience poor outcomes. This study aims to investigate the factors associated with SIRS negativity during the early stage of sepsis in deceased septic patients. Methods Adult septic patients were included from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database between 2008 and 2019. Sepsis was determined based on the Sepsis 3.0 criteria. Patients who did not survive after 28 days were assigned to the SIRS-negative or SIRS-positive group according to whether the SIRS score was less than two points within 24 hours of intensive care unit (ICU) admission. The baseline data of patients in the SIRS-negative and SIRS-positive groups were collected and compared. The factors associated with SIRS negativity in septic patients were analysed by logistic regression. The dose-response relationships of SIRS negativity with SOFA score and age were determined with a restricted cubic spline model. Results A total of 53,150 patients were screened in the MIMIC-IV database, and 2706 sepsis nonsurvivors were ultimately included, 101 of whom were negative for SIRS. There were significant differences in SOFA scores between groups (8.18 ± 3.58 vs. 9.75 ± 4.28, P < 0.001). In addition, differences in several other parameters nearly reached statistical significance, including age (76 [61 to 86] vs. 72 [60 to 82], P = 0.053), body mass index (BMI) (26 [22 to 31] vs. 27 [24 to 32], P = 0.056), and the Charlson comorbidity index (8 [6 to 9] vs. 7 [5 to 9], P = 0.052). Logistic regression analysis indicated that both SOFA score (OR = 0.93 [95% CI = 0.87-1.00], P = 0.046) and age (OR = 1.04 [95% CI = 0.88–1.15], P = 0.012) were independent factors related to SIRS negativity in septic patients. Analysis with a restricted cubic spline model showed that the odds ratio (OR) of SIRS negativity continued to increase with age, particularly for those over 80 years old (p for nonlinearity = 0.024). The odds ratio of SIRS negativity was more than 1 when the SOFA score was less than 4 (p for nonlinearity = 0.261). Conclusions For sepsis patients with poor prognoses, elderly individuals (over 80 years) are more likely to be SIRS negative when they have mild organ dysfunction damage (less than 4 SOFA scores) in the early stage of sepsis. This warranted an opportunity to provide early diagnosis for elderly population with negative SIRS score, in order to prevent poor outcomes.

Objectives: This study aims to investigate the factors associated with systemic inflammatory response syndrome (SIRS) negativity during the early stage of sepsis in deceased septic patients. Methods: Adult septic patients were included from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database between 2008 and 2019. Patients who did not survive after 28 days were assigned to the SIRS-negative or SIRS-positive group according to whether the SIRS score was less than two points within 24 h of intensive care unit admission. Logistic regression and a restricted cubic spline model were used to analyze factors and dose-response relationships. Results: A total of 53,150 patients were screened in the MIMIC-IV database, and 2706 sepsis nonsurvivors were ultimately included, 101 of whom were negative for SIRS. There were significant differences in sequential organ failure assessment (SOFA) scores between groups (8.18 3.58 vs. 9.75 +/- 4.28, p < 0.001). Logistic regression analysis indicated that lactate (odds ratio [OR] = 0.75 [95% CI = 0.62-0.90], p = 0.002), SOFA score (OR = 0.93 [95% CI = 0.87-1.00], p = 0.046), and age (OR = 1.04 [95% CI = 0.88-1.15], p = 0.012) were independent factors related to SIRS negativity in septic patients. Analysis with a restricted cubic spline model showed that the OR of SIRS negativity continued to increase with age, particularly for those over 80 years old (p for nonlinearity = 0.024). The OR of SIRS negativity was more than 1 when the SOFA score was <4 (p for nonlinearity = 0.149) and when the lactate was <1 (p for nonlinearity = 0.014). Conclusions: For sepsis patients with poor prognoses, elderly individuals are more likely to be SIRS negative when they have mild organ dysfunction damage or mild tissue hypoperfusion in the early stage of sepsis. This warranted an opportunity to provide early diagnosis for elderly population with negative SIRS score in order to prevent poor outcomes.

