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BackgroundWith the development of lifestyle, elevated uric acid and hyperuricemia have become important factors affecting human health, but the biological mechanism and risk factors are still unclear.MethodsA multi-stage, cross-sectional study of 41,136 adults from the NHANES 2003-2018 was conducted. Serum uric acid concentrations, platelet, neutrophil, lymphocyte, and monocyte counts were measured. The systemic inflammation response (SIRI) index and systemic immune-inflammatory (SII) index were calculated to reflect systemic inflammation and systemic immune inflammation. The height and weight data were obtained to assess body mass index (BMI). Generalized linear models were used to examine the relationships of SIRI and SII with uric acid and hyperuricemia risk, as well as the associations of SIRI and SII with BMI, and BMI with uric acid and hyperuricemia risk. Causal mediation effect model was used to assess the mediating effect of BMI in the relationships of SIRI, and SII with uric acid concentration and hyperuricemia risk.ResultsThe prevalence of hyperuricemia in US adults is 19.78%. Positive associations were found in the relationships of SIRI and SII with uric acid level, hyperuricemia risk, and BMI, as well as the relationships of BMI with uric acid and hyperuricemia risk. Causal mediation effect model showed that BMI played an important mediating role in the relationships of SIRI, and SII with uric acid concentration and hyperuricemia risk, with the proportion of mediating effect ranging from 23.0% to 35.9%.ConclusionExposure to higher SIRI and SII is associated with increased uric acid concentration and hyperuricemia risk in adults, and BMI plays an important mediating effect. Reducing systemic inflammation and systemic immune inflammation and proper weight control could be effective ways to reduce hyperuricemia prevalence and related health problems.

Background: Radiotherapy (RT) for breast cancer (BC) may raise the risk of second primary cancers (SPCs), a relationship inadequately studied. Methods: We analyzed 248268 female BC patients from 9 SEER registries, 1988–2018, identifying SPCs >5 years after initial treatment, comparing SPC risks between RT and non-RT cohorts using Fine-Gray and Poisson regressions. Results: Of all participants, 55.4 % received surgery and RT. The RT group had a higher SPC incidence, with excess incidence significantly dropped from 6.9 % in 1990 to 0.2 % in 2012. The 30-year SPC incidence was 24.69 % in the RT cohort and 18.11 % in the NRT cohort. RT increased the risk of SPCs(HR, 1.29 [95%CI,1.26–1.33]; P

Purpose Although several reviews have evaluated the use of PDE5 inhibitors (PDE5i) for treating erectile dysfunction (ED), their specific use in middle-aged and old patients has not been fully evaluated. Given that elderly patients with ED often have a complex combination of systemic and sexual health risk factors, the safety and efficacy of PDE5i in such a context are hereby reviewed.Materials and methods A thorough examination of existing literature has been conducted on PubMed.Results PDE5i has good safety and efficacy, but the situation is more complex for patients with hypogonadism than those with normal testosterone levels, with reduced responsiveness to PDE5i. In this case, combination therapy with testosterone is recommended, safe and effectiveConclusions Eliminating or reducing reversible risk factors and controlling or slowing the development of irreversible factors is an important foundation for using PDE5i to treat ED in all patients, especially middle-aged and elderly ones.

Abstract PDL1 blockade therapy holds great promise in cancer immunotherapy. Ultrasound imaging of PDL1 expression in the tumor is of great importance in predicting the therapeutic efficacy. As a proof‐of‐concept study, a novel ultrasound contrast agent has been innovated here to image and block PDL1 in the tumor tissue. Briefly, extracellular vesicles (EVs) are engineered to display truncated PD1 (tPD1) on the surface to bind PDL1 with high affinity by fusion to EV‐abundant transmembrane protein PTGFRN. The engineered EVs are then encapsulated with Ca(HCO3)2 via electroporation and designated as Gp‐EVtPD1, which would recognize PDL1 highly expressed cells and produce gas in the endosomes and lysosomes. On the one hand, the echogenic signal intensity correlates well with the PDL1 expression and immune response inhibition in the tumor. On the other hand, during the trajectory of Gp‐EVtPD1 in the recipient cells, tPD1 on the EV binds PDL1 and triggers the PDL1 endocytosis and degradation in endosomes/lysosomes in a sequential manner, and thus boosts the anti‐tumor immunity of cytotoxic T cells. In summary, Gp‐EVtPD1 serves as a novel ultrasound contrast agent and blocker of PDL1, which might be of great advantage in imaging PDL1 expression and conquering immune checkpoint blocker resistance.