Objective: To explore patients' knowledge, attitude, and practice (KAP) toward varicocele in China and the relationship between treatment selection and KAP. Methods: This cross-sectional study enrolled varicocele patients at the Third Affiliated Hospital of Soochow University (September to October 2023). Structural equation modeling (SEM) was used to explore the relationship between clinical factors and KAP. A score >mean score for each dimension was defined as adequate knowledge, positive attitude, and proactive practice. The patients were grouped according to varicocelectomy vs no surgery. Univariable and multivariable logistic regression analyses were used to identify the factors independently associated with KAP. A structural equation modeling (SEM) analysis was performed to examine how the KAP dimensions influenced each other. Results: Among 502 patients, 44.02%, 35.86%, and 20.12% were <= 30, 31-40, and >40 years old, respectively. Those who underwent varicocelectomy (n=407) had significantly higher knowledge (20 (15-22) vs 0 (0-6), P<0.001), attitude (26 (24-26) vs 14 (10-18), P<0.001), and practice (20 (17-24) vs 8 (6-16), P<0.001) than those who did not. A higher proportion of patients with varicocelectomy were <40 years old, more educated, had higher income, and were unmarried compared with those without surgery (all P<0.001). High school or higher education level and varicocelectomy (irrespective of type) were independently associated with adequate knowledge (all P<0.001). Knowledge, college/bachelor's degree education, and varicocelectomy type (irrespective of type) were associated with positive attitudes (all P<0.05). In the SEM, knowledge directly influenced attitude, knowledge directly influenced practice, and attitude directly influenced practice (all P<0.001). Having knowledge of the subject may direct varicocele patients to varicocelectomy. Conclusion: Chinese patients who underwent varicocelectomy exhibit appropriate KAP regarding varicocele, while non-surgery patients have poorer KAP. These results suggest that patients who did not undergo surgery should nevertheless be properly informed about their disease.

In recent years, extracellular vesicles (EVs) have gained significant attention due to their tremendous potential for clinical applications. EVs play a crucial role in various aspects, including tumorigenesis, drug resistance, immune escape, and reconstruction of the tumor microenvironment. Despite the growing interest in EVs, many questions still need to be addressed before they can be practically applied in clinical settings. This paper aims to review EVs' isolation methods, structure research, the roles of EVs in tumorigenesis and their mechanisms in multiple types of tumors, their potential application in drug delivery, and the expectations for their future in clinical research.

Tumors of the male genitourinary system are of great concern to the health of men worldwide. Although emerging experiment-based evidence indicates an association between hepcidin and such cancers, an integrated analysis is still lacking. For this reason, in this study, we determined the underlying oncogenic functions of hepcidin in common male genitourinary system tumors, including bladder urothelial carcinoma (BLCA), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), prostate adenocarcinoma (PRAD), and testicular germ cell tumors (TGCT) according to the data from The Cancer Genome Atlas. We found that hepcidin was highly expressed in kidney and testicular cancers. Meanwhile, the expression level of hepcidin was distinctly associated with the prognosis and immune cell infiltration in male patients with certain genitourinary system cancers, especially in KIRC. Elevated hepcidin levels also present as a risk factor in male genitourinary system tumors. Moreover, enrichment analyses revealed that some of the principal associated signaling pathways involving hepcidin and its related genes are identified as tumorigenesis-related. Immunofluorescence staining confirmed the conclusion of our immune infiltration analysis in KIRC tissue. In this study, for the first time, we provided evidence for the oncogenic function of hepcidin in different types of male genitourinary system tumors.

Background: Hypoxia is widespread in solid tumors and is directly associated with colorectal cancer (CRC) aggressiveness, poor prognosis, and immunotherapy resistance. In this study, we aimed at developing a hypoxia-related marker to improve the prognosis prediction in CRC.Methods: We used gene expression data of CRC samples from the Cancer Genome Atlas Database and the hypoxia gene set to obtain a hypoxia gene expression matrice of 479 CRC patients. The prognostic model was constructed by screening hypoxia risk genes that were significantly associated with prognosis by univariate and multivariate Cox regression analysis. The predictive performance of the prognostic model was evaluated by Kaplan-Meier survival curve analyses and ROC curve analysis and validated in the GSE17536 dataset of Gene Expression Omnibus database. Finally, we analyzed the immune cell infiltration and expression of immunosuppressive genes in CRC patients at high and low risk of hypoxia.Results: We constructed a hypoxia risk prognostic model composed of two hypoxia-related genes ( SLC2A3 and ENO3 ), which was proved to have better sensitivity and specificity after a series of validation. Independent prognostic analysis revealed that the risk score can serve as an independent prognostic factor for CRC. The infiltration of natural killer resting cells, activated master cells and T-cell regulatory cells were significantly increased in the hypoxia high-risk group, and Gene Set Enrichment Analysis showed that gene sets involved in tumor proliferation and differentiation, immune tolerance as well as hypoxia were also significantly enriched in this group. Negatively regulated genes in the Cancer Immunity Cycle, as well as immune checkpoints, were upregulated in the high hypoxia risk group, forming an immunosuppressive microenvironment, and mediating the immune escape. Conclusions: In summary, we constructed and validated a reliable hypoxia risk model that can independently predict the prognosis of CRC patients and reflect the status of the immune microenvironment, which is beneficial for screening CRC prognostic biomarkers and therapeutic targets.

Background: Patients with advanced clear cell renal cell carcinoma (ccRCC) have a poor prognosis and lack effective prognostic biomarkers. N6-methyladenosine-related lncRNAs (m6A-related long noncoding RNAs [lncRNAs]) have been confirmed to be associated with the development of multiple tumors, but its role in ccRCC is not clear. Methods: Gene expression data and clinical information of ccRCC patients were extracted from The Cancer Genome Atlas Database. The prognostic m6A-related lncRNAs were obtained by Pearson's correlation analysis and univariate Cox regression analysis. Afterward, the cluster classification and its correlation with prognosis, clinical characteristics, and immunity were analyzed. LASSO regression was used to establish the prognostic risk model. The predictive performance of the prognostic model was evaluated and validated by survival analysis and receiver operating characteristic curve analysis, et al. The expression of immune checkpoints and immune cell infiltration in patients with different risks were systematically analyzed. Results: A total of 27 prognostic m6A-related lncRNAs were identified. These m6A-related lncRNAs were differentially expressed between tumor and normal tissues. Among them, 24 high-risk m6A-related lncRNAs were overexpressed in Cluster 2 and correlated with poor prognosis, low stromal score, high expression of immune checkpoints, and immunosuppressive cells infiltration. Based upon, a prognostic risk model composed of seven m6A-related lncRNAs was constructed. After a series of analyses, it was proved that this model had good sensitivity and specificity, and could predict the prognosis of patients with different clinical stratification. The expression of PD-1, PD-L1, CTLA-4, LAG-3, TIM-3, and TIGIT were significantly increased in the high-risk patients, and there was a correlation between the risk score and immune cell infiltration. Conclusions: The seven m6A-related lncRNAs prognostic risk signature showed reliable prognostic predictive power for ccRCC and was associated with the expression of immune checkpoints and immune cell infiltration. This seven m6A-related lncRNAs signature will be helpful in managing ccRCC and guiding individualized immunotherapy.