The choice of coping style of recruits under psychological stress in the process of military task execution has been an important topic in the promotion of military operations and cohesion of military forces. Taking a positive coping style under psychological stress can help recruits overcome the negative effects of stress and improve military morale and group combat effectiveness. Although soldiers' psychological stress in the process of military mission execution having an impact on coping style has been studied by a large body of literature, very little literature has focused on the mechanism of self-efficacy and social support between recruits' psychological stress and coping style from the person-environment fit perspective. Therefore, this study was conducted to analyze the impact of recruits' psychological stress on coping style through a chain mediation model and to discuss the role of self-efficacy and social support in this relationship. Two waves of survey data were utilized to test the research hypotheses on a sample of 1028 Chinese recruits performing military tasks. The results indicated that recruits' psychological stress negatively impacted positive coping styles and positively correlated with negative ones. In addition, self-efficacy and social support mediated the relationship between psychological stress and positive coping style, and self-efficacy mediated the relationship between psychological stress and negative coping style. More importantly, self-efficacy and social support play the chain mediating effect between psychological stress and positive coping style.

Warburg effect is a pivotal hallmark of cancers and appears prevalently in renal cell carcinoma (RCC). FBP1 plays a negative role in Warburg effect as a rate-limiting enzyme in gluconeogenesis, yet its mechanism in RCC remains to be further characterized. Herein, we revealed that FBP1 was downregulated in RCC tissue samples and was related to the poor survival rate of RCC. Strikingly, miR-24-1 whose DNA locus is overlapped with enhancer region chr9:95084940-95087024 was closely linked with the depletion of FBP1 in RCC. Of note, miRNAs like miR-24-1 whose DNA loci are enriched with H3K27ac and H3K4me1 modifications are belonging to nuclear activating miRNAs (NamiRNAs), which surprisingly upregulate target genes in RCC through enhancer beyond the conventional role of repressing target gene expression. Moreover, miR-24-1 reactivated the expression of FBP1 to suppress Warburg effect in RCC cells, and subsequently inhibited proliferation and metastasis of RCC cells. In mechanism, the activating role of miR-24-1 was dependent on enhancer integrity by dual luciferase reporter assay and CRISPR/Cas9 system. Ultimately, animal assay in vivo validated the suppressive function of FBP1 on 786-O and ACHN cells. Collectively, the current study highlighted that activation of FBP1 by enhancer-overlapped miR-24-1 is capable of contributing to Warburg effect repression through which RCC progression is robustly blocked, providing an alternative mechanism for RCC development and as well implying a potential clue for RCC treatment strategy.

BackgroundAlthough erectile dysfunction (ED) often occurs simultaneously with depression, not all patients with ED suffer major depression (MD), with a PHQ-9 score ≥15 indicating MD. Because the PHQ-9 questionnaire includes phrases such as “I think I am a loser” and “I want to commit suicide,” the psychological burdens of ED patients are likely to increase inevitably after using the PHQ-9, which, in turn, may affect ED therapeutic effects. Accordingly, we endeavored to develop a nomogram to predict individual risk of PHQ-9 score ≥15 in these patients.MethodsThe data of 1,142 patients with ED diagnosed in Xijing Hospital and Northwest Women and Children's Hospital from January 2017 to May 2020 were analyzed. While the Least Absolute Shrinkage and Selection Operator regression was employed to screen PHQ-9 score ≥15 related risk factors, multivariate logistic regression analysis was performed to verify these factors and construct the nomogram. The training cohort and an independent cohort that comprised 877 prospectively enrolled patients were used to demonstrate the efficacy of the nomogram.ResultsThe IIEF-5 score, PEDT score, physical pain score, frequent urination, and feeling of endless urination were found to be independent factors of PHQ-9 score ≥15 in patients with ED. The nomogram developed by these five factors showed good calibration and discrimination in internal and external validation, with a predictive accuracy of 0.757 and 0.722, respectively. The sensitivity and specificity of the nomogram in the training cohort were 0.86 and 0.52, respectively. Besides, the sensitivity and specificity of the nomogram in the validation cohort were 0.73 and 0.62, respectively. Moreover, based on the nomogram, the sample was divided into low-risk and high-risk groups.ConclusionThis study established a nomogram to predict individual risk of PHQ-9 score ≥15 in patients with ED. It is deemed that the nomogram may be employed initially to avoid those with a low risk of MD completing questionnaires unnecessarily.

Background and ObjectivesTo establish a prognostic stratification nomogram for T1–2 breast cancer with 1–3 positive lymph nodes to determine which patients can benefit from postmastectomy radiotherapy (PMRT).MethodsA population-based study was conducted utilizing data collected from the Surveillance, Epidemiology, and End Results database. Chi-square test or Fisher exact test was used to compare the distribution of characteristics. Cox analysis identified significant prognostic factors for survival. A prognostic stratification model was constructed by R software. Propensity score matching was applied to balance characteristics between PMRT cohort and control cohort. Kaplan-Meier method was performed to evaluate the performance of stratification and the benefits of PMRT in the total population and three risk groups.ResultsThe overall performance of the nomogram was good (3-year, 5-year, 10-year AUC were 0.75, 0.72 and 0.67, respectively). The nomogram was performed to excellently distinguish low-risk, moderate-risk, and high-risk groups with 10-year overall survival (OS) of 86.9%, 73.7%, and 62.7%, respectively (P