Background: Patients with advanced clear cell renal cell carcinoma (ccRCC) have a poor prognosis and lack effective prognostic biomarkers. This study uses bioinformatics analysis to identify N6-methyladenosine-related lncRNAs (m6A-related lncRNAs) as new prognostic biomarkers for ccRCC. Methods: Gene expression data and related clinical information of ccRCC patients were extracted from the Cancer Genome Atlas Database. m6A-related lncRNAs were obtained by co-expression analysis. Univariate Cox regression analysis was performed on these lncRNAs to find the prognostic-related m6A-related lncRNAs, and consensus clustering analysis was performed. The prognostic signature was screened by LASSO regression and a prognostic model was constructed. The predictive performance of the prognostic model was evaluated and validated by survival analysis and ROC curve analysis, etc. In addition, we also systematically analyzed the expression of immune checkpoints and immune cell infiltration in ccRCC patients. Results : First, 27 m6A-related lncRNAs associated with prognosis were identified, which were significantly differentially expressed between tumor and normal tissues. Consensus clustering analysis indicated that cluster 2 was associated with poor prognosis, low stromal score, high expression of PD-1, PD-L1, CTLA-4, LAG-3, TIM-3, TIGIT , and immunosuppressive cell infiltration. The signaling pathways related to tumor progression, drug resistance, and angiogenesis and biological processes related to protein methylation and phosphatidic acid metabolism are significantly enriched in cluster 2. Subsequently, LASSO regression analysis was used to construct a prognostic risk model based on 7 m6A-related lncRNAs signature , which can be used as an independent prognostic indicator. After a series of analyses, it was shown that this model had good sensitivity and specificity, can predict the prognosis of patients with different clinical stratifications and was associated with the progression of ccRCC. The expression levels of immune checkpoints were significantly increased in high-risk patients, and there was a certain correlation between the risk score and immune cell infiltration. Conclusions: In summary, we constructed and validated a risk model that can independently predict the prognosis of ccRCC patients and reflect the immune microenvironment based on m6A-related lncRNAs; the model is conducive to the screening of biomarkers of ccRCC prognosis and may have the potential to reflect the response of ccRCCs to immunotherapy.

Background Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent cancers in renal cancer patients. Currently, mTOR and vascular endothelial growth factor (VEGF) inhibitors are the main targets of clinical drugs used to treat ccRCC. However, the major clinical challenge with these treatments is drug resistance. So far, the mechanisms of drug resistance in cancer are not fully understood. Methods We applied tumor-derived exosomes to treat renal cells to detect the survival rate after co-treated with anti-tumor drugs—TNFα, mammalian target of rapamycin (mTOR) inhibitor or STAT3 inhibitor. Meanwhile, we also detected the expression change in the protein level related to the proliferation and exosome secretion. Results Exosomes derived from renal carcinoma cells facilitate resistance in tumors cells when given drug therapy via the mTOR-ERK-STAT-NF-κB signaling pathway. Conclusions Our results provide new insights on tumor cells resistance to drug therapies in general, and that exosomes could be the potential targets in treatment of ccRCC in future clinical therapy.

Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a rare and polymorphic tumor, which has been previously considered to be a low-grade malignancy, predominantly occurring in women. To the best of our knowledge, MTSCC with bladder metastasis has never been reported. The current study presents five adult cases of MTSCC that included three male and two female patients. Among the male cases, two were of advanced stage, one with MTSCC and renal chromophobe cell carcinoma with bladder metastasis and the other with MTSCC with invasion of the renal vein. The other three cases with small masses were at an early stage. All five cases had a good prognosis and were without recurrence after several years of follow-up. A 70-year-old male with intermittent gross hematuria, intermittent renal colic, and groin radiation pain for a year (case 1), was incidentally detected to have a left renal density mass by total abdominal enhanced computed tomography scans. In the other four cases, renal masses were found by B-ultrasound. The patient in case 1 underwent a retroperitoneal laparoscopic radical nephroureterectomy with bladder cuff resection and transurethral resection of the bladder tumor, and received gemcitabine hydrochloride via intravesical instillation therapy plus cisplatin chemotherapy every 3 months. The patient in case 2 underwent an open left radical nephrectomy and renal pedicle lymph node dissection. The other three patients underwent a laparoscopic radical nephrectomy. All five patients had no recurrence or new metastasis in other organs after follow-up. In conclusion, the incidence of MTSCC in men and women is not as disparate as reported in previous publications. The characteristics of the images of the five adult cases in the present study showed a considerable consistency, with only minor differences. The malignancy and prognosis of MTSCC are still controversial, and thus inclusion and review of more cases is required to reach a definite final conclusion. Sunitinib and gemcitabine chemotherapy in combination with cisplatin may be effective for the therapy of MTSCC patients with metastasis, but a larger range of treatments needs to be identified.