Background: Factors influencing recovery after decompression surgery for cauda equina syndrome (CES) are not completely identified. The authors aimed to investigate the most valuable predictors (MVPs) of poor postoperative recovery (PPR) in patients with CES and construct a nomogram for discerning those who will experience PPR. Methods: Three hundred fifty-six patients with CES secondary to lumbar degenerative diseases treated at Xijing Hospital were randomly divided into training (N= 238) and validation (N=118) cohorts at a 2:1 ratio. Moreover, 92 patients from the 970th Hospital composed the testing cohort. Least Absolute Shrinkage and Selection Operator regression (LASSO) was used for selecting MVPs. The nomogram was developed by integrating coefficients of MVPs in the logistic regression, and its discrimination, calibration, and clinical utility were validated in all three cohorts. Results: After 3 to 5 years of follow-up, the residual rates of bladder dysfunction, bowel dysfunction, sexual dysfunction, and saddle anesthesia were 41.9, 44.1, 63.7, and 29.0%, respectively. MVPs included stress urinary incontinence, overactive bladder, low stream, difficult defecation, fecal incontinence, and saddle anesthesia in order. The discriminatory ability of the nomogram was up to 0.896, 0.919, and 0.848 in the training, validation, and testing cohorts, respectively. Besides, the nomogram showed good calibration and clinical utility in all cohorts. Furthermore, the optimal cutoff value of the nomogram score for distinguishing those who will experience PPR was 148.02, above which postoperative outcomes tend to be poor. Conclusion: The first pretreatment nomogram for discerning CES patients who will experience PPR was developed and validated, which will aid clinicians in clinical decision-making. [ABSTRACT FROM AUTHOR]

Warburg effect is a pivotal hallmark of cancers and appears prevalently in renal cell carcinoma (RCC). FBP1 plays a negative role in Warburg effect as a ratelimiting enzyme in gluconeogenesis, yet its mechanism in RCC remains to be further characterized. Herein, we revealed that FBP1 was downregulated in RCC tissue samples and was related to the poor survival rate of RCC. Strikingly, miR-24-1 whose DNA locus is overlapped with enhancer region chr9:95084940-95087024 was closely linked with the depletion of FBP1 in RCC. Of note, miRNAs like miR-24-1 whose DNA loci are enriched with H3K27ac and H3K4me1 modifications are belonging to nuclear activating miRNAs (NamiRNAs), which surprisingly upregulate target genes in RCC through enhancer beyond the conventional role of repressing target gene expression. Moreover, miR-24-1 reactivated the expression of FBP1 to suppress Warburg effect in RCC cells, and subsequently inhibited proliferation and metastasis of RCC cells. In mechanism, the activating role of miR-24-1 was dependent on enhancer integrity by dual luciferase reporter assay and CRISPR/Cas9 system. Ultimately, animal assay in vivo validated the suppressive function of FBP1 on 786-O and ACHN cells. Collectively, the current study highlighted that activation of FBP1 by enhancer-overlapped miR-24-1 is capable of contributing to Warburg effect repression through which RCC progression is robustly blocked, providing an alternative mechanism for RCC development and as well implying a potential clue for RCC treatment strategy. [ABSTRACT FROM AUTHOR]

Objectives: To carry out a real-life retrospective, multicenter survey on the prevalence, subtype, and proposed treatments of premature ejaculation in China. Methods: Real-life data were provided by 8 major Centers from China, selected as active in basic and clinical research on PE and participating to international meetings of sexual medicine and andrology. Centers provided a filled survey containing relevant information concerning PE prevalence, pathogenesis and treatment. Results: In 2019, among 156,486 patients coming to the centers, 32,667 visits having PE as the chief complaint were performed (20.9%). Almost all patients received treatment prescriptions (32,641 patients, 99.92%); 23,273 patients came back for a follow-up visit in the subsequent 12 months (71.2% of those who initially received treatment). Dapoxetine, either alone or in combination with another therapy, was the most prevalent treatment, prescribed to 22,767 patients (69.7% of treated patients), followed by Traditional Chinese medicine (TCM) (39.4%). At follow-up, 8174 patients were unsatisfied with treatment, and a new treatment was proposed (35.12%). Dapoxetine was the best treatment, with an overall 27.1% switching rate when used either alone or in combination: while the switching rate for Dapoxetine alone was 44.2%, the association of the same drug with psychotherapy resulted in much lower rates (19.5%) and reached a minimum of 12% when also combined with TCM demonstrating how cultural aspects and medical attitudes may dramatically impact on the therapy of a multifaceted, complex, and culture-grounded sexual symptom such as PE. Conclusions: Taking switching rates as surrogate markers of treatment failure, this real-life study – the largest in the field - shows that in a more patient-oriented (as in Chinese medical culture), and less symptom-oriented (as in Western medical attitudes), Dapoxetine is a successful treatment for PE patients, with higher reliability when used alone or as part of combined and integrated therapies. Conflicts of Interest: EAJ is or has been a speaker and/or paid consultant for Bayer, Ibsa, Lundbeck, Menarini, Merk-Serono, Otsuka, Pfizer, Shionogi, and Viatris. AS has been a paid consultant for Menarini. All others declare not to have any competing interest for the present manuscript. [ABSTRACT FROM AUTHOR